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Admission eosinopenia predicted severe CDI outcomes
For patients with even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.
“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.
In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.
Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.
Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
For patients with even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.
“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.
In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.
Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.
Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
For patients with even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.
“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.
In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.
Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.
Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
FROM JAMA SURGERY
Key clinical point: Undetectable peripheral eosinophils predicted severe outcomes in patients admitted with Clostridium difficile infection.
Major finding: In the training and validation datasets, odds of in-hospital mortality were 2.01 (95% CI, 1.08-3.73) and 2.26 (95% CI, 1.33-3.83), respectively.
Study details: Two-hospital cohort study of 2,065 patients admitted with C. difficile infection.
Disclosures: The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
Source: Kulaylat A et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
Erythematous Verrucous Plaque on the Hand
The Diagnosis: Chromomycosis
Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.
Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.1
Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.2 Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.3 Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.
Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).2 Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.4 Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.5 However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.6
There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.7 In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.8 Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.2
Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.
- Queiroz-Telles F, Esterre P, Perez-Blanco M, et al. Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment. Med Mycol. 2009;47:3-15.
- Krzyściak PM, Pindycka-Piaszczyńska M, Piaszczyński M. Chromoblastomycosis. Postepy Dermatol Allergol. 2014;31:310-321.
- Jayalakshmi P, Looi LM, Soo-Hoo TS. Chromoblastomycosis in Malaysia. Mycopathologica. 1990;109:27-31.
- Zayour M, Lazova R. Pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2011;33:112-126.
- El-Khoury J, Kibbi AG, Abbas O. Mucocutaneous pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2012;34:165-175.
- Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation [published online June 25, 2013]. J Skin Cancer. 2013;2013:752864.
- Queiroz-Telles F, Santos DW. Challenges in the therapy of chromoblastomycosis. Mycopathologia. 2013;175:477-488.
- Queiroz-Telles F, de Hoog S, Santos DW, et al. Chromoblastomycosis. Clin Microbiol Rev. 2017;30:233-276.
The Diagnosis: Chromomycosis
Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.
Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.1
Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.2 Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.3 Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.
Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).2 Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.4 Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.5 However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.6
There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.7 In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.8 Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.2
Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.
The Diagnosis: Chromomycosis
Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.
Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.1
Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.2 Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.3 Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.
Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).2 Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.4 Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.5 However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.6
There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.7 In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.8 Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.2
Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.
- Queiroz-Telles F, Esterre P, Perez-Blanco M, et al. Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment. Med Mycol. 2009;47:3-15.
- Krzyściak PM, Pindycka-Piaszczyńska M, Piaszczyński M. Chromoblastomycosis. Postepy Dermatol Allergol. 2014;31:310-321.
- Jayalakshmi P, Looi LM, Soo-Hoo TS. Chromoblastomycosis in Malaysia. Mycopathologica. 1990;109:27-31.
- Zayour M, Lazova R. Pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2011;33:112-126.
- El-Khoury J, Kibbi AG, Abbas O. Mucocutaneous pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2012;34:165-175.
- Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation [published online June 25, 2013]. J Skin Cancer. 2013;2013:752864.
- Queiroz-Telles F, Santos DW. Challenges in the therapy of chromoblastomycosis. Mycopathologia. 2013;175:477-488.
- Queiroz-Telles F, de Hoog S, Santos DW, et al. Chromoblastomycosis. Clin Microbiol Rev. 2017;30:233-276.
- Queiroz-Telles F, Esterre P, Perez-Blanco M, et al. Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment. Med Mycol. 2009;47:3-15.
- Krzyściak PM, Pindycka-Piaszczyńska M, Piaszczyński M. Chromoblastomycosis. Postepy Dermatol Allergol. 2014;31:310-321.
- Jayalakshmi P, Looi LM, Soo-Hoo TS. Chromoblastomycosis in Malaysia. Mycopathologica. 1990;109:27-31.
- Zayour M, Lazova R. Pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2011;33:112-126.
- El-Khoury J, Kibbi AG, Abbas O. Mucocutaneous pseudoepitheliomatous hyperplasia: a review. Am J Dermatopathol. 2012;34:165-175.
- Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation [published online June 25, 2013]. J Skin Cancer. 2013;2013:752864.
- Queiroz-Telles F, Santos DW. Challenges in the therapy of chromoblastomycosis. Mycopathologia. 2013;175:477-488.
- Queiroz-Telles F, de Hoog S, Santos DW, et al. Chromoblastomycosis. Clin Microbiol Rev. 2017;30:233-276.
A 75-year-old retired farmer presented with an erythematous verrucous plaque on the dorsal aspect of the left hand of 4 years' duration. Superficial biopsies from the lesion 4 years prior to presentation revealed pseudoepitheliomatous hyperplasia suggestive of squamous cell carcinoma, which led to the excision of the lesion along with 2 digits of the left hand. Despite surgery, the lesions promptly recurred and continued to progress. Physical examination revealed a verrucous plaque with crusting and small ulcerations (black dots) over the extensor aspect of the left hand and forearm.
ID experts urge widespread flu vaccination for 2018-2019 season
WASHINGTON – The flu vaccine may not be perfect, but it can reduce the severity of illness and curb the risk of spreading the disease to others, William Schaffner, MD, emphasized at a press conference held by the National Foundation for Infectious Diseases.
“Give the vaccine credit for softening the blow,” said Dr. Schaffner, medical director of NFID and a professor at Vanderbilt University in Nashville.
Dr. Schaffner and a panel of experts including U.S. Surgeon General Jerome M. Adams, MD, encouraged the public and the health care community to follow recommendation from the Centers for Disease Control & Prevention that everyone aged 6 months and older receive an influenza vaccine.
Dr. Schaffner shared recent data showing that complications from the flu don’t stop when the acute illness resolves. Acute influenza causes a whole-body inflammatory reaction, and consequently “there is an increased risk of heart attack and stroke during the 2-4 weeks of recovery from acute influenza,” he said. In addition, older adults who experience acute flu and are already frail may never regain their pre-flu level of function, as the flu can start a “domino effect of decline and disability.”
Despite last year’s severe flu season that included 180 deaths in children, vaccination remains the most effective protection against the flu, Dr. Adams said.
This year, between 163 million and 168 million doses of vaccine will be available in the United States. The vaccine is available in a range of settings including doctors’ offices, pharmacies, grocery stores, and workplaces, said Dr. Adams.
Flu vaccine choices this year include a return of the live-attenuated influenza vaccine (LAIV) given via nasal spray, along with the standard influenza vaccine that includes either three influenza viruses (trivalent, with two influenza A and one influenza B) or four influenza viruses (quadrivalent, with two influenza A and two influenza B). Other options are adjuvanted vaccine and high-dose vaccine for adults aged 65 years and older, and a cell-based and recombinant vaccine as alternatives to egg-based vaccines.
Dr. Adams emphasized the importance of healthy people getting vaccinated to protect the community. “All the people who died from the flu caught it from someone else,” he said.
The message to health care providers remains the same: Recommend the flu vaccine to patients at every opportunity, and lead by example and get vaccinated yourself, Dr. Adams said. He noted this year’s strategies to promote flu vaccination on social media, and encouraged clinicians to recommend the flu shot to their patients and to showcase their own shots via the #FightFlu hashtag.
Vaccination among health care personnel last year was approximately 78%, which is a plateau over the past several years (MMWR 2018; 67:1050-54).
Be prepared to offer antivirals to patients as appropriate, and to promote the pneumococcal vaccine to eligible older adults as well, to protect not only themselves, but their contacts and the community, Dr. Adams emphasized. Currently approved antiviral drugs recommended for the 2018-2019 flu season: oseltamivir, zanamivir, and peramivir.
Wendy Sue Swanson, MD, of Seattle Children’s Hospital, stressed the importance of flu vaccination for all children, given their ability to spread viral infections. She noted a concerning 2% drop in vaccinations for children aged 6 months to 4 years, although vaccination coverage in this group was highest among children overall, at approximately 68% last season.
Last year, approximately 80% of the child deaths from flu occurred in unvaccinated children, but the vaccine has been shown to reduce the likelihood of hospitalization or death even if a child does become ill, Dr. Swanson said.
Laura E. Riley, MD, of Weill Cornell Medical Center, noted that vaccination of pregnant women has plateaued in recent years, and was 49% last year. “Our goal is 80% plus,” she said. Data show that pregnant women who received flu vaccination were 40% less likely to be hospitalized for the flu, she noted. The American College of Obstetricians and Gynecologists recommends flu vaccination as safe during any trimester, and valuable to both mothers and newborns because it provides protective antibodies during the first 6 months of life before babies can receive their own vaccinations, Dr. Riley said.
More information about this year’s flu season is available from the CDC and NFID.
WASHINGTON – The flu vaccine may not be perfect, but it can reduce the severity of illness and curb the risk of spreading the disease to others, William Schaffner, MD, emphasized at a press conference held by the National Foundation for Infectious Diseases.
“Give the vaccine credit for softening the blow,” said Dr. Schaffner, medical director of NFID and a professor at Vanderbilt University in Nashville.
Dr. Schaffner and a panel of experts including U.S. Surgeon General Jerome M. Adams, MD, encouraged the public and the health care community to follow recommendation from the Centers for Disease Control & Prevention that everyone aged 6 months and older receive an influenza vaccine.
Dr. Schaffner shared recent data showing that complications from the flu don’t stop when the acute illness resolves. Acute influenza causes a whole-body inflammatory reaction, and consequently “there is an increased risk of heart attack and stroke during the 2-4 weeks of recovery from acute influenza,” he said. In addition, older adults who experience acute flu and are already frail may never regain their pre-flu level of function, as the flu can start a “domino effect of decline and disability.”
Despite last year’s severe flu season that included 180 deaths in children, vaccination remains the most effective protection against the flu, Dr. Adams said.
This year, between 163 million and 168 million doses of vaccine will be available in the United States. The vaccine is available in a range of settings including doctors’ offices, pharmacies, grocery stores, and workplaces, said Dr. Adams.
Flu vaccine choices this year include a return of the live-attenuated influenza vaccine (LAIV) given via nasal spray, along with the standard influenza vaccine that includes either three influenza viruses (trivalent, with two influenza A and one influenza B) or four influenza viruses (quadrivalent, with two influenza A and two influenza B). Other options are adjuvanted vaccine and high-dose vaccine for adults aged 65 years and older, and a cell-based and recombinant vaccine as alternatives to egg-based vaccines.
Dr. Adams emphasized the importance of healthy people getting vaccinated to protect the community. “All the people who died from the flu caught it from someone else,” he said.
The message to health care providers remains the same: Recommend the flu vaccine to patients at every opportunity, and lead by example and get vaccinated yourself, Dr. Adams said. He noted this year’s strategies to promote flu vaccination on social media, and encouraged clinicians to recommend the flu shot to their patients and to showcase their own shots via the #FightFlu hashtag.
Vaccination among health care personnel last year was approximately 78%, which is a plateau over the past several years (MMWR 2018; 67:1050-54).
Be prepared to offer antivirals to patients as appropriate, and to promote the pneumococcal vaccine to eligible older adults as well, to protect not only themselves, but their contacts and the community, Dr. Adams emphasized. Currently approved antiviral drugs recommended for the 2018-2019 flu season: oseltamivir, zanamivir, and peramivir.
Wendy Sue Swanson, MD, of Seattle Children’s Hospital, stressed the importance of flu vaccination for all children, given their ability to spread viral infections. She noted a concerning 2% drop in vaccinations for children aged 6 months to 4 years, although vaccination coverage in this group was highest among children overall, at approximately 68% last season.
Last year, approximately 80% of the child deaths from flu occurred in unvaccinated children, but the vaccine has been shown to reduce the likelihood of hospitalization or death even if a child does become ill, Dr. Swanson said.
Laura E. Riley, MD, of Weill Cornell Medical Center, noted that vaccination of pregnant women has plateaued in recent years, and was 49% last year. “Our goal is 80% plus,” she said. Data show that pregnant women who received flu vaccination were 40% less likely to be hospitalized for the flu, she noted. The American College of Obstetricians and Gynecologists recommends flu vaccination as safe during any trimester, and valuable to both mothers and newborns because it provides protective antibodies during the first 6 months of life before babies can receive their own vaccinations, Dr. Riley said.
More information about this year’s flu season is available from the CDC and NFID.
WASHINGTON – The flu vaccine may not be perfect, but it can reduce the severity of illness and curb the risk of spreading the disease to others, William Schaffner, MD, emphasized at a press conference held by the National Foundation for Infectious Diseases.
“Give the vaccine credit for softening the blow,” said Dr. Schaffner, medical director of NFID and a professor at Vanderbilt University in Nashville.
Dr. Schaffner and a panel of experts including U.S. Surgeon General Jerome M. Adams, MD, encouraged the public and the health care community to follow recommendation from the Centers for Disease Control & Prevention that everyone aged 6 months and older receive an influenza vaccine.
Dr. Schaffner shared recent data showing that complications from the flu don’t stop when the acute illness resolves. Acute influenza causes a whole-body inflammatory reaction, and consequently “there is an increased risk of heart attack and stroke during the 2-4 weeks of recovery from acute influenza,” he said. In addition, older adults who experience acute flu and are already frail may never regain their pre-flu level of function, as the flu can start a “domino effect of decline and disability.”
Despite last year’s severe flu season that included 180 deaths in children, vaccination remains the most effective protection against the flu, Dr. Adams said.
This year, between 163 million and 168 million doses of vaccine will be available in the United States. The vaccine is available in a range of settings including doctors’ offices, pharmacies, grocery stores, and workplaces, said Dr. Adams.
Flu vaccine choices this year include a return of the live-attenuated influenza vaccine (LAIV) given via nasal spray, along with the standard influenza vaccine that includes either three influenza viruses (trivalent, with two influenza A and one influenza B) or four influenza viruses (quadrivalent, with two influenza A and two influenza B). Other options are adjuvanted vaccine and high-dose vaccine for adults aged 65 years and older, and a cell-based and recombinant vaccine as alternatives to egg-based vaccines.
Dr. Adams emphasized the importance of healthy people getting vaccinated to protect the community. “All the people who died from the flu caught it from someone else,” he said.
The message to health care providers remains the same: Recommend the flu vaccine to patients at every opportunity, and lead by example and get vaccinated yourself, Dr. Adams said. He noted this year’s strategies to promote flu vaccination on social media, and encouraged clinicians to recommend the flu shot to their patients and to showcase their own shots via the #FightFlu hashtag.
Vaccination among health care personnel last year was approximately 78%, which is a plateau over the past several years (MMWR 2018; 67:1050-54).
Be prepared to offer antivirals to patients as appropriate, and to promote the pneumococcal vaccine to eligible older adults as well, to protect not only themselves, but their contacts and the community, Dr. Adams emphasized. Currently approved antiviral drugs recommended for the 2018-2019 flu season: oseltamivir, zanamivir, and peramivir.
Wendy Sue Swanson, MD, of Seattle Children’s Hospital, stressed the importance of flu vaccination for all children, given their ability to spread viral infections. She noted a concerning 2% drop in vaccinations for children aged 6 months to 4 years, although vaccination coverage in this group was highest among children overall, at approximately 68% last season.
Last year, approximately 80% of the child deaths from flu occurred in unvaccinated children, but the vaccine has been shown to reduce the likelihood of hospitalization or death even if a child does become ill, Dr. Swanson said.
Laura E. Riley, MD, of Weill Cornell Medical Center, noted that vaccination of pregnant women has plateaued in recent years, and was 49% last year. “Our goal is 80% plus,” she said. Data show that pregnant women who received flu vaccination were 40% less likely to be hospitalized for the flu, she noted. The American College of Obstetricians and Gynecologists recommends flu vaccination as safe during any trimester, and valuable to both mothers and newborns because it provides protective antibodies during the first 6 months of life before babies can receive their own vaccinations, Dr. Riley said.
More information about this year’s flu season is available from the CDC and NFID.
FROM AN NFID PRESS CONFERENCE
Point-of-care test for respiratory viruses lowers antibiotic use
Routine testing in the ED is advocated
PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.
“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.
In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.
“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”
This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).
From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.
Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.
“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.
“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.
Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.
“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.
This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.
“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.
Routine testing in the ED is advocated
Routine testing in the ED is advocated
PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.
“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.
In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.
“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”
This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).
From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.
Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.
“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.
“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.
Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.
“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.
This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.
“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.
PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.
“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.
In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.
“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”
This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).
From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.
Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.
“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.
“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.
Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.
“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.
This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.
“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.
REPORTING FROM THE ERS CONGRESS 2018
Key clinical point:
Major finding: Of patients with a negative chest x-ray and low CRP level, 36% avoided hospital admission due to a positive test for a virus.
Study details: A case series.
Disclosures: Dr. Roy reports no financial relationships relevant to this study.
Arginine deficiency implicated in novel hemorrhagic fever fatality
Deficiency of the amino acid arginine is implicated in the low platelet counts of severe fever with thrombocytopenia syndrome (SFTS), and a measure of global arginine bioavailability had prognostic value for mortality from the causal bunyavirus, according to a metabolomics analysis of serum from SFTS patients.
The new study also reported results from a randomized, controlled trial of intravenous arginine supplementation in SFTS; the 53 patients who received 20 g of arginine once daily had faster viral clearance than the 60 patients who received supportive care only and a placebo infusion (P = .047). Also, SFTS patients who received arginine had quicker resolution of liver transaminase elevations (P = .001).
There was no survival benefit in arginine administration, though the study’s first author, Xiao-Kun Li, MD, and colleagues noted low overall fatality rates in arginine-treated and placebo groups, at 5.7% and 8.3%, respectively.
Severe fever with thrombocytopenia syndrome is caused by a bunyavirus first identified in 2009; SFTS is being seen with increasing frequency in mainland China, Korea, Japan, and the United States. Infection with the virus “is associated with a wide clinical spectrum, with most of the patients having mild disease but more than 10% developing a fatal outcome,” wrote Dr. Li and the other researchers in Science Translational Medicine.
In the case of individuals with SFTS who fare poorly, previous work had implicated a disordered host immune response leading to severe thrombocytopenia with subsequent bleeding and disseminated intravascular coagulation, said Dr. Li and colleagues. The exact pathogenesis of this mechanism had been unknown, however, so the investigators used a metabolomics analysis on serum samples from prospectively observed SFTS patients. “[W]e determined arginine metabolism to be a key pathway that was involved in the interaction between SFTS [virus] and host response,” they wrote.
In a prospective cohort study that used liquid chromatography–tandem mass spectrometry, Dr. Li of the Beijing Institute of Microbiology and Epidemiology and colleagues examined 166 metabolites from 242 clinical samples to perform the metabolomics analysis. Of the SFTS patients in the study, 46 had both acute and convalescent samples that were matched with 46 healthy controls and 46 patients with fever not caused by SFTS. In a separate analysis, a series of samples were drawn from 10 patients who died of SFTS and matched to 10 who survived the infection and 10 healthy controls.
Statistical analyses allowed the investigators to identify metabolomics signatures that were unique for each sample group. Alteration of the arginine metabolism pathway stood out as the most pronounced differentiator in acute SFTS infection and fatality, wrote Dr. Li and coauthors. “By extracting the relative concentrations of arginine-related metabolites along the pathway, we found that arginine RC was significantly reduced in the acute phase of SFTS compared to healthy controls,” they wrote (P less than .001).
Patients who succumbed to SFTS had even lower arginine concentrations than did those who survived; arginine levels climbed during recovery for survivors, but stayed low in serum samples from SFTS fatalities.
There’s a logical mechanism by which arginine could contribute to platelet dysfunction and thrombocytopenia, noted Dr. Li and collaborators: Arginine is a nitric oxide precursor, and this pathway is known to be a potent inhibitor of platelet activation.
Low arginine levels would have the effect of taking the brakes off platelet activation, and the investigators did find increases in platelet-monocyte complexes and platelet apoptosis in SFTS virus infection (P = .007 and P less than .001, respectively), which further suggests “that platelet hyperactivation might contribute to reduced platelet counts in circulation,” they wrote.
Low arginine levels also have the effect of suppressing T-cell activity, and mediators along this pathway were also altered in patients with SFTS, and even more profoundly altered in patients who died of SFTS.
Dr. Li and colleagues probed the metabolomics data to see whether a global arginine bioavailability ratio (GABR), expressed as arginine/(ornithine + citrulline), could be used to prognosticate clinical outcome in SFTS virus infection. After multivariable analysis, they found that decreased GABR was associated with fatality (P = .039). Further, a low GABR early in infection was prognostic of later fatality, with an area under the receiver operating curve (ROC) of 0.713.
In the double-blind, randomized, placebo-controlled trial of arginine supplementation during SFTS, Dr. Li and coinvestigators found that arginine supplementation did not significantly alter most other laboratory values besides liver transaminases. However, blood urea nitrogen concentration was elevated in those who received arginine, and arginine supplementation was also associated with slightly more vomiting. Serum sampling also revealed that platelet activation and T-cell activity were both corrected in patients given arginine, which gives clues to the means by which arginine supplementation might boost host immune response and promote viral clearing and return to homeostasis of clotting pathways.
Limitations of the clinical trial included relatively small sample sizes and the fact that individuals with severe bleeding were excluded from participation in the trial. Also, the study didn’t account for dietary arginine intake, acknowledged Dr. Li and coauthors.
However, the metabolomics and clinical work taken together used state-of-the-art analytic methods and rigorous experimental design to show “the causal relationship between arginine deficiency and platelet deprivation or immunosuppression by SFTSV infection,” wrote Dr. Li and colleagues.
Disturbance in the arginine–nitric oxide pathway is likely “to be a key biochemical pathway that also plays [a] part in other viral hemorrhagic fever,” said the investigators. “The potential of arginine in treating such infectious diseases [with] similar clinical features as SFTS warrants exploration.”
The study was partially funded by a Bayer Investigator Award; Dr. Li and coauthors reported no other conflicts of interest.
SOURCE: Li X-K et al. Sci Transl Med. doi: 10.1126/scitranslmed.aat4162.
Deficiency of the amino acid arginine is implicated in the low platelet counts of severe fever with thrombocytopenia syndrome (SFTS), and a measure of global arginine bioavailability had prognostic value for mortality from the causal bunyavirus, according to a metabolomics analysis of serum from SFTS patients.
The new study also reported results from a randomized, controlled trial of intravenous arginine supplementation in SFTS; the 53 patients who received 20 g of arginine once daily had faster viral clearance than the 60 patients who received supportive care only and a placebo infusion (P = .047). Also, SFTS patients who received arginine had quicker resolution of liver transaminase elevations (P = .001).
There was no survival benefit in arginine administration, though the study’s first author, Xiao-Kun Li, MD, and colleagues noted low overall fatality rates in arginine-treated and placebo groups, at 5.7% and 8.3%, respectively.
Severe fever with thrombocytopenia syndrome is caused by a bunyavirus first identified in 2009; SFTS is being seen with increasing frequency in mainland China, Korea, Japan, and the United States. Infection with the virus “is associated with a wide clinical spectrum, with most of the patients having mild disease but more than 10% developing a fatal outcome,” wrote Dr. Li and the other researchers in Science Translational Medicine.
In the case of individuals with SFTS who fare poorly, previous work had implicated a disordered host immune response leading to severe thrombocytopenia with subsequent bleeding and disseminated intravascular coagulation, said Dr. Li and colleagues. The exact pathogenesis of this mechanism had been unknown, however, so the investigators used a metabolomics analysis on serum samples from prospectively observed SFTS patients. “[W]e determined arginine metabolism to be a key pathway that was involved in the interaction between SFTS [virus] and host response,” they wrote.
In a prospective cohort study that used liquid chromatography–tandem mass spectrometry, Dr. Li of the Beijing Institute of Microbiology and Epidemiology and colleagues examined 166 metabolites from 242 clinical samples to perform the metabolomics analysis. Of the SFTS patients in the study, 46 had both acute and convalescent samples that were matched with 46 healthy controls and 46 patients with fever not caused by SFTS. In a separate analysis, a series of samples were drawn from 10 patients who died of SFTS and matched to 10 who survived the infection and 10 healthy controls.
Statistical analyses allowed the investigators to identify metabolomics signatures that were unique for each sample group. Alteration of the arginine metabolism pathway stood out as the most pronounced differentiator in acute SFTS infection and fatality, wrote Dr. Li and coauthors. “By extracting the relative concentrations of arginine-related metabolites along the pathway, we found that arginine RC was significantly reduced in the acute phase of SFTS compared to healthy controls,” they wrote (P less than .001).
Patients who succumbed to SFTS had even lower arginine concentrations than did those who survived; arginine levels climbed during recovery for survivors, but stayed low in serum samples from SFTS fatalities.
There’s a logical mechanism by which arginine could contribute to platelet dysfunction and thrombocytopenia, noted Dr. Li and collaborators: Arginine is a nitric oxide precursor, and this pathway is known to be a potent inhibitor of platelet activation.
Low arginine levels would have the effect of taking the brakes off platelet activation, and the investigators did find increases in platelet-monocyte complexes and platelet apoptosis in SFTS virus infection (P = .007 and P less than .001, respectively), which further suggests “that platelet hyperactivation might contribute to reduced platelet counts in circulation,” they wrote.
Low arginine levels also have the effect of suppressing T-cell activity, and mediators along this pathway were also altered in patients with SFTS, and even more profoundly altered in patients who died of SFTS.
Dr. Li and colleagues probed the metabolomics data to see whether a global arginine bioavailability ratio (GABR), expressed as arginine/(ornithine + citrulline), could be used to prognosticate clinical outcome in SFTS virus infection. After multivariable analysis, they found that decreased GABR was associated with fatality (P = .039). Further, a low GABR early in infection was prognostic of later fatality, with an area under the receiver operating curve (ROC) of 0.713.
In the double-blind, randomized, placebo-controlled trial of arginine supplementation during SFTS, Dr. Li and coinvestigators found that arginine supplementation did not significantly alter most other laboratory values besides liver transaminases. However, blood urea nitrogen concentration was elevated in those who received arginine, and arginine supplementation was also associated with slightly more vomiting. Serum sampling also revealed that platelet activation and T-cell activity were both corrected in patients given arginine, which gives clues to the means by which arginine supplementation might boost host immune response and promote viral clearing and return to homeostasis of clotting pathways.
Limitations of the clinical trial included relatively small sample sizes and the fact that individuals with severe bleeding were excluded from participation in the trial. Also, the study didn’t account for dietary arginine intake, acknowledged Dr. Li and coauthors.
However, the metabolomics and clinical work taken together used state-of-the-art analytic methods and rigorous experimental design to show “the causal relationship between arginine deficiency and platelet deprivation or immunosuppression by SFTSV infection,” wrote Dr. Li and colleagues.
Disturbance in the arginine–nitric oxide pathway is likely “to be a key biochemical pathway that also plays [a] part in other viral hemorrhagic fever,” said the investigators. “The potential of arginine in treating such infectious diseases [with] similar clinical features as SFTS warrants exploration.”
The study was partially funded by a Bayer Investigator Award; Dr. Li and coauthors reported no other conflicts of interest.
SOURCE: Li X-K et al. Sci Transl Med. doi: 10.1126/scitranslmed.aat4162.
Deficiency of the amino acid arginine is implicated in the low platelet counts of severe fever with thrombocytopenia syndrome (SFTS), and a measure of global arginine bioavailability had prognostic value for mortality from the causal bunyavirus, according to a metabolomics analysis of serum from SFTS patients.
The new study also reported results from a randomized, controlled trial of intravenous arginine supplementation in SFTS; the 53 patients who received 20 g of arginine once daily had faster viral clearance than the 60 patients who received supportive care only and a placebo infusion (P = .047). Also, SFTS patients who received arginine had quicker resolution of liver transaminase elevations (P = .001).
There was no survival benefit in arginine administration, though the study’s first author, Xiao-Kun Li, MD, and colleagues noted low overall fatality rates in arginine-treated and placebo groups, at 5.7% and 8.3%, respectively.
Severe fever with thrombocytopenia syndrome is caused by a bunyavirus first identified in 2009; SFTS is being seen with increasing frequency in mainland China, Korea, Japan, and the United States. Infection with the virus “is associated with a wide clinical spectrum, with most of the patients having mild disease but more than 10% developing a fatal outcome,” wrote Dr. Li and the other researchers in Science Translational Medicine.
In the case of individuals with SFTS who fare poorly, previous work had implicated a disordered host immune response leading to severe thrombocytopenia with subsequent bleeding and disseminated intravascular coagulation, said Dr. Li and colleagues. The exact pathogenesis of this mechanism had been unknown, however, so the investigators used a metabolomics analysis on serum samples from prospectively observed SFTS patients. “[W]e determined arginine metabolism to be a key pathway that was involved in the interaction between SFTS [virus] and host response,” they wrote.
In a prospective cohort study that used liquid chromatography–tandem mass spectrometry, Dr. Li of the Beijing Institute of Microbiology and Epidemiology and colleagues examined 166 metabolites from 242 clinical samples to perform the metabolomics analysis. Of the SFTS patients in the study, 46 had both acute and convalescent samples that were matched with 46 healthy controls and 46 patients with fever not caused by SFTS. In a separate analysis, a series of samples were drawn from 10 patients who died of SFTS and matched to 10 who survived the infection and 10 healthy controls.
Statistical analyses allowed the investigators to identify metabolomics signatures that were unique for each sample group. Alteration of the arginine metabolism pathway stood out as the most pronounced differentiator in acute SFTS infection and fatality, wrote Dr. Li and coauthors. “By extracting the relative concentrations of arginine-related metabolites along the pathway, we found that arginine RC was significantly reduced in the acute phase of SFTS compared to healthy controls,” they wrote (P less than .001).
Patients who succumbed to SFTS had even lower arginine concentrations than did those who survived; arginine levels climbed during recovery for survivors, but stayed low in serum samples from SFTS fatalities.
There’s a logical mechanism by which arginine could contribute to platelet dysfunction and thrombocytopenia, noted Dr. Li and collaborators: Arginine is a nitric oxide precursor, and this pathway is known to be a potent inhibitor of platelet activation.
Low arginine levels would have the effect of taking the brakes off platelet activation, and the investigators did find increases in platelet-monocyte complexes and platelet apoptosis in SFTS virus infection (P = .007 and P less than .001, respectively), which further suggests “that platelet hyperactivation might contribute to reduced platelet counts in circulation,” they wrote.
Low arginine levels also have the effect of suppressing T-cell activity, and mediators along this pathway were also altered in patients with SFTS, and even more profoundly altered in patients who died of SFTS.
Dr. Li and colleagues probed the metabolomics data to see whether a global arginine bioavailability ratio (GABR), expressed as arginine/(ornithine + citrulline), could be used to prognosticate clinical outcome in SFTS virus infection. After multivariable analysis, they found that decreased GABR was associated with fatality (P = .039). Further, a low GABR early in infection was prognostic of later fatality, with an area under the receiver operating curve (ROC) of 0.713.
In the double-blind, randomized, placebo-controlled trial of arginine supplementation during SFTS, Dr. Li and coinvestigators found that arginine supplementation did not significantly alter most other laboratory values besides liver transaminases. However, blood urea nitrogen concentration was elevated in those who received arginine, and arginine supplementation was also associated with slightly more vomiting. Serum sampling also revealed that platelet activation and T-cell activity were both corrected in patients given arginine, which gives clues to the means by which arginine supplementation might boost host immune response and promote viral clearing and return to homeostasis of clotting pathways.
Limitations of the clinical trial included relatively small sample sizes and the fact that individuals with severe bleeding were excluded from participation in the trial. Also, the study didn’t account for dietary arginine intake, acknowledged Dr. Li and coauthors.
However, the metabolomics and clinical work taken together used state-of-the-art analytic methods and rigorous experimental design to show “the causal relationship between arginine deficiency and platelet deprivation or immunosuppression by SFTSV infection,” wrote Dr. Li and colleagues.
Disturbance in the arginine–nitric oxide pathway is likely “to be a key biochemical pathway that also plays [a] part in other viral hemorrhagic fever,” said the investigators. “The potential of arginine in treating such infectious diseases [with] similar clinical features as SFTS warrants exploration.”
The study was partially funded by a Bayer Investigator Award; Dr. Li and coauthors reported no other conflicts of interest.
SOURCE: Li X-K et al. Sci Transl Med. doi: 10.1126/scitranslmed.aat4162.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: Low arginine bioavailability was associated with increased risk for severe fever with thrombocytopenia syndrome (SFTS) fatality.
Major finding: Arginine bioavailability had an area under the receiver operating curve of 0.713 for predicting fatality.
Study details: A prospective cohort metabolomics study of 242 serum samples from patients with and without SFTS and a randomized, double-blind, placebo-controlled clinical trial of 113 patients given intravenous arginine supplementation or vehicle alone, in conjunction with supportive care.
Disclosures: The study was partially funded by a Bayer Investigator Award; Dr. Li and coauthors reported no other conflicts of interest.
Source: Li X-K et al. Sci Transl Med. doi: 10.1126/scitranslmed.aat4162.
Recommending HPV vaccination: How would you grade yourself?
A few weeks ago, a patient asked whether he could get my opinion on something unrelated to his yellow fever vaccine visit: He asked what I thought about the human papillomavirus (HPV) vaccine. His daughter’s primary care physician (PCP) had recommended it, but he “heard that it wasn’t safe.” We had a brief discussion.
My pediatric training days have long since ended, but I was taught never to miss an opportunity to immunize. In this case, it was to help a parent decide to immunize. This type of encounter is not unusual because, as part of preparing persons for international travel, I review their routine immunizations. When documentation of a vaccine is absent, it is pointed out and often remedied after a brief discussion.
Unfortunately, with HPV, too often parents state “my primary care physician said” it was optional, it was not required, or it was never recommended. Some were told to wait until their child was older, and several have safety concerns as did the parent above. I sometimes hear, “it’s not necessary for my child”; this is usually a clue indicating that the issue is more likely about how HPV is transmitted than what HPV vaccine can prevent. Most have welcomed the opportunity to discuss the vaccine, hear about its benefits, and have their questions answered. All leave with HPV information and are directed to websites that provide accurate information. They are referred to their PCP – hopefully to be immunized.
Three vaccines – meningococcal conjugate vaccine (MCV), Tdap, and HPV vaccine – all are recommended for administration at 11-12 years of age. A booster of MCV is recommended at 16 years. However, let’s focus on HPV. In 2007, HPV administration was recommended by the Advisory Committee on Immunization Practices (ACIP) for girls; by 2011, the recommendation was extended to boys. It was a three-dose schedule expected to be completed by age 13 years. In December 2016, a two-dose schedule administered at least 6 months apart was recommended for teens who initiated immunization at less than 15 years. Three doses were still recommended for those initiating HPV after 15 years. This was the only time the number of doses to complete a vaccine series had been decreased based on postlicensure data. So
Vaccine coverage
The National Immunization Survey–Teen (NIS-Teen) monitors vaccine coverage annually amongst adolescents aged 13-17 years. Data are obtained from individuals from every state, as well as the District of Columbia, the U.S. Virgin Islands, and six major urban areas.
According to the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2018 Aug 24;67[33]:909-17), HPV vaccination continues to lag behind Tdap and MCV in 2018. Among all adolescents, coverage with one or more doses of HPV was 66%, with up-to-date HPV status in 49%. In contrast, 82% received a dose of MCV, and 89% received a dose of Tdap.
Coverage for receiving one or more doses of HPV among females was 69%, and up-to-date HPV status was 53%; among males, coverage with one or more doses was 63%, and up-to-date HPV status was 44%.
Up-to-date HPV coverage status differed geographically, ranging from 29% in Mississippi to 78% in DC. Overall, eight states and the District of Columbia reported increases in up-to-date status (District of Columbia, Louisiana, Massachusetts, Nebraska, North Carolina, South Carolina, Texas, Vermont, and Virginia). Kudos to Virginia for having the largest increase (20 percentage points).
Coverage also differed between urban and rural areas: one or more doses at 70% vs. 59% and up-to-date status at 52% vs. 42%.
HPV coverage differed by poverty level as well. It was higher for persons living below the poverty level, with one or more doses in 73% and up-to-date status in 54%, compared with persons living at or above poverty level at 63% and 47%, respectively.
HPV-related cancers
The most recent CDC data regarding types of HPV-associated cancers during 2011-2015 suggest that HPV types 16 and 18 account for the majority of cervical (78%) and oropharyngeal (86%) cancers.
Currently, there are more cases of oropharyngeal cancer than cervical, and we have no screening tool for the former.
Safety
Safety has been well documented. Since licensure, no serious safety concerns have been identified, contrary to what has been reported on various social and news media outlets. Yet it remains a concern for many parents who have delayed initiation of vaccine. Efficacy also has been documented in the United States and abroad.
Suggestions for improving HPV immunization coverage
Here are eight suggestions to help you recommend the vaccine and convince hesitant parents of its necessity:
1. Focus on your delivery of the HPV immunization recommendation. Clinician recommendation is the No. 1 reason parents vaccinate. The tone you use and how you make the recommendation can affect how the parent perceives the importance of this vaccine. The following are components of a high-quality recommendation (Academic Pediatrics. 2018;18:S23-S27):
- Routinely recommend vaccine at 11-12 years.
- Recommend vaccine for all preteens, not just those you feel are at risk for infection.
- Recommend the vaccine be given the same day it is discussed.
- Use language that expresses the importance of the HPV vaccine.
2. Use the “announcement or presumptive approach.” You expect the parent to agree with your recommendation. You don’t want to convey that it is an option.
3. Remind parents that immunizing on time means only two doses of HPV.
4. Revisit the topic again during another visit if a parent declines. Data suggest secondary acceptance can be as high as 66%.
5. Consider using a motivational interviewing approach for parents who are very hesitant to vaccinate. Most people want to comply with recommended health interventions.
6. Educate your staff about the importance of HPV vaccine and how it prevents cancer.
7. Determine how well your practice immunizes adolescents. This would be a perfect quality improvement project.
8. Explore “Answering Parents’ Questions” and other resources at www.cdc.gov/hpv to find quick answers to HPV vaccine–related questions .
Why is HPV coverage, a vaccine to prevent cancer, still lagging behind Tdap and MCV? I am as puzzled as others. What I do know is this: Our children will mature and one day become sexually active. They can be exposed to and get infected with HPV, and we can’t predict which ones will not clear the virus and end up developing an HPV-related cancer in the future. At the end of the day, HPV vaccination is cancer prevention.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
A few weeks ago, a patient asked whether he could get my opinion on something unrelated to his yellow fever vaccine visit: He asked what I thought about the human papillomavirus (HPV) vaccine. His daughter’s primary care physician (PCP) had recommended it, but he “heard that it wasn’t safe.” We had a brief discussion.
My pediatric training days have long since ended, but I was taught never to miss an opportunity to immunize. In this case, it was to help a parent decide to immunize. This type of encounter is not unusual because, as part of preparing persons for international travel, I review their routine immunizations. When documentation of a vaccine is absent, it is pointed out and often remedied after a brief discussion.
Unfortunately, with HPV, too often parents state “my primary care physician said” it was optional, it was not required, or it was never recommended. Some were told to wait until their child was older, and several have safety concerns as did the parent above. I sometimes hear, “it’s not necessary for my child”; this is usually a clue indicating that the issue is more likely about how HPV is transmitted than what HPV vaccine can prevent. Most have welcomed the opportunity to discuss the vaccine, hear about its benefits, and have their questions answered. All leave with HPV information and are directed to websites that provide accurate information. They are referred to their PCP – hopefully to be immunized.
Three vaccines – meningococcal conjugate vaccine (MCV), Tdap, and HPV vaccine – all are recommended for administration at 11-12 years of age. A booster of MCV is recommended at 16 years. However, let’s focus on HPV. In 2007, HPV administration was recommended by the Advisory Committee on Immunization Practices (ACIP) for girls; by 2011, the recommendation was extended to boys. It was a three-dose schedule expected to be completed by age 13 years. In December 2016, a two-dose schedule administered at least 6 months apart was recommended for teens who initiated immunization at less than 15 years. Three doses were still recommended for those initiating HPV after 15 years. This was the only time the number of doses to complete a vaccine series had been decreased based on postlicensure data. So
Vaccine coverage
The National Immunization Survey–Teen (NIS-Teen) monitors vaccine coverage annually amongst adolescents aged 13-17 years. Data are obtained from individuals from every state, as well as the District of Columbia, the U.S. Virgin Islands, and six major urban areas.
According to the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2018 Aug 24;67[33]:909-17), HPV vaccination continues to lag behind Tdap and MCV in 2018. Among all adolescents, coverage with one or more doses of HPV was 66%, with up-to-date HPV status in 49%. In contrast, 82% received a dose of MCV, and 89% received a dose of Tdap.
Coverage for receiving one or more doses of HPV among females was 69%, and up-to-date HPV status was 53%; among males, coverage with one or more doses was 63%, and up-to-date HPV status was 44%.
Up-to-date HPV coverage status differed geographically, ranging from 29% in Mississippi to 78% in DC. Overall, eight states and the District of Columbia reported increases in up-to-date status (District of Columbia, Louisiana, Massachusetts, Nebraska, North Carolina, South Carolina, Texas, Vermont, and Virginia). Kudos to Virginia for having the largest increase (20 percentage points).
Coverage also differed between urban and rural areas: one or more doses at 70% vs. 59% and up-to-date status at 52% vs. 42%.
HPV coverage differed by poverty level as well. It was higher for persons living below the poverty level, with one or more doses in 73% and up-to-date status in 54%, compared with persons living at or above poverty level at 63% and 47%, respectively.
HPV-related cancers
The most recent CDC data regarding types of HPV-associated cancers during 2011-2015 suggest that HPV types 16 and 18 account for the majority of cervical (78%) and oropharyngeal (86%) cancers.
Currently, there are more cases of oropharyngeal cancer than cervical, and we have no screening tool for the former.
Safety
Safety has been well documented. Since licensure, no serious safety concerns have been identified, contrary to what has been reported on various social and news media outlets. Yet it remains a concern for many parents who have delayed initiation of vaccine. Efficacy also has been documented in the United States and abroad.
Suggestions for improving HPV immunization coverage
Here are eight suggestions to help you recommend the vaccine and convince hesitant parents of its necessity:
1. Focus on your delivery of the HPV immunization recommendation. Clinician recommendation is the No. 1 reason parents vaccinate. The tone you use and how you make the recommendation can affect how the parent perceives the importance of this vaccine. The following are components of a high-quality recommendation (Academic Pediatrics. 2018;18:S23-S27):
- Routinely recommend vaccine at 11-12 years.
- Recommend vaccine for all preteens, not just those you feel are at risk for infection.
- Recommend the vaccine be given the same day it is discussed.
- Use language that expresses the importance of the HPV vaccine.
2. Use the “announcement or presumptive approach.” You expect the parent to agree with your recommendation. You don’t want to convey that it is an option.
3. Remind parents that immunizing on time means only two doses of HPV.
4. Revisit the topic again during another visit if a parent declines. Data suggest secondary acceptance can be as high as 66%.
5. Consider using a motivational interviewing approach for parents who are very hesitant to vaccinate. Most people want to comply with recommended health interventions.
6. Educate your staff about the importance of HPV vaccine and how it prevents cancer.
7. Determine how well your practice immunizes adolescents. This would be a perfect quality improvement project.
8. Explore “Answering Parents’ Questions” and other resources at www.cdc.gov/hpv to find quick answers to HPV vaccine–related questions .
Why is HPV coverage, a vaccine to prevent cancer, still lagging behind Tdap and MCV? I am as puzzled as others. What I do know is this: Our children will mature and one day become sexually active. They can be exposed to and get infected with HPV, and we can’t predict which ones will not clear the virus and end up developing an HPV-related cancer in the future. At the end of the day, HPV vaccination is cancer prevention.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
A few weeks ago, a patient asked whether he could get my opinion on something unrelated to his yellow fever vaccine visit: He asked what I thought about the human papillomavirus (HPV) vaccine. His daughter’s primary care physician (PCP) had recommended it, but he “heard that it wasn’t safe.” We had a brief discussion.
My pediatric training days have long since ended, but I was taught never to miss an opportunity to immunize. In this case, it was to help a parent decide to immunize. This type of encounter is not unusual because, as part of preparing persons for international travel, I review their routine immunizations. When documentation of a vaccine is absent, it is pointed out and often remedied after a brief discussion.
Unfortunately, with HPV, too often parents state “my primary care physician said” it was optional, it was not required, or it was never recommended. Some were told to wait until their child was older, and several have safety concerns as did the parent above. I sometimes hear, “it’s not necessary for my child”; this is usually a clue indicating that the issue is more likely about how HPV is transmitted than what HPV vaccine can prevent. Most have welcomed the opportunity to discuss the vaccine, hear about its benefits, and have their questions answered. All leave with HPV information and are directed to websites that provide accurate information. They are referred to their PCP – hopefully to be immunized.
Three vaccines – meningococcal conjugate vaccine (MCV), Tdap, and HPV vaccine – all are recommended for administration at 11-12 years of age. A booster of MCV is recommended at 16 years. However, let’s focus on HPV. In 2007, HPV administration was recommended by the Advisory Committee on Immunization Practices (ACIP) for girls; by 2011, the recommendation was extended to boys. It was a three-dose schedule expected to be completed by age 13 years. In December 2016, a two-dose schedule administered at least 6 months apart was recommended for teens who initiated immunization at less than 15 years. Three doses were still recommended for those initiating HPV after 15 years. This was the only time the number of doses to complete a vaccine series had been decreased based on postlicensure data. So
Vaccine coverage
The National Immunization Survey–Teen (NIS-Teen) monitors vaccine coverage annually amongst adolescents aged 13-17 years. Data are obtained from individuals from every state, as well as the District of Columbia, the U.S. Virgin Islands, and six major urban areas.
According to the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2018 Aug 24;67[33]:909-17), HPV vaccination continues to lag behind Tdap and MCV in 2018. Among all adolescents, coverage with one or more doses of HPV was 66%, with up-to-date HPV status in 49%. In contrast, 82% received a dose of MCV, and 89% received a dose of Tdap.
Coverage for receiving one or more doses of HPV among females was 69%, and up-to-date HPV status was 53%; among males, coverage with one or more doses was 63%, and up-to-date HPV status was 44%.
Up-to-date HPV coverage status differed geographically, ranging from 29% in Mississippi to 78% in DC. Overall, eight states and the District of Columbia reported increases in up-to-date status (District of Columbia, Louisiana, Massachusetts, Nebraska, North Carolina, South Carolina, Texas, Vermont, and Virginia). Kudos to Virginia for having the largest increase (20 percentage points).
Coverage also differed between urban and rural areas: one or more doses at 70% vs. 59% and up-to-date status at 52% vs. 42%.
HPV coverage differed by poverty level as well. It was higher for persons living below the poverty level, with one or more doses in 73% and up-to-date status in 54%, compared with persons living at or above poverty level at 63% and 47%, respectively.
HPV-related cancers
The most recent CDC data regarding types of HPV-associated cancers during 2011-2015 suggest that HPV types 16 and 18 account for the majority of cervical (78%) and oropharyngeal (86%) cancers.
Currently, there are more cases of oropharyngeal cancer than cervical, and we have no screening tool for the former.
Safety
Safety has been well documented. Since licensure, no serious safety concerns have been identified, contrary to what has been reported on various social and news media outlets. Yet it remains a concern for many parents who have delayed initiation of vaccine. Efficacy also has been documented in the United States and abroad.
Suggestions for improving HPV immunization coverage
Here are eight suggestions to help you recommend the vaccine and convince hesitant parents of its necessity:
1. Focus on your delivery of the HPV immunization recommendation. Clinician recommendation is the No. 1 reason parents vaccinate. The tone you use and how you make the recommendation can affect how the parent perceives the importance of this vaccine. The following are components of a high-quality recommendation (Academic Pediatrics. 2018;18:S23-S27):
- Routinely recommend vaccine at 11-12 years.
- Recommend vaccine for all preteens, not just those you feel are at risk for infection.
- Recommend the vaccine be given the same day it is discussed.
- Use language that expresses the importance of the HPV vaccine.
2. Use the “announcement or presumptive approach.” You expect the parent to agree with your recommendation. You don’t want to convey that it is an option.
3. Remind parents that immunizing on time means only two doses of HPV.
4. Revisit the topic again during another visit if a parent declines. Data suggest secondary acceptance can be as high as 66%.
5. Consider using a motivational interviewing approach for parents who are very hesitant to vaccinate. Most people want to comply with recommended health interventions.
6. Educate your staff about the importance of HPV vaccine and how it prevents cancer.
7. Determine how well your practice immunizes adolescents. This would be a perfect quality improvement project.
8. Explore “Answering Parents’ Questions” and other resources at www.cdc.gov/hpv to find quick answers to HPV vaccine–related questions .
Why is HPV coverage, a vaccine to prevent cancer, still lagging behind Tdap and MCV? I am as puzzled as others. What I do know is this: Our children will mature and one day become sexually active. They can be exposed to and get infected with HPV, and we can’t predict which ones will not clear the virus and end up developing an HPV-related cancer in the future. At the end of the day, HPV vaccination is cancer prevention.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
Educate your adolescent patients about herpes
We are all familiar with the line, “Herpes lasts forever.” There is no cure for infection with a herpes virus, whether it is herpes simplex 1 (HSV-1) or herpes simplex 2 (HSV-2).
There are antivirals to reduce the length and severity of flare-ups, and continued therapy can suppress the virus, which reduces shedding. Both HSV-1 and HSV-2 can cause genital herpes and oral herpes, i.e. cold sores. HSV-1 has a milder initial episode and fewer flareups, whereas HSV-2 can have a more severe initial episode and frequent flareups.1
According to data from the National Health and Nutrition Examination Survey (NHANES) for 2015-2016, HSV-1 prevalence was 48% among 14- to 19-year-olds and HSV-2 prevalence was 12% in the same age group. Overall, age-adjusted HSV-1 prevalence was higher in females (51%) than in males (45%) in persons aged 14-49 years.2
The reality is that most people with HSV-1 or HSV-2 don’t even know they have it, as both tend to be asymptomatic. Therefore, all reported statistics are grossly underrepresenting the prevalence of the disease.
HSV is a common disease. Regardless of symptoms, shedding occurs. Although condoms reduce the risk of spread, using one doesn’t eliminate it because of the possibility of contact beyond the area covered by the condom and the ability of HSV to be passed through oral sex. The only true prevention is abstinence.
Herpes simplex virus is a sexually transmitted infection that is lifelong. Its presence can increase the risk of contracting HIV. If it is contracted in the third trimester of pregnancy or if a breakout occurs during the third trimester, risk of transmitting to the infant can occur, with devastating neurological impact. Despite the seriousness and longevity of the virus, the vast majority of people with the virus have it unknowingly, and live normal healthy lives.
It is just as important that we educate them that, if they contract herpes, it is not end of their ability to have intimate relationships. Debunking the myth that HSV-2 is a worse disease to have than HSV-1 can significantly reduce the psychological burden caused by this disease, and encourage patients to be more honest about their diagnosis. This not only will assist people in seeking medical advice if they have concerns, but it will encourage conversations about HSV, which hopefully will reduce spread of the virus.
Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. J Infect Dis. 2014 Feb. doi: 10.1093/infdis/jit458.
2. NCHS Data Brief, no 304. 2018 Feb.
We are all familiar with the line, “Herpes lasts forever.” There is no cure for infection with a herpes virus, whether it is herpes simplex 1 (HSV-1) or herpes simplex 2 (HSV-2).
There are antivirals to reduce the length and severity of flare-ups, and continued therapy can suppress the virus, which reduces shedding. Both HSV-1 and HSV-2 can cause genital herpes and oral herpes, i.e. cold sores. HSV-1 has a milder initial episode and fewer flareups, whereas HSV-2 can have a more severe initial episode and frequent flareups.1
According to data from the National Health and Nutrition Examination Survey (NHANES) for 2015-2016, HSV-1 prevalence was 48% among 14- to 19-year-olds and HSV-2 prevalence was 12% in the same age group. Overall, age-adjusted HSV-1 prevalence was higher in females (51%) than in males (45%) in persons aged 14-49 years.2
The reality is that most people with HSV-1 or HSV-2 don’t even know they have it, as both tend to be asymptomatic. Therefore, all reported statistics are grossly underrepresenting the prevalence of the disease.
HSV is a common disease. Regardless of symptoms, shedding occurs. Although condoms reduce the risk of spread, using one doesn’t eliminate it because of the possibility of contact beyond the area covered by the condom and the ability of HSV to be passed through oral sex. The only true prevention is abstinence.
Herpes simplex virus is a sexually transmitted infection that is lifelong. Its presence can increase the risk of contracting HIV. If it is contracted in the third trimester of pregnancy or if a breakout occurs during the third trimester, risk of transmitting to the infant can occur, with devastating neurological impact. Despite the seriousness and longevity of the virus, the vast majority of people with the virus have it unknowingly, and live normal healthy lives.
It is just as important that we educate them that, if they contract herpes, it is not end of their ability to have intimate relationships. Debunking the myth that HSV-2 is a worse disease to have than HSV-1 can significantly reduce the psychological burden caused by this disease, and encourage patients to be more honest about their diagnosis. This not only will assist people in seeking medical advice if they have concerns, but it will encourage conversations about HSV, which hopefully will reduce spread of the virus.
Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. J Infect Dis. 2014 Feb. doi: 10.1093/infdis/jit458.
2. NCHS Data Brief, no 304. 2018 Feb.
We are all familiar with the line, “Herpes lasts forever.” There is no cure for infection with a herpes virus, whether it is herpes simplex 1 (HSV-1) or herpes simplex 2 (HSV-2).
There are antivirals to reduce the length and severity of flare-ups, and continued therapy can suppress the virus, which reduces shedding. Both HSV-1 and HSV-2 can cause genital herpes and oral herpes, i.e. cold sores. HSV-1 has a milder initial episode and fewer flareups, whereas HSV-2 can have a more severe initial episode and frequent flareups.1
According to data from the National Health and Nutrition Examination Survey (NHANES) for 2015-2016, HSV-1 prevalence was 48% among 14- to 19-year-olds and HSV-2 prevalence was 12% in the same age group. Overall, age-adjusted HSV-1 prevalence was higher in females (51%) than in males (45%) in persons aged 14-49 years.2
The reality is that most people with HSV-1 or HSV-2 don’t even know they have it, as both tend to be asymptomatic. Therefore, all reported statistics are grossly underrepresenting the prevalence of the disease.
HSV is a common disease. Regardless of symptoms, shedding occurs. Although condoms reduce the risk of spread, using one doesn’t eliminate it because of the possibility of contact beyond the area covered by the condom and the ability of HSV to be passed through oral sex. The only true prevention is abstinence.
Herpes simplex virus is a sexually transmitted infection that is lifelong. Its presence can increase the risk of contracting HIV. If it is contracted in the third trimester of pregnancy or if a breakout occurs during the third trimester, risk of transmitting to the infant can occur, with devastating neurological impact. Despite the seriousness and longevity of the virus, the vast majority of people with the virus have it unknowingly, and live normal healthy lives.
It is just as important that we educate them that, if they contract herpes, it is not end of their ability to have intimate relationships. Debunking the myth that HSV-2 is a worse disease to have than HSV-1 can significantly reduce the psychological burden caused by this disease, and encourage patients to be more honest about their diagnosis. This not only will assist people in seeking medical advice if they have concerns, but it will encourage conversations about HSV, which hopefully will reduce spread of the virus.
Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. J Infect Dis. 2014 Feb. doi: 10.1093/infdis/jit458.
2. NCHS Data Brief, no 304. 2018 Feb.
Congenital syphilis rates continue skyrocketing alongside other STDs
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Rapidly increasing cases of newborn syphilis have reached their highest prevalence in 2 decades, according to a new report by the Centers for Disease Control and Prevention on sexually transmitted disease surveillance in 2017.
Newborn syphilis incidence has more than doubled, from 362 cases in 2013 to 918 cases in 2017, resulting in 64 syphilitic stillbirths and 13 infant deaths that year, according to data published in Sexually Transmitted Disease Surveillance 2017.
At least one case was reported in 37 states last year, and the greatest burden of cases occurred in California, Arizona, Texas, Louisiana, and Florida, together accounting for 70% of all 2017 cases.
“The resurgence of syphilis, and particularly congenital syphilis, is not an arbitrary event, but rather a symptom of a deteriorating public health infrastructure and lack of access to health care,” wrote Gail Bolan, MD, director of the Division of STD Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “It is exposing hidden, fragile populations in need that are not getting the health care and preventive services they deserve.”
Dr. Bolan recommends modernizing surveillance to capture more of the cases in populations without ready access to diagnosis and treatment and in those choosing not to access care.
“It is imperative that federal, state, and local programs employ strategies that maximize long-term population impact by reducing STD incidence and promoting sexual, reproductive, maternal, and infant health,” she wrote. “Further, it will be important for us to measure and monitor the adverse health consequences of STDs, such as ocular and neurosyphilis, pelvic inflammatory disease, ectopic pregnancy, infertility, HIV, congenital syphilis, and neonatal herpes.”
Multiple sources contributed data to the report: state and local STD programs’ notifiable disease reporting, private and federal national surveys, and specific projects that collect STD prevalence data, including the National Job Training Program, the STD Surveillance Network and the Gonococcal Isolate Surveillance Project.
The four nationally notifiable STDs are chlamydia, gonorrhea, syphilis, and chancroid.
The rise in newborn syphilis cases, currently at 23.3 cases per 100,000 live births, mirrors the increased U.S. prevalence of both primary and secondary syphilis in 2017, with 9.5 cases per 100,000 people. Syphilis has increased every year since 2000-2001, when prevalence was at a record low.
Chlamydia and gonorrhea rates climb too
The report also noted increases in the prevalence of other STDs. Chlamydia, the most common STD, increased 6.9% as compared to 2016, with 528.8 cases per 100,000 people. This increase occurred in all U.S. regions and independently of sex, race, or ethnicity, though rates were highest in teens and young adults. Nearly two-thirds of chlamydia cases in 2017 occurred in people ages 15-24 years old.
Reported rates were higher in women than in men, likely due to women’s increased likelihood of undergoing screening, the report suggested. Better surveillance may also partly explain the climb in men’s cases.
“Increases in rates among men may reflect an increased number of men, including gay, bisexual and other men who have sex with men (collectively referred to as MSM) being tested and diagnosed with a chlamydial infection due to increased availability of urine testing and extragenital screening,” according to the report.
The CDC received reports of more than a half million gonorrhea infections in 2017 (555,608 cases), an increase of 18.6% since the previous year, including a 19.3% increase among men and a 17.8% increase among women.
“The magnitude of the increase among men suggests either increased transmission, increased case ascertainment (e.g., through increased extra-genital screening among MSM), or both,” the authors wrote. “The concurrent increase in cases reported among women suggests parallel increases in heterosexual transmission, increased screening among women, or both.”
Overall, gonorrhea cases have skyrocketed 75.2% since their historic low in 2009, compounding the problem of antibiotic resistance that has limited CDC-recommended treatment to just ceftriaxone and azithromycin.
The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
SOURCE: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017; https://www.cdc.gov/std/stats
Key clinical point: Newborn syphilis cases have more than doubled in 5 years along with substantial increases in chlamydia, gonorrhea, and syphilis.
Major finding: 918 cases of newborn syphilis were reported in 37 states in 2017.
Study details: The findings are based on data from public health notifiable disease reports and multiple federal and private surveillance projects.
Disclosures: The report was supported by the Centers for Disease Control and Prevention. The authors did not report having any disclosures.
Source: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017.
Perianal Ulceration and Verrucous Papules
The Diagnosis: Herpes Simplex Virus Infection
Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.
Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.1 Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.2 This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.6 Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.7-10
Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.
Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.3,5,6,11
- Ranu H, Lee J, Chio M, et al. Tumour-like presentations of anogenital herpes simplex in HIV-positive patients. Int J STD AIDS. 2011;22:181-186.
- Tong P, Mutasim DF. Herpes simplex virus infection masquerading as condylomata accuminata in a patient with HIV disease. Br J Dermatol. 1996;134:797-800.
- Mosunjac M, Park J, Wang W, et al. Genital and perianal herpes simplex simulating neoplasia in patients with AIDS. AIDS Patient Care STDS. 2009;23:153-158.
- Gubinelli E, Cocuroccia B, Lazzarotto T, et al. Nodular perianal herpes simplex with prominent plasma cell infiltration. Sexually Transm Dis. 2003;30:157-159.
- Nadal SR, Calore EE, Manzione CR, et al. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases. Dis Colon Rectum. 2005;48:2289-2293.
- Beasley KL, Cooley GE, Kao GF, et al. Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol. 1997;37(5, pt 2):860-863.
- Burke EM, Karp DL, Wu TC, et al. Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation. Eur Arch Otorhinolaryngol. 1994;251:301-303.
- Tabaee A, Saltman B, Shutter J, et al. Recurrent oral herpes simplex virus infection presenting as a tongue mass. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:376-380.
- Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer. 1984;54:3043-3047.
- Burgoyne M, Burke W. Atypical herpes simplex infection in patients with acute myelogenous leukemia recovering from chemotherapy. J Am Acad Dermatol. 1989;20:1125-1126.
- Deza G, Martin-Ezquerra G, Curto-Barredo L, et al. Successful treatment of hypertrophic herpes simplex genitalis in HIV-infected patient with topical imiquimod. J Dermatol. 2015;42:1176-1178.
The Diagnosis: Herpes Simplex Virus Infection
Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.
Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.1 Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.2 This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.6 Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.7-10
Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.
Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.3,5,6,11
The Diagnosis: Herpes Simplex Virus Infection
Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.
Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.1 Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.2 This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.6 Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.7-10
Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.
Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.3,5,6,11
- Ranu H, Lee J, Chio M, et al. Tumour-like presentations of anogenital herpes simplex in HIV-positive patients. Int J STD AIDS. 2011;22:181-186.
- Tong P, Mutasim DF. Herpes simplex virus infection masquerading as condylomata accuminata in a patient with HIV disease. Br J Dermatol. 1996;134:797-800.
- Mosunjac M, Park J, Wang W, et al. Genital and perianal herpes simplex simulating neoplasia in patients with AIDS. AIDS Patient Care STDS. 2009;23:153-158.
- Gubinelli E, Cocuroccia B, Lazzarotto T, et al. Nodular perianal herpes simplex with prominent plasma cell infiltration. Sexually Transm Dis. 2003;30:157-159.
- Nadal SR, Calore EE, Manzione CR, et al. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases. Dis Colon Rectum. 2005;48:2289-2293.
- Beasley KL, Cooley GE, Kao GF, et al. Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol. 1997;37(5, pt 2):860-863.
- Burke EM, Karp DL, Wu TC, et al. Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation. Eur Arch Otorhinolaryngol. 1994;251:301-303.
- Tabaee A, Saltman B, Shutter J, et al. Recurrent oral herpes simplex virus infection presenting as a tongue mass. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:376-380.
- Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer. 1984;54:3043-3047.
- Burgoyne M, Burke W. Atypical herpes simplex infection in patients with acute myelogenous leukemia recovering from chemotherapy. J Am Acad Dermatol. 1989;20:1125-1126.
- Deza G, Martin-Ezquerra G, Curto-Barredo L, et al. Successful treatment of hypertrophic herpes simplex genitalis in HIV-infected patient with topical imiquimod. J Dermatol. 2015;42:1176-1178.
- Ranu H, Lee J, Chio M, et al. Tumour-like presentations of anogenital herpes simplex in HIV-positive patients. Int J STD AIDS. 2011;22:181-186.
- Tong P, Mutasim DF. Herpes simplex virus infection masquerading as condylomata accuminata in a patient with HIV disease. Br J Dermatol. 1996;134:797-800.
- Mosunjac M, Park J, Wang W, et al. Genital and perianal herpes simplex simulating neoplasia in patients with AIDS. AIDS Patient Care STDS. 2009;23:153-158.
- Gubinelli E, Cocuroccia B, Lazzarotto T, et al. Nodular perianal herpes simplex with prominent plasma cell infiltration. Sexually Transm Dis. 2003;30:157-159.
- Nadal SR, Calore EE, Manzione CR, et al. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases. Dis Colon Rectum. 2005;48:2289-2293.
- Beasley KL, Cooley GE, Kao GF, et al. Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol. 1997;37(5, pt 2):860-863.
- Burke EM, Karp DL, Wu TC, et al. Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation. Eur Arch Otorhinolaryngol. 1994;251:301-303.
- Tabaee A, Saltman B, Shutter J, et al. Recurrent oral herpes simplex virus infection presenting as a tongue mass. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:376-380.
- Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer. 1984;54:3043-3047.
- Burgoyne M, Burke W. Atypical herpes simplex infection in patients with acute myelogenous leukemia recovering from chemotherapy. J Am Acad Dermatol. 1989;20:1125-1126.
- Deza G, Martin-Ezquerra G, Curto-Barredo L, et al. Successful treatment of hypertrophic herpes simplex genitalis in HIV-infected patient with topical imiquimod. J Dermatol. 2015;42:1176-1178.
A 75-year-old woman with chronic lymphocytic leukemia undergoing ibrutinib targeted therapy presented to the emergency department with fever and perianal pain of 4 months' duration. The patient denied history of genital or perianal ulcers, warts, masses, bedsores, prolonged immobilization, anal surgeries, or recent travel. She had not been previously treated for the perianal pain. On physical examination there was an 18×15-cm shallow ulceration with rolled borders involving the intergluteal cleft and perianal area. There were numerous hyperpigmented verrucous papules clustered in the center of the ulceration. No vesicles or bullae were present. Laboratory results were pertinent for a white blood cell count of 3600/µL (reference range, 4500-11,000/µL) and absolute neutrophil count of 1300/µL (reference range, 1900-8000/µL). Human immunodeficiency virus testing was negative.
Residents curb IV antibiotic overuse in children
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
REPORTING FROM PHM 2018
Key clinical point:
Major finding: The percentage of antibiotics given orally to children who were taking other enteral medications rose from 44% to 80% over 8 months, saving an estimated $30,000 annually.
Study details: Quality improvement project
Disclosures: There was no external funding, and the investigators didn’t have any disclosures.