Infectious Diseases

So why are we, the trustworthy, having such a tough time convincing people to get routine vaccines for themselves and for their kids? In a sea of truthopenia, we need to do more.

Not everyone refuses vaccines. It is the rare patient in my examination room who, after a discussion, still steadfastly refuses to get a flu shot or pneumonia vaccine. But our dialogue has changed somewhat. Patients still tell me that they or someone they know got the flu from the flu shot or got sick from the pneumonia vaccine (explainable by discussing the immune system’s systemic anamnestic response to a vaccine in the setting of partial immunity—“It’s a good thing”). But more often, I’m hearing detailed stories from the Internet or social media. We heard a less-than-endorsing reflection on the value of vaccines from 2 potential presidential candidates, 1 being a physician, during a televised presidential primary debate. Then there are the tabloid stories, and, of course, there are the celebrity authors and TV talk show doctors touting the unsubstantiated or incompletely substantiated virtues of “anti-inflammatory” and “immune-boosting” diets and supplements as obvious and total truth, while I’m  recommending vaccinations and traditional drug therapies. Who can the patient believe? In our limited office-visit time, we must somehow put this external noise into perspective and individualize our suggestions for the patient in front of us.

Certainly the major news media research teams and the on-screen physician consultants to the major news networks have offered up evidence-based discussions on vaccination, the impact of preventable infections on the unvaccinated, and the limitations and reasonable potential benefits of specific dietary interventions and supplements. Unfortunately, their message is being contaminated by the untrusting aura that surrounds mainstream written and TV media.

Despite physicians’ continued high professional rating in the 2018 Gallup poll, some patients, families, and communities are swayed by arguments offered outside of our offices. And when it comes to our summarizing large studies published in major medical journals, the rolling echo of possible fake news and alternative facts comes to the fore. Can they really trust the establishment? There remains doubt in some patients’ minds.

The problem with measles, as Porter and Goldfarb discuss in this issue of the Journal, is that it is extremely contagious. For “herd immunity” to provide protection and prevent outbreaks, nearly everyone must be vaccinated or have natural immunity from childhood infection. Those who are at special risk from infection include the very young, who have an underdeveloped immune system, and adults who were not appropriately vaccinated (eg, those who may only have gotten a single measles vaccination as a child or whose immune system is weakened by disease or immunosuppressive drugs).

What can we do? We need, as a united front, to know the evidence that supports the relative value of vaccination of our child and adult patients and pass it on. We need to confront, accept, and explain to patients that all vaccines are not 100% successful (measles seems to be pretty close, based on the near-eradication of the disease in vaccinated communities up until now), but that even partial immunity is probably beneficial with all vaccines. We need to have a united front when discussing the bulk of evidence that debunks the vaccination-autism connection. We need to support federal and state funding so that all children can get their routine medical exams and vaccinations. We need to support sufficient financial protection for those companies who in good faith continue to develop and test new and improved vaccines for use in this country and around the world; infections can be introduced by travelers who have passed through areas endemic for infections rarely seen in the United States and who may not be aware of their own infection.

We need to live up to our Gallup poll ranking as highly trusted professionals. And we need to partner with our even more highly trusted nursing colleagues to take every opportunity to inform our patients and fight the spread of disinformation.

The morbilliform rash attributed to measles—and not to a sulfa allergy—should have been a phenomenon of the past. We didn’t need to see it again.

So why are we, the trustworthy, having such a tough time convincing people to get routine vaccines for themselves and for their kids? In a sea of truthopenia, we need to do more.

Not everyone refuses vaccines. It is the rare patient in my examination room who, after a discussion, still steadfastly refuses to get a flu shot or pneumonia vaccine. But our dialogue has changed somewhat. Patients still tell me that they or someone they know got the flu from the flu shot or got sick from the pneumonia vaccine (explainable by discussing the immune system’s systemic anamnestic response to a vaccine in the setting of partial immunity—“It’s a good thing”). But more often, I’m hearing detailed stories from the Internet or social media. We heard a less-than-endorsing reflection on the value of vaccines from 2 potential presidential candidates, 1 being a physician, during a televised presidential primary debate. Then there are the tabloid stories, and, of course, there are the celebrity authors and TV talk show doctors touting the unsubstantiated or incompletely substantiated virtues of “anti-inflammatory” and “immune-boosting” diets and supplements as obvious and total truth, while I’m  recommending vaccinations and traditional drug therapies. Who can the patient believe? In our limited office-visit time, we must somehow put this external noise into perspective and individualize our suggestions for the patient in front of us.

Certainly the major news media research teams and the on-screen physician consultants to the major news networks have offered up evidence-based discussions on vaccination, the impact of preventable infections on the unvaccinated, and the limitations and reasonable potential benefits of specific dietary interventions and supplements. Unfortunately, their message is being contaminated by the untrusting aura that surrounds mainstream written and TV media.

Despite physicians’ continued high professional rating in the 2018 Gallup poll, some patients, families, and communities are swayed by arguments offered outside of our offices. And when it comes to our summarizing large studies published in major medical journals, the rolling echo of possible fake news and alternative facts comes to the fore. Can they really trust the establishment? There remains doubt in some patients’ minds.

The problem with measles, as Porter and Goldfarb discuss in this issue of the Journal, is that it is extremely contagious. For “herd immunity” to provide protection and prevent outbreaks, nearly everyone must be vaccinated or have natural immunity from childhood infection. Those who are at special risk from infection include the very young, who have an underdeveloped immune system, and adults who were not appropriately vaccinated (eg, those who may only have gotten a single measles vaccination as a child or whose immune system is weakened by disease or immunosuppressive drugs).

What can we do? We need, as a united front, to know the evidence that supports the relative value of vaccination of our child and adult patients and pass it on. We need to confront, accept, and explain to patients that all vaccines are not 100% successful (measles seems to be pretty close, based on the near-eradication of the disease in vaccinated communities up until now), but that even partial immunity is probably beneficial with all vaccines. We need to have a united front when discussing the bulk of evidence that debunks the vaccination-autism connection. We need to support federal and state funding so that all children can get their routine medical exams and vaccinations. We need to support sufficient financial protection for those companies who in good faith continue to develop and test new and improved vaccines for use in this country and around the world; infections can be introduced by travelers who have passed through areas endemic for infections rarely seen in the United States and who may not be aware of their own infection.

We need to live up to our Gallup poll ranking as highly trusted professionals. And we need to partner with our even more highly trusted nursing colleagues to take every opportunity to inform our patients and fight the spread of disinformation.

The morbilliform rash attributed to measles—and not to a sulfa allergy—should have been a phenomenon of the past. We didn’t need to see it again.

So why are we, the trustworthy, having such a tough time convincing people to get routine vaccines for themselves and for their kids? In a sea of truthopenia, we need to do more.

Not everyone refuses vaccines. It is the rare patient in my examination room who, after a discussion, still steadfastly refuses to get a flu shot or pneumonia vaccine. But our dialogue has changed somewhat. Patients still tell me that they or someone they know got the flu from the flu shot or got sick from the pneumonia vaccine (explainable by discussing the immune system’s systemic anamnestic response to a vaccine in the setting of partial immunity—“It’s a good thing”). But more often, I’m hearing detailed stories from the Internet or social media. We heard a less-than-endorsing reflection on the value of vaccines from 2 potential presidential candidates, 1 being a physician, during a televised presidential primary debate. Then there are the tabloid stories, and, of course, there are the celebrity authors and TV talk show doctors touting the unsubstantiated or incompletely substantiated virtues of “anti-inflammatory” and “immune-boosting” diets and supplements as obvious and total truth, while I’m  recommending vaccinations and traditional drug therapies. Who can the patient believe? In our limited office-visit time, we must somehow put this external noise into perspective and individualize our suggestions for the patient in front of us.

Certainly the major news media research teams and the on-screen physician consultants to the major news networks have offered up evidence-based discussions on vaccination, the impact of preventable infections on the unvaccinated, and the limitations and reasonable potential benefits of specific dietary interventions and supplements. Unfortunately, their message is being contaminated by the untrusting aura that surrounds mainstream written and TV media.

Despite physicians’ continued high professional rating in the 2018 Gallup poll, some patients, families, and communities are swayed by arguments offered outside of our offices. And when it comes to our summarizing large studies published in major medical journals, the rolling echo of possible fake news and alternative facts comes to the fore. Can they really trust the establishment? There remains doubt in some patients’ minds.

The problem with measles, as Porter and Goldfarb discuss in this issue of the Journal, is that it is extremely contagious. For “herd immunity” to provide protection and prevent outbreaks, nearly everyone must be vaccinated or have natural immunity from childhood infection. Those who are at special risk from infection include the very young, who have an underdeveloped immune system, and adults who were not appropriately vaccinated (eg, those who may only have gotten a single measles vaccination as a child or whose immune system is weakened by disease or immunosuppressive drugs).

What can we do? We need, as a united front, to know the evidence that supports the relative value of vaccination of our child and adult patients and pass it on. We need to confront, accept, and explain to patients that all vaccines are not 100% successful (measles seems to be pretty close, based on the near-eradication of the disease in vaccinated communities up until now), but that even partial immunity is probably beneficial with all vaccines. We need to have a united front when discussing the bulk of evidence that debunks the vaccination-autism connection. We need to support federal and state funding so that all children can get their routine medical exams and vaccinations. We need to support sufficient financial protection for those companies who in good faith continue to develop and test new and improved vaccines for use in this country and around the world; infections can be introduced by travelers who have passed through areas endemic for infections rarely seen in the United States and who may not be aware of their own infection.

We need to live up to our Gallup poll ranking as highly trusted professionals. And we need to partner with our even more highly trusted nursing colleagues to take every opportunity to inform our patients and fight the spread of disinformation.

The morbilliform rash attributed to measles—and not to a sulfa allergy—should have been a phenomenon of the past. We didn’t need to see it again.

A 57-year-old woman was admitted to our hospital for progressive hypoxic respiratory failure that developed after 10 days of empiric treatment at another hospital for an exacerbation of chronic obstructive pulmonary disease (COPD).

Computed tomography (CT) showed a lesion in the upper lobe of the left lung, with new ground-glass opacities with cystic and cavitary changes raising concern for an inflammatory or infectious cause (Figure 1). Respiratory culture of expectorated secretions grew Aspergillus. Assays for beta-d-glucan and serum Aspergillus immunoglobulin G (IgG) antibodies were positive, although given the improvement in her oxygenation requirements and overall clinical status, these were thought to be trivial. Tests for immunoglobulin deficiencies and human immunodeficiency virus were negative, ruling out primary immunodeficiency. However, within the next 48 hours, her respiratory status declined, and voriconazole was started out of concern for invasive pulmonary aspergillosis based on results of serum IgG testing.

Despite 2 days of treatment with voriconazole, the patient developed respiratory failure. Repeat CT showed that the ground-glass opacities were more dense, especially in the lower lobes, and new patchy infiltrates were noted in the left lung. The patient developed a right tension pneumothorax requiring emergency intubation and chest tube insertion.¹ She subsequently developed acute abdominal pain with worsening abdominal distention, diagnosed as pneumoperitoneum. Emergency exploratory laparotomy revealed perforations in the cecum with fecal spillage, requiring ileo­cecectomy and ileostomy.

Pathologic study of bowel specimens confirmed fungal hyphae with “tree-branch” structures consistent with fungal infection in the bowel (Figure 2).

Oral voriconazole was continued. The patient’s respiratory status improved, and she no longer required supplemental oxygen. She was discharged on a regimen of oral voriconazole 200 mg twice daily. However, over the next 12 months, she had additional hospitalizations for severe sepsis from abdominal wound infections, pneumonia, and Clostridium difficile infection. She will require lifelong antifungal treatment.

INVASIVE PULMONARY ASPERGILLOSIS

Invasive pulmonary aspergillosis is the most severe form of aspergillosis and is most often seen in immunocompromised patients. The death rate is as high as 50% in neutropenic patients regardless of the time to diagnosis or effective treatment.² It becomes life-threatening as the infection enters the blood stream, leading to formation of thrombi and precipitating embolism and necrosis in the lungs.³

In immunocompetent patients, COPD, tuberculosis, bronchiectasis, liver disease, severe sepsis, and diabetes mellitus predispose to invasive pulmonary aspergillosis.² Other risk factors include long-term steroid therapy at doses equivalent to prednisone 20 mg/day for at least 13 weeks⁴ and viral infection such as influenza.⁵ Chronic use of inhaled corticosteroids has been hypothesized to increase risk.⁴

Histopathologic confirmation of fungal elements is the gold standard for diagnosis.³ New biomarkers such as beta-d-glucan have shown promise in enabling earlier diagnosis to allow effective treatment of disseminated aspergillosis, as in our patient.⁶

TAKE-HOME MESSAGE

Although not common, invasive aspergillosis can occur in immunocompetent and near-immunocompetent patients, particularly those with COPD or other underlying lung disease.

Acknowledgment: The authors thank Kimberley Woodward, MD, Inova Fairfax Hospital, Falls Church, VA, for her study of the bowel specimen and for providing the histology slide.

A 57-year-old woman was admitted to our hospital for progressive hypoxic respiratory failure that developed after 10 days of empiric treatment at another hospital for an exacerbation of chronic obstructive pulmonary disease (COPD).

Computed tomography (CT) showed a lesion in the upper lobe of the left lung, with new ground-glass opacities with cystic and cavitary changes raising concern for an inflammatory or infectious cause (Figure 1). Respiratory culture of expectorated secretions grew Aspergillus. Assays for beta-d-glucan and serum Aspergillus immunoglobulin G (IgG) antibodies were positive, although given the improvement in her oxygenation requirements and overall clinical status, these were thought to be trivial. Tests for immunoglobulin deficiencies and human immunodeficiency virus were negative, ruling out primary immunodeficiency. However, within the next 48 hours, her respiratory status declined, and voriconazole was started out of concern for invasive pulmonary aspergillosis based on results of serum IgG testing.

Despite 2 days of treatment with voriconazole, the patient developed respiratory failure. Repeat CT showed that the ground-glass opacities were more dense, especially in the lower lobes, and new patchy infiltrates were noted in the left lung. The patient developed a right tension pneumothorax requiring emergency intubation and chest tube insertion.¹ She subsequently developed acute abdominal pain with worsening abdominal distention, diagnosed as pneumoperitoneum. Emergency exploratory laparotomy revealed perforations in the cecum with fecal spillage, requiring ileo­cecectomy and ileostomy.

Pathologic study of bowel specimens confirmed fungal hyphae with “tree-branch” structures consistent with fungal infection in the bowel (Figure 2).

Oral voriconazole was continued. The patient’s respiratory status improved, and she no longer required supplemental oxygen. She was discharged on a regimen of oral voriconazole 200 mg twice daily. However, over the next 12 months, she had additional hospitalizations for severe sepsis from abdominal wound infections, pneumonia, and Clostridium difficile infection. She will require lifelong antifungal treatment.

INVASIVE PULMONARY ASPERGILLOSIS

Invasive pulmonary aspergillosis is the most severe form of aspergillosis and is most often seen in immunocompromised patients. The death rate is as high as 50% in neutropenic patients regardless of the time to diagnosis or effective treatment.² It becomes life-threatening as the infection enters the blood stream, leading to formation of thrombi and precipitating embolism and necrosis in the lungs.³

In immunocompetent patients, COPD, tuberculosis, bronchiectasis, liver disease, severe sepsis, and diabetes mellitus predispose to invasive pulmonary aspergillosis.² Other risk factors include long-term steroid therapy at doses equivalent to prednisone 20 mg/day for at least 13 weeks⁴ and viral infection such as influenza.⁵ Chronic use of inhaled corticosteroids has been hypothesized to increase risk.⁴

Histopathologic confirmation of fungal elements is the gold standard for diagnosis.³ New biomarkers such as beta-d-glucan have shown promise in enabling earlier diagnosis to allow effective treatment of disseminated aspergillosis, as in our patient.⁶

TAKE-HOME MESSAGE

Although not common, invasive aspergillosis can occur in immunocompetent and near-immunocompetent patients, particularly those with COPD or other underlying lung disease.

Acknowledgment: The authors thank Kimberley Woodward, MD, Inova Fairfax Hospital, Falls Church, VA, for her study of the bowel specimen and for providing the histology slide.

A 57-year-old woman was admitted to our hospital for progressive hypoxic respiratory failure that developed after 10 days of empiric treatment at another hospital for an exacerbation of chronic obstructive pulmonary disease (COPD).

Computed tomography (CT) showed a lesion in the upper lobe of the left lung, with new ground-glass opacities with cystic and cavitary changes raising concern for an inflammatory or infectious cause (Figure 1). Respiratory culture of expectorated secretions grew Aspergillus. Assays for beta-d-glucan and serum Aspergillus immunoglobulin G (IgG) antibodies were positive, although given the improvement in her oxygenation requirements and overall clinical status, these were thought to be trivial. Tests for immunoglobulin deficiencies and human immunodeficiency virus were negative, ruling out primary immunodeficiency. However, within the next 48 hours, her respiratory status declined, and voriconazole was started out of concern for invasive pulmonary aspergillosis based on results of serum IgG testing.

Despite 2 days of treatment with voriconazole, the patient developed respiratory failure. Repeat CT showed that the ground-glass opacities were more dense, especially in the lower lobes, and new patchy infiltrates were noted in the left lung. The patient developed a right tension pneumothorax requiring emergency intubation and chest tube insertion.¹ She subsequently developed acute abdominal pain with worsening abdominal distention, diagnosed as pneumoperitoneum. Emergency exploratory laparotomy revealed perforations in the cecum with fecal spillage, requiring ileo­cecectomy and ileostomy.

Pathologic study of bowel specimens confirmed fungal hyphae with “tree-branch” structures consistent with fungal infection in the bowel (Figure 2).

Oral voriconazole was continued. The patient’s respiratory status improved, and she no longer required supplemental oxygen. She was discharged on a regimen of oral voriconazole 200 mg twice daily. However, over the next 12 months, she had additional hospitalizations for severe sepsis from abdominal wound infections, pneumonia, and Clostridium difficile infection. She will require lifelong antifungal treatment.

INVASIVE PULMONARY ASPERGILLOSIS

Invasive pulmonary aspergillosis is the most severe form of aspergillosis and is most often seen in immunocompromised patients. The death rate is as high as 50% in neutropenic patients regardless of the time to diagnosis or effective treatment.² It becomes life-threatening as the infection enters the blood stream, leading to formation of thrombi and precipitating embolism and necrosis in the lungs.³

In immunocompetent patients, COPD, tuberculosis, bronchiectasis, liver disease, severe sepsis, and diabetes mellitus predispose to invasive pulmonary aspergillosis.² Other risk factors include long-term steroid therapy at doses equivalent to prednisone 20 mg/day for at least 13 weeks⁴ and viral infection such as influenza.⁵ Chronic use of inhaled corticosteroids has been hypothesized to increase risk.⁴

Histopathologic confirmation of fungal elements is the gold standard for diagnosis.³ New biomarkers such as beta-d-glucan have shown promise in enabling earlier diagnosis to allow effective treatment of disseminated aspergillosis, as in our patient.⁶

TAKE-HOME MESSAGE

Although not common, invasive aspergillosis can occur in immunocompetent and near-immunocompetent patients, particularly those with COPD or other underlying lung disease.

Acknowledgment: The authors thank Kimberley Woodward, MD, Inova Fairfax Hospital, Falls Church, VA, for her study of the bowel specimen and for providing the histology slide.

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

Reference

Johnson Jones ML, Chapin-Bardales J, Bizune D. Extragenital chlamydia and gonorrhea among community venue –  attending men who have sex with men – Five cities, United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:321-325. https://www.cdc.gov/mmwr/volumes/68/wr/mm6814a1.htm?s_cid=mm6814a1_w. Accessed May 23, 2019.

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

[email protected]

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

[email protected]

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

[email protected]

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]
 

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]
 

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]
 

According to the World Health Organization, there were about 219 million cases of malaria and an estimated 660,000 deaths in 2010. Although huge, this was a 26% decrease from the rates in 2000. Six countries in Africa account for 47% of malaria cases: Cote d’Ivoire, Democratic Republic of the Congo, Mozambique, Nigeria, Uganda, and the United Republic of Tanzania. The second-most affected region in the world is Southeast Asia, which includes Myanmar, India, and Indonesia. In comparison, about 1,500 malaria cases and 5 deaths are reported annually in the United States, mostly from returned travelers.

Courtesy NIAID

It is extremely important for any woman that is or might be pregnant or breastfeeding to take an antimalarial drug for protection if they will be traveling in any of the above regions. Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth.

As stated by the Centers for Disease Control and Prevention, no antimalarial agent is 100% protective. Therefore, whatever agent is used must be combined with personal protective measures such as wearing insect repellent, long sleeves, and long pants; sleeping in a mosquito-free setting; or using an insecticide-treated bed net.

There are nine antimalarial drugs available in the United States.

Atovaquone/Proguanil Hcl (Malarone and as generic)

This agent is good for last-minute travelers because the drug is started 1-2 days before traveling to areas where malaria transmission occurs. The combination can be classified as compatible in pregnancy. No reports in breastfeeding with atovaquone or the combination have been found. Proguanil is not available in the United States as a single agent.

Chloroquine (generic)

This is the drug of choice to prevent and treat sensitive malaria species during pregnancy. The drug crosses the placenta producing fetal concentrations that are similar to those in the mother. The drug appears to be low risk for embryo-fetal harm.

It is compatible in breastfeeding.

Dapsone (generic)

This agent does not appear to represent a major risk of harm to the fetus. Although it has been used in combination with pyrimethamine (an antiparasitic) or trimethoprim (an antibiotic) to prevent malaria, the efficacy of the combination has not been confirmed.

In breastfeeding, there is one case of mild hemolytic anemia in the mother and her breastfeeding infant that may have been caused by the drug.

Hydroxychloroquine (generic)

This agent is used for the treatment of malaria, systemic erythematosus, and rheumatoid arthritis. For antimalarial prophylaxis, 400 mg/week appears to be low risk for embryo-fetal harm. Doses used to treat malaria have been 200-400 mg/day.

Because very low concentrations of the drug have been found in breast milk, breastfeeding is probably compatible.

Mefloquine (generic)

This agent is a quinoline-methanol agent that does not appear to cause embryo-fetal harm based on a large number of pregnancy exposures.

There are no reports of its use while breastfeeding.

Primaquine (generic)

This agent is best avoided in pregnancy. There is no human pregnancy data, but it may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Because the fetus is relatively G6PD deficient, it is best avoided in pregnancy regardless of the mother’s status.

There are no reports describing the use of the drug during lactation. Both the mother and baby should be tested for G6PD deficiency before the drug is used during breastfeeding.

Pyrimethamine (generic)

This agent has been used for the treatment or prophylaxis of malaria. Most studies have found this agent to be relatively safe and effective.

It is excreted into breast milk and has been effective in eliminating malaria parasites from breastfeeding infants.

Quinidine (generic)

Reports linking the use of this agent with congenital defects have not been found. Although the drug has data on its use as an antiarrhythmic, its published use to treat malaria is limited.

The drug is excreted into breast milk, but there are no reports of its during breastfeeding.

Quinine (generic)

This agent has a large amount of human pregnancy data (more than 1,000 exposures) that found no increased risk of birth defects. The drug has been replaced by newer agents but still may be used for chloroquine-resistant malaria.

The drug appears to be compatible during breastfeeding.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

According to the World Health Organization, there were about 219 million cases of malaria and an estimated 660,000 deaths in 2010. Although huge, this was a 26% decrease from the rates in 2000. Six countries in Africa account for 47% of malaria cases: Cote d’Ivoire, Democratic Republic of the Congo, Mozambique, Nigeria, Uganda, and the United Republic of Tanzania. The second-most affected region in the world is Southeast Asia, which includes Myanmar, India, and Indonesia. In comparison, about 1,500 malaria cases and 5 deaths are reported annually in the United States, mostly from returned travelers.

Courtesy NIAID

It is extremely important for any woman that is or might be pregnant or breastfeeding to take an antimalarial drug for protection if they will be traveling in any of the above regions. Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth.

As stated by the Centers for Disease Control and Prevention, no antimalarial agent is 100% protective. Therefore, whatever agent is used must be combined with personal protective measures such as wearing insect repellent, long sleeves, and long pants; sleeping in a mosquito-free setting; or using an insecticide-treated bed net.

There are nine antimalarial drugs available in the United States.

Atovaquone/Proguanil Hcl (Malarone and as generic)

This agent is good for last-minute travelers because the drug is started 1-2 days before traveling to areas where malaria transmission occurs. The combination can be classified as compatible in pregnancy. No reports in breastfeeding with atovaquone or the combination have been found. Proguanil is not available in the United States as a single agent.

Chloroquine (generic)

This is the drug of choice to prevent and treat sensitive malaria species during pregnancy. The drug crosses the placenta producing fetal concentrations that are similar to those in the mother. The drug appears to be low risk for embryo-fetal harm.

It is compatible in breastfeeding.

Dapsone (generic)

This agent does not appear to represent a major risk of harm to the fetus. Although it has been used in combination with pyrimethamine (an antiparasitic) or trimethoprim (an antibiotic) to prevent malaria, the efficacy of the combination has not been confirmed.

In breastfeeding, there is one case of mild hemolytic anemia in the mother and her breastfeeding infant that may have been caused by the drug.

Hydroxychloroquine (generic)

This agent is used for the treatment of malaria, systemic erythematosus, and rheumatoid arthritis. For antimalarial prophylaxis, 400 mg/week appears to be low risk for embryo-fetal harm. Doses used to treat malaria have been 200-400 mg/day.

Because very low concentrations of the drug have been found in breast milk, breastfeeding is probably compatible.

Mefloquine (generic)

This agent is a quinoline-methanol agent that does not appear to cause embryo-fetal harm based on a large number of pregnancy exposures.

There are no reports of its use while breastfeeding.

Primaquine (generic)

This agent is best avoided in pregnancy. There is no human pregnancy data, but it may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Because the fetus is relatively G6PD deficient, it is best avoided in pregnancy regardless of the mother’s status.

There are no reports describing the use of the drug during lactation. Both the mother and baby should be tested for G6PD deficiency before the drug is used during breastfeeding.

Pyrimethamine (generic)

This agent has been used for the treatment or prophylaxis of malaria. Most studies have found this agent to be relatively safe and effective.

It is excreted into breast milk and has been effective in eliminating malaria parasites from breastfeeding infants.

Quinidine (generic)

Reports linking the use of this agent with congenital defects have not been found. Although the drug has data on its use as an antiarrhythmic, its published use to treat malaria is limited.

The drug is excreted into breast milk, but there are no reports of its during breastfeeding.

Quinine (generic)

This agent has a large amount of human pregnancy data (more than 1,000 exposures) that found no increased risk of birth defects. The drug has been replaced by newer agents but still may be used for chloroquine-resistant malaria.

The drug appears to be compatible during breastfeeding.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

According to the World Health Organization, there were about 219 million cases of malaria and an estimated 660,000 deaths in 2010. Although huge, this was a 26% decrease from the rates in 2000. Six countries in Africa account for 47% of malaria cases: Cote d’Ivoire, Democratic Republic of the Congo, Mozambique, Nigeria, Uganda, and the United Republic of Tanzania. The second-most affected region in the world is Southeast Asia, which includes Myanmar, India, and Indonesia. In comparison, about 1,500 malaria cases and 5 deaths are reported annually in the United States, mostly from returned travelers.

Courtesy NIAID

It is extremely important for any woman that is or might be pregnant or breastfeeding to take an antimalarial drug for protection if they will be traveling in any of the above regions. Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth.

As stated by the Centers for Disease Control and Prevention, no antimalarial agent is 100% protective. Therefore, whatever agent is used must be combined with personal protective measures such as wearing insect repellent, long sleeves, and long pants; sleeping in a mosquito-free setting; or using an insecticide-treated bed net.

There are nine antimalarial drugs available in the United States.

Atovaquone/Proguanil Hcl (Malarone and as generic)

This agent is good for last-minute travelers because the drug is started 1-2 days before traveling to areas where malaria transmission occurs. The combination can be classified as compatible in pregnancy. No reports in breastfeeding with atovaquone or the combination have been found. Proguanil is not available in the United States as a single agent.

Chloroquine (generic)

This is the drug of choice to prevent and treat sensitive malaria species during pregnancy. The drug crosses the placenta producing fetal concentrations that are similar to those in the mother. The drug appears to be low risk for embryo-fetal harm.

It is compatible in breastfeeding.

Dapsone (generic)

This agent does not appear to represent a major risk of harm to the fetus. Although it has been used in combination with pyrimethamine (an antiparasitic) or trimethoprim (an antibiotic) to prevent malaria, the efficacy of the combination has not been confirmed.

In breastfeeding, there is one case of mild hemolytic anemia in the mother and her breastfeeding infant that may have been caused by the drug.

Hydroxychloroquine (generic)

This agent is used for the treatment of malaria, systemic erythematosus, and rheumatoid arthritis. For antimalarial prophylaxis, 400 mg/week appears to be low risk for embryo-fetal harm. Doses used to treat malaria have been 200-400 mg/day.

Because very low concentrations of the drug have been found in breast milk, breastfeeding is probably compatible.

Mefloquine (generic)

This agent is a quinoline-methanol agent that does not appear to cause embryo-fetal harm based on a large number of pregnancy exposures.

There are no reports of its use while breastfeeding.

Primaquine (generic)

This agent is best avoided in pregnancy. There is no human pregnancy data, but it may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Because the fetus is relatively G6PD deficient, it is best avoided in pregnancy regardless of the mother’s status.

There are no reports describing the use of the drug during lactation. Both the mother and baby should be tested for G6PD deficiency before the drug is used during breastfeeding.

Pyrimethamine (generic)

This agent has been used for the treatment or prophylaxis of malaria. Most studies have found this agent to be relatively safe and effective.

It is excreted into breast milk and has been effective in eliminating malaria parasites from breastfeeding infants.

Quinidine (generic)

Reports linking the use of this agent with congenital defects have not been found. Although the drug has data on its use as an antiarrhythmic, its published use to treat malaria is limited.

The drug is excreted into breast milk, but there are no reports of its during breastfeeding.

Quinine (generic)

This agent has a large amount of human pregnancy data (more than 1,000 exposures) that found no increased risk of birth defects. The drug has been replaced by newer agents but still may be used for chloroquine-resistant malaria.

The drug appears to be compatible during breastfeeding.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In a head-to-head study with frozen formulations of the vaccine, refrigerator-stable varicella vaccine had comparable safety, tolerability, and immunogenicity profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.

copyright itsmejust/Thinkstock

In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.

The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.

The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.

Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.

Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.

[email protected]

SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.

In a head-to-head study with frozen formulations of the vaccine, refrigerator-stable varicella vaccine had comparable safety, tolerability, and immunogenicity profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.

copyright itsmejust/Thinkstock

In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.

The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.

The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.

Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.

Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.

[email protected]

SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.

In a head-to-head study with frozen formulations of the vaccine, refrigerator-stable varicella vaccine had comparable safety, tolerability, and immunogenicity profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.

copyright itsmejust/Thinkstock

In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.

The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.

The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.

Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.

Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.

[email protected]

SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.