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In this article, we introduce a new command, clan, that conducts a cluster-level analysis of cluster randomized trials. The command simplifies adjusting for individual- and cluster-level covariates and can also account for a stratified design. It can be used to analyze a continuous, binary, or rate outcome.

Background/Objectives: Previous studies about obesity and its associated factors in low- and middle-income countries have been based mostly on women of reproductive age. Furthermore, disproportionally changing BMI distributions have been a challenge for its appropriate modeling. In this context, we assessed the magnitude and rate of change in BMI distribution by socioeconomic and geographic factors in both sexes in Latin American countries, modeling the shape of BMI distributions. Subjects/Methods: We used data from national surveys conducted in Mexico, Colombia, and Peru at two time points between 2005 and 2013 (N= 57,414, 13,5403, and 30,811, respectively). We estimated shapes of BMI distributions for 2005 and 2010, and assessed their changes, using the generalized additive model for location, scale, and shape (GAMLSS), in which BMI was assumed to follow a Box-Cox Power Exponential (BCPE) distribution. Results: In all the three countries, higher education was negatively associated with BMI in women but somewhat positive in men; and household wealth was positively associated in men but not in women. Lower household wealth was associated with higher rates of change in BMI distributions in women. Conclusion: Education and household wealth were associated with BMI distributions and their change over time. Observed sex differences in these associations have implications for designing relevant policies and programs to approach target populations effectively. The BCPE-GAMLSS method can provide a useful visual assessment of time-varying measures.

Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance.

To achieve reductions in HIV incidence, we need strategies to engage key population at risk for HIV in low-income and middle-income countries. We evaluated the effectiveness of integrated care centres in India that provided single-venue HIV testing, prevention, and treatment services for people who inject drugs (PWID) and men who have sex with men (MSM).

Children exposed to HIV have a high prevalence of stunting and anaemia. We aimed to test the effect of improved infant and young child feeding (IYCF) and improved water, sanitation, and hygiene (WASH) on child linear growth and haemoglobin concentrations.

Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general US population.

Human immunodeficiency virus (HIV) remains a major cause of pediatric morbidity in Africa. In addition, HIV-exposed, but uninfected (HEU) infants can comprise a substantial proportion of all infants born in high prevalence countries and may also be a vulnerable group with special health problems.

Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners.

Few Asian countries have introduced Haemophilus influenzaetype b (Hib) conjugate vaccine because of its cost and uncertainty regarding disease burden.

HIV causes substantial mortality among African children but there is limited data on how this is influenced by maternal or infant infection status and timing.

Background: Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men. Methods: 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984. Findings: Baseline characteristics of the men in the intervention and control groups were much the same at enrolment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up. Interpretation: Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men.

Background Most studies of Haemophilus influenzae type b (Hib) disease in Asia have found low rates, and few Asian countries use Hib vaccine in routine immunisation programmes. Whether Hib disease truly is rare or whether many cases remain undetected is unclear.Methods To estimate incidences of vaccine-preventable Hib pneumonia and meningitis among children younger than 2 years in Lombok, Indonesia, during 1998–2002, we undertook a hamlet-randomised, controlled, double-blind vaccine-probe study (818 hamlets). Children were immunised (WHO schedule) with diphtheria, tetanus, pertussis (DTP) or DTP-PRP-T (Hib conjugate) vaccine. Vaccine-preventable disease incidences were calculated as the difference in rates of clinical outcomes between DTP and DTP-PRP-T groups. Analyses included all children who received at least one vaccine dose.Findings We enrolled 55 073 children: 28 147 were assigned DTP-PRP-T and 26 926 DTP. The proportion of pneumonia outcomes prevented by vaccine ranged from less than 0 to 4·8%. Calculated incidences of vaccine-preventable Hib disease (per 105 child-years of observation) for outcome categories were: substantial alveolar consolidation or effusion, less than zero (−43 [95% CI −185 to 98]); all severe pneumonia, 264 (95% CI less than zero to 629); all clinical pneumonia, 1561 (270 to 2853); confirmed Hib meningitis, 16 (1·4 to 31); meningitis with cerebrospinal-fluid findings consistent with a bacterial aetiology, 67 (22 to 112); and admission for suspected meningitis or presenting to a clinic with convulsions, 158 (42 to 273).Interpretation Hib vaccine did not prevent the great majority of pneumonia cases, including those with alveolar consolidation. These results do not support a major role for Hib vaccine in overall pneumonia-prevention programmes. Nevertheless, the study identified high incidences of Hib meningitis and pneumonia; inclusion of Hib vaccine in routine infant immunisation programmes in Asia deserves consideration.

Recently an increase in the number of invasive Haemophilus influenzaetype b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high.

Few large studies have evaluated risk factors for mortality among children hospitalized for pneumonia and this may contribute to suboptimal case management efficiency. To identify useful screening criteria for mortality among children hospitalized for pneumonia in a developing country setting, we conducted a population-based hospital cohort study among children less than 2 years of age admitted for pneumonia during 1999-2001 at one of three major hospitals on Lombok Island, Indonesia. Of 4351 children admitted for pneumonia, 12 per cent died before discharge. Case fatality proportions were seasonal, with peaks occurring immediately after peaks in the proportion of cases positive for respiratory syncytial virus. Children with an oxygen saturation < or = 85 per cent or age younger than 4 months were 5.6 times more likely to die than children with none of these predictive factors (95 per cent CI, 4.5-7.1); 83 per cent of children who died had one of these two risk factors. For children < 4 months old, mortality increased at an oxygen saturation < 88 per cent compared with < 80 per cent for older children. Laboratory, physical examination, and radiological findings were not associated with or did not contribute substantially to mortality prediction. Among children hospitalized for pneumonia, age less than 4 months and hypoxia were identified with those at high risk of death. Age influences cut-off levels for hypoxia.

Objectives:We conducted a 4-year (1995-1998) field study in a Peruvian peri-urban community (pueblo joven) to examine the relation between diarrhea and nutritional status in 230 children <3 years of age. Methods:We followed the birth cohort daily for diarrhea and monthly for anthropometry. We modeled diarrheal incidence with a multivariate time-to-event regression model to account for multiple episodes per child and irregular follow-up periods and diarrheal duration with a mixed-effects gamma regression model to account for disease heterogeneity across children. Results:During 159,551 child-days of follow-up, we identified 1387 diarrheal episodes, which yielded an average incidence of 3.2 episodes per child-year. Diarrhea was seasonal, for example, infants had up to 8 diarrheal episodes during the summer; however, these variations decreased noticeably with age. Nutritional status was significantly associated with diarrheal incidence. The frequency of diarrhea increased by 15% per standard deviation decrease in height-for-age zscore. Diarrheal episodes in children <6 months of age lasted significantly longer than episodes among older children. Conclusions:These results identify infants and children of poor nutritional status as priority risk groups for prevention efforts aimed at reducing the burden of acute childhood diarrhea. (J Pediatr 2002;140:210-8)

Over the 33-day duration of the 1999 Haj in Saudi Arabia, we collected daily health status reports for 2070 Pakistani pilgrims over 13 years of age, 54% of whom had elected to receive influenza vaccine immediately before departing for the Haj. We calculated vaccine preventable outcome incidence as the difference in attack rates between vaccinated and unvaccinated persons. The incidences of vaccine preventable influenza-like illness (sore throat in combination with cough or fever of at least 38°C), fever, and any symptom of upper respiratory infection were 22, 17, and 24 per 100 pilgrims per Haj. For every 100 persons who attended the Haj, 17 had a course of antibiotics and 23 had a course of nonprescription cold medication that was preventable with influenza vaccine use. Influenza leads to significant morbidity and medication use among Haj pilgrims. Vaccine against influenza should be considered for pilgrims before entry into Saudi Arabia.

There have been many advances in the mapping of disease mortality and morbidity rates in recent years. An increasingly common approach is to calculate “stabilized” rates for individual geographic areas by incorporating information from the entire set of data. One such method, adopted by the National Cancer Institute for its mortality maps, is described and applied to national end-stage renal disease data. Some possible difficulties in interpretation are noted, resulting from: (1) insufficient shrinkage, (2) highly skewed rate distributions, (3) different denominator distributions, and (4) variations in population density.

Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ.

Among 453 untreated HIV-infected Zimbabwean infants, 6-week viral load was the only infant factor that independently predicted mortality. Infants with viral load ≥ 1.59 million copiesmL (cohort median) had 3-fold increased mortality through 6 months (hazard ratio 3.07 95 confidence interval: 2.16, 4.38; P< 0.001) and 2-fold increased mortality through 12 months (hazard ratio 2.03 95 confidence interval: 1.41, 2.91; P< 0.001, compared with infants with viral load below the median.

We report the phase III trial efficacy of 7-valent pneumococcal conjugate vaccine against clinical and culture proven otitis media (OM) among Navajo and White Mountain Apache infants. Efficacy was −0.4% (95% CI: −19.4 to 15.6) for clinically-diagnosed OM, 5.1% (95% CI: −51.5 to 40.6) for severe OM, and 64% (95% CI: −34% to 90%) for vaccine serotype pneumococcal OM suggesting that this vaccine is efficacious for pneumococcal OM in this high risk population.

•Behavioral training and free LPG helped participants realize the benefits of LPG.•Participants accepted perceived disadvantages of LPG given the valued benefits.•Reducing LPG costs and providing user support can facilitate near-exclusive LPG use.

The Navajo are known to be at high risk for hepatitis A virus (HAV) infection. This study investigated the safety and immunogenicity of an investigational, alum-adjuvanted, formalin-inactivated HAV vaccine (VAQTA) developed by Merck Research Laboratories in Navajo children. One hundred two of 212 children, ages 4 to 12 years, were HAV-seronegative (<10 mIU/ml by an enhanced sensitivity modification of the HAVAB; Abbott). Ninety of these children received the HAV vaccine. Study participants were given vaccines containing various viral protein concentrations: Group A (n= 18), 6 units; Group B (n= 36), 13 units; and Group C (n= 36), 25 units HAV protein (1 unit ± 1 ng viral protein antigen). Three-dose (0, 8, 24 weeks) and two-dose (0, 24 weeks) regimens were compared in subgroups within B and C. The vaccine was well-tolerated and there were no serious adverse reactions; no vaccinee developed hepatitis A. After 1 dose 82 to 100 of children seroconverted (≥10 mIU/ml, modified HAVAB; Abbott) and 100 seroconverted after 2 doses. After 1 dose the geometric mean titer for antibody was: Group A, 22 mIU/ml; Group B, 18 mIU/ml; and Group C, 38 mIU/ml. After 3 doses geometric mean titers increased to 10 106 mIU/ml in Group A, 7258 mIU/ml in Group B and 11 856 mIU/ml in Group C. Further field studies are indicated to evaluate its use in high risk populations, such as the Navajo.

OBJECTIVE:s To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery. Design Prospective cohort study. Setting Urban Zimbabwe. Participants 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001). MAIN OUTCOME MEASURES: Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period. RESULTS: Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log10copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log10copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log10copies/mL 0-30 days after infection, but rapidly declined to 2.0 log10copies/mL and <1.5 log10copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally. CONCLUSIONS: Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests. Trial registration Clinical trials.gov NCT00198718.

The degree of protection conferred by natural rotavirus infection was estimated through analyses of data gathered as part of a 2-year rotavirus vaccine study of 1185 Native American infants. In 292 placebo recipients with complete serum sample sets, rotavirus IgA antibody indicative of infection before 2 months of age was associated with a 58% decrease in symptomatic infections throughout the trial. In all 391 placebo recipients, the preventive effectiveness of an initial symptomatic infection was 72% overall and 94% within 6 months following the infection. In contrast to studies conducted at other sites in the United States, serotype G3 was the predominant serotype associated with gastrointestinal episodes (80%). The effectiveness of an initial serotype G3 episode with respect to preventing subsequent serotype G3 episodes was 91%.

Mortality was evaluated in 1972 children who had received measles vaccines at 6–11 months of age that were 10-fold (medium titer) or 100-fold (high titer) greater than standard titer. Mortality among boys did not differ by vaccine titer and was similar to mortality in children who received standard-titer vaccine. Girl recipients of high-titer vaccine had somewhat greater mortality than girls who received medium-titer vaccine (risk ratio = 1.71,95% confidence interval = 0.91–3.24). Increased mortality was associated with high-titer vaccine for girls but not for boys (P = .04). There was no evidence of selection bias or preferential health care by sex that might explain the differential mortality. This mortality pattern has been noted in two other populations with high background infant and childhood mortality. The biologic basis for this effect on mortality has not been determined. Data from this and other studies have resulted in discontinuation of the use of high-titer measles vaccines.