Daniel R. Feikin

Effect of handwashing on child health: a randomised controlled trial.

BACKGROUND More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea. METHODS In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1.2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat. FINDINGS Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap. INTERPRETATION Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.

Epidemiological differences among pneumococcal serotypes

The bacterial species Streptococcus pneumoniae consists of 90 immunologically distinct serotypes, of which some possess distinct epidemiological properties. Certain serotypes are much more likely to be associated with nasopharyngeal colonisation than to cause invasive disease. Compared with transient or infrequent colonisers, serotypes carried at high rates by young children may rapidly elicit age-associated natural immunity to invasive disease. Other serotypes seem to be of disproportionate importance as causes of disease in very young infants, in older children, in immunocompromised individuals, or in elderly people. Some serotypes seem to be associated with particular disease syndromes, such as complicated pneumonias in children, or with higher rates of hospitalisation in children or mortality in adults, or are consistently responsible for outbreaks in certain populations. Since pneumococcal conjugate vaccines are directed at specific serotypes, national immunisation advisory committees may wish to consider these serotype-specific properties when considering which vaccine formulation to introduce into a national programme.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

BACKGROUND The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING WHO; Bill & Melinda Gates Foundation.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.

Global strategies to prevent bacterial pneumonia in adults with HIV disease

We examined the peer-reviewed literature on the burden of bacterial pneumonia and the effectiveness of interventions for its prevention among HIV-infected adults in developed and developing countries. Bacterial pneumonia rates were up to 25-fold higher among HIV-infected adults than in the general community, with rates increasing as CD4+ T-cell count decreases. In developed countries, cohort studies showed that highly active antiretroviral therapy (HAART) had the most consistent effect on reducing pneumonia. In a prospective cohort and case-control studies from these regions, pneumococcal polysaccharide vaccine reduced pneumococcal disease in certain subgroups, particularly those with higher CD4+ T cells/microL. In patients with fewer than 200 CD4+ T cells/microL, antimicrobial prophylaxis was usually effective in reducing pneumonia. In sub-Saharan Africa, randomised controlled trials concluded that co-trimoxazole prophylaxis decreased rates of bacterial pneumonia, but pneumococcal polysaccharide vaccine prevented neither pneumonia nor invasive pneumococcal disease. Although not yet fully evaluated in Africa, based on experience in industrialised nations, use of HAART in Africa may have substantial potential to prevent bacterial pneumonia.

Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults.

In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with > or = 200 CD4 cells/microl received placebo (PL), 7-valent conjugate, or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate-conjugate, conjugate-polysaccharide, placebo-polysaccharide, placebo-placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders, when compared with persons receiving placebo-polysaccharide, persons receiving conjugate-conjugate and conjugate-polysaccharide had higher antibody concentrations (serotypes 4, 6B, 9V and serotype 23F, respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V, respectively) after the second dose (P<0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses.

Application of TaqMan® Low Density Arrays for Simultaneous Detection of Multiple Respiratory Pathogens

ABSTRACT The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (CT ) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.

Prevalence of antibodies against Rift Valley fever virus in Kenyan wildlife

Rift Valley fever virus (RVFV) is an arbovirus associated with periodic outbreaks, mostly on the African continent, of febrile disease accompanied by abortion in livestock, and a severe, fatal haemorrhagic syndrome in humans. However, the maintenance of the virus during the inter-epidemic period (IEP) when there is low or no disease activity detected in livestock or humans has not been determined. This study report prevalence of RVFV-neutralizing antibodies in sera (n=896) collected from 16 Kenyan wildlife species including at least 35% that were born during the 1999-2006 IEP. Specimens from seven species had detectable neutralizing antibodies against RVFV, including African buffalo, black rhino, lesser kudu, impala, African elephant, kongoni, and waterbuck. High RVFV antibody prevalence (>15%) was observed in black rhinos and ruminants (kudu, impala, buffalo, and waterbuck) with the highest titres (up to 1:1280) observed mostly in buffalo, including animals born during the IEP. All lions, giraffes, plains zebras, and warthogs tested were either negative or less than two animals in each species had low (<or= 1:16) titres of RVFV antibodies. Of 249 sera collected from five wildlife species during the 2006-2007 outbreak, 16 out of 19 (84%) of the ruminant (gerenuk, waterbuck, and eland) specimens had RVFV-neutralizing titres >or= 1:80. These data provide evidence that wild ruminants are infected by RVFV but further studies are required to determine whether these animals play a role in the virus maintenance between outbreaks and virus amplification prior to a noticeable outbreak.

Profile: The KEMRI/CDC Health and Demographic Surveillance System—Western Kenya

The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.

SERRATIA LIQUEFACIENS BLOODSTREAM INFECTIONS FROM CONTAMINATION OF EPOETIN ALFA AT A HEMODIALYSIS CENTER

BACKGROUND In a one month period, 10 Serratia liquefaciens bloodstream infections and 6 pyrogenic reactions occurred in outpatients at a hemodialysis center. METHODS We performed a cohort study of all hemodialysis sessions on days that staff members reported S. liquefaciens bloodstream infections or pyrogenic reactions. We reviewed procedures and cultured samples of water, medications, soaps, and hand lotions and swabs from the hands of personnel. RESULTS We analyzed 208 sessions involving 48 patients. In 12 sessions, patients had S. liquefaciens bloodstream infections, and in 8, patients had pyrogenic reactions without bloodstream infection. Sessions with infections or reactions were associated with higher median doses of epoetin alfa than the 188 other sessions (6500 vs. 4000 U, P=0.03) and were more common during afternoon or evening shifts than morning shifts (P=0.03). Sessions with infections or reactions were associated with doses of epoetin alfa of more than 4000 U (multivariate odds ratio, 4.0; 95 percent confidence interval, 1.3 to 12.3). A review of procedures revealed that preservative-free, single-use vials of epoetin alfa were punctured multiple times, and residual epoetin alfa from multiple vials was pooled and administered to patients. S. liquefaciens was isolated from pooled epoetin alfa, empty vials of epoetin alfa that had been pooled, antibacterial soap, and hand lotion. All the isolates were identical by pulsed-field gel electrophoresis. After the practice of pooling epoetin alfa was discontinued and the contaminated soap and lotion were replaced, no further S. liquefaciens bloodstream infections or pyrogenic reactions occurred at this hemodialysis facility. CONCLUSIONS Puncturing single-use vials multiple times and pooling preservative-free epoetin alfa caused this outbreak of bloodstream infections in a hemodialysis unit. To prevent similar outbreaks, medical personnel should follow the manufacturers guidelines for the use of preservative-free medications.