Harvey B. Lipman

Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children—implications for vaccine strategies

Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.

Risk factors for carriage of drug-resistant Streptococcus pneumoniae among children in Memphis, Tennessee

OBJECTIVES To determine risk factors for carriage of drug-resistant Streptococcus pneumoniae to understand better the factors promoting spread of these isolates. STUDY DESIGN We obtained medical and demographic information and nasopharyngeal swab specimens from 216 children less than 6 years old with upper respiratory tract infections, seeking medical care at five Memphis, Tenn, study sites. We evaluated risk factors for carriage of penicillin-nonsusceptible S. pneumoniae (NSSP) among 100 children with S. pneumoniae isolates. Patterns of antimicrobial prescription were recorded for enrolled children. RESULTS Independent risk factors for carriage of NSSP included an increased number of antimicrobial treatment courses during the previous 3 months and white race. Day care attendance approached statistical significance (p = 0.07). Most children with upper respiratory tract infection received a prescription for antimicrobial drugs. These prescriptions were more common for white children than for black children. CONCLUSIONS Increased use of antimicrobial drugs enhances the risk of carriage of NSSP. This may contribute to the higher risk among white children of NSSP infection; however, after control for antimicrobial use, white children were still at an increased risk of infection with NSSP, possibly through greater exposure to resistant strains.

High prevalence of multidrug-resistant Streptococcus pneumoniae among children in a rural Kentucky community

In 1992 drug-resistant Streptococcus pneumoniae was cultured with increasing frequency from aspirates of middle ear fluid from children with acute otitis media in a rural Kentucky community. To determine the prevalence of carriage of drug-resistant S. pneumoniae in the community, we obtained nasopharyngeal swabs from 158 (70%) of 227 children attending a child daycare center and from 82 children attending the county health center. S. pneumoniae was isolated from 126 children. Among 123 isolates tested 65 (53%) were penicillin-resistant, including 41 (33%) strains that were highly resistant; 61 (50%) were multidrug-resistant. Serotypes 19F, 6B, 23F and 6A comprised 89% of the penicillin-resistant isolates. Detection of a variety of serotypes and drug resistance patterns among nasopharyngeal isolates of S. pneumoniae suggests that multidrug-resistant pneumococcal strains are endemic in this community. Surveillance for drug-resistant pneumococci with the use of respiratory secretions obtained by nasopharyngeal swab may provide useful information on the prevalence of drug-resistant strains causing invasive disease and otitis media. Such information could be used to guide empiric therapy of pneumococcal infections.

Comparison of 3 Infrared Thermal Detection Systems and Self-Report for Mass Fever Screening

In a hospital setting, the systems had reasonable utility for fever detection.

Risk factors for nasopharyngeal carriage of resistant Streptococcus pneumoniae and detection of a multiply resistant clone among children living in the Yukon-Kuskokwim delta Region of Alaska

BACKGROUND Children < 2 years old living in the Yukon-Kuskokwim Delta (YKD) region of Alaska have one of the highest pneumococcal bacteremia rates of in the world. METHODS To determine the prevalence of and risk factors for infection with intermediate or resistant Streptococcus pneumoniae in the YKD, we cultured nasopharyngeal secretions of healthy children < or = 5 years old, reviewed their hospital records and administered questionnaires to accompanying parents. RESULTS Of 185 children evaluated we obtained 95 pneumococcal isolates; drug susceptibility patterns and serotyping results were available for 92. Of these, 33 (36%) were intermediate or resistant to at least one drug class tested; 27 isolates were intermediate (minimum inhibitory concentration 0.1 to 1.0 mg/l) and none were resistant to penicillin. Compared with other isolates, capsular serotype 6B isolates were more likely to be intermediate or resistant to at least one drug (relative risk, 5.3; P < 0.001) and to more than one drug (relative risk, 17.0; P < 0.001). The majority of 6B isolates had identical pneumococcal surface protein A patterns. Carriage of intermediate or resistant pneumococcus was associated with age < 2 years (relative risk, 3.0; P < 0.001) but not with antibiotic use or other evaluated risk factors. CONCLUSIONS Young age but not antibiotic use was associated with carriage of intermediate or resistant S. pneumoniae in the YKD region of Alaska. Much of the intermediate or resistant pneumococcus in the YKD may have resulted from the proliferation of a single capsular serotype 6B clone.

Likely transmission of norovirus on an airplane, October 2008.

BACKGROUND On 8 October 2008, members of a tour group experienced diarrhea and vomiting throughout an airplane flight from Boston, Massachusetts, to Los Angeles, California, resulting in an emergency diversion 3 h after takeoff. An investigation was conducted to determine the cause of the outbreak, assess whether transmission occurred on the airplane, and describe risk factors for transmission. METHODS Passengers and crew were contacted to obtain information about demographics, symptoms, locations on the airplane, and possible risk factors for transmission. Case patients were defined as passengers with vomiting or diarrhea (> or =3 loose stools in 24 h) and were asked to submit stool samples for norovirus testing by real-time reverse-transcription polymerase chain reaction. RESULTS Thirty-six (88%) of 41 tour group members were interviewed, and 15 (41%) met the case definition (peak date of illness onset, 8 October 2008). Of 106 passengers who were not tour group members, 85 (80%) were interviewed, and 7 (8%) met the case definition after the flight (peak date of illness onset, 10 October 2008). Multivariate logistic regression analysis showed that sitting in an aisle seat (adjusted relative risk, 11.0; 95% confidence interval, 1.4-84.9) and sitting near any tour group member (adjusted relative risk, 7.5; 95% confidence interval, 1.7-33.6) were associated with the development of illness. Norovirus genotype II was detected by reverse-transcription polymerase chain reaction in stool samples from case patients in both groups. CONCLUSIONS Despite the short duration, transmission of norovirus likely occurred during the flight.

Non-Pharmaceutical Interventions during an Outbreak of 2009 Pandemic Influenza A (H1N1) Virus Infection at a Large Public University, April–May 2009

Nonpharmaceutical interventions (NPIs), such as home isolation, social distancing, and infection control measures, are recommended by public health agencies as strategies to mitigate transmission during influenza pandemics. However, NPI implementation has rarely been studied in large populations. During an outbreak of 2009 Pandemic Influenza A (H1N1) virus infection at a large public university in April 2009, an online survey was conducted among students, faculty, and staff to assess knowledge of and adherence to university-recommended NPI. Although 3924 (65%) of 6049 student respondents and 1057 (74%) of 1401 faculty respondents reported increased use of self-protective NPI, such as hand washing, only 27 (6.4%) of 423 students and 5 (8.6%) of 58 faculty with acute respiratory infection (ARI) reported staying home while ill. Nearly one-half (46%) of student respondents, including 44.7% of those with ARI, attended social events. Results indicate a need for efforts to increase compliance with home isolation and social distancing measures.

Effectiveness of a school district closure for pandemic influenza A (H1N1) on acute respiratory illnesses in the community: a natural experiment

BACKGROUND Following detection of pandemic influenza A H1N1 (pH1N1) in Dallas/Fort Worth, Texas, a school district (intervention community, [IC]) closed all public schools for 8 days to reduce transmission. Nearby school districts (control community [CC]) mostly remained open. METHODS We collected household data to measure self-reported acute respiratory illness (ARI), before, during, and after school closures. We also collected influenza-related visits to emergency departments (ED(flu)). RESULTS In both communities, self-reported ARIs and ED(flu) visits increased from before to during the school closure, but the increase in ARI rates was 45% lower in the IC (0.6% before to 1.2% during) than in the CC (0.4% before to 1.5% during) (RRR(During)(/Before) = 0.55, P < .001; adjusted OR(During/Before) = 0.49, P < .03). For households with school-aged children only (no children 0-5 years), IC had even lower increases in adjusted ARI than in the CC (adjusted OR(During/Before) = 0.28, P < .001). The relative increase of total ED(flu) visits in the IC was 27% lower (2.8% before to 4.4% during) compared with the CC (2.9% before to 6.2% during). Among children aged 6-18 years, the percentage of ED(flu) in IC remained constant (5.1% before vs 5.2% during), whereas in the CC it more than doubled (5.2% before vs 10.9% during). After schools reopened, ARI rates and ED(flu) visits decreased in both communities. CONCLUSIONS Our study documents a reduction in ARI and ED(flu) visits in the intervention community. Our findings can be used to assess the potential benefit of school closures during pandemics.

A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

We evaluated whether coadministration of the yellow fever (YF) virus vaccine with human immunoglobulin (Ig) that contained YF virus-neutralizing antibodies would reduce post-vaccination viremia without compromising immunogenicity and thus, potentially mitigate YF vaccine-associated adverse events. We randomized 80 participants to receive either YF vaccine and Ig or YF vaccine and saline placebo. Participants were followed for 91 days for safety and assessments of viremia and immunogenicity. There were no differences found between the two groups in the proportion of vaccinated participants who developed viremia, seroconversion, cluster of differentiation (CD)-8(+) and CD4(+) T-cell responses, and cytokine responses. These results argue against one putative explanation for the increased reporting of YF vaccine side effects in recent years (i.e., a change in travel clinic practice after 1996 when hepatitis A prophylaxis with vaccine replaced routine use of pre-travel Ig, thus potentially removing an incidental YF vaccine-attenuating effect of anti-YF virus antibodies present in Ig).

Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007-June 2008.

INTRODUCTION Contact investigations conducted in the United States of persons with tuberculosis (TB) who traveled by air while infectious have increased. However, data about transmission risks of Mycobacterium tuberculosis on aircraft are limited. METHODS We analyzed data on index TB cases and passenger contacts from contact investigations initiated by the U.S. Centers for Disease Control and Prevention from January 2007 through June 2008. RESULTS Contact investigations for 131 index cases met study inclusion criteria, including 4550 passenger contacts. U.S. health departments reported TB screening test results for 758 (22%) of assigned contacts; 182 (24%) had positive results. Of the 142 passenger contacts with positive TB test results with information about risk factors for prior TB infection, 130 (92%) had at least one risk factor and 12 (8%) had no risk factors. Positive TB test results were significantly associated with risk factors for prior TB infection (OR 23; p<0.001). No cases of TB disease among passenger contacts were reported. CONCLUSION The risks of M. tuberculosis transmission during air travel remain difficult to quantify. Definitive assessment of transmission risks during flights and determination of the effectiveness of contact-tracing efforts will require comprehensive cohort studies.