William Checkley

Effects of El Nino and ambient temperature on hospital admissions for diarrhoeal diseases in Peruvian children

INTRODUCTION To investigate whether the El Niño phenomenon and ambient temperature had an effect on the epidemiology of childhood diarrhoea, we analysed data on daily number of admissions of children with diarrhoea to the Oral Rehydration Unit of the Instituto de Salud del Niño in Lima, Peru, between January, 1993, and November, 1998. METHODS We obtained daily data on hospital admissions from the Oral Rehydration Unit, and meteorological data from the Peruvian Weather Service, and used time-series linear regression models to assess the effects of the 1997-98 El Niño event on admissions for diarrhoea. FINDINGS 57,331 children under 10 years old were admitted to the unit during the study. During the 1997-98 El Niño episode, mean ambient temperature in Lima increased up to 5 degrees C above normal, and the number of daily admissions for diarrhoea increased to 200% of the previous rate. 6225 excess admissions were attributable to El Niño, and these cost US

Multi-country analysis of the effects of diarrhoea on childhood stunting

277,000. During the period before the El Niño episode, admissions for diarrhoea increased by 8% per 1 degree C increase in mean ambient temperature. The effects of El Niño and ambient temperature on the number of admissions for diarrhoea were greatest during the winter months. INTERPRETATION El Niño had an effect on hospital admissions greater than that explained by the regular seasonal variability in ambient temperature. The excess increase in ambient temperature was the main environmental variable affecting admissions. If our findings are reproducible in other regions, diarrhoeal diseases may increase by millions of cases worldwide with each degree of increase in ambient temperature above normal.

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Diarrhoea is an important cause of death and illness among children in developing countries; however, it remains controversial as to whether diarrhoea leads to stunting. We conducted a pooled analysis of nine studies that collected daily diarrhoea morbidity and longitudinal anthropometry to determine the effects of the longitudinal history of diarrhoea prior to 24 months on stunting at age 24 months. Data covered a 20-year period and five countries. We used logistic regression to model the effect of diarrhoea on stunting. The prevalence of stunting at age 24 months varied by study (range 21-90%), as did the longitudinal history of diarrhoea prior to 24 months (incidence range 3.6-13.4 episodes per child-year, prevalence range 2.4-16.3%). The effect of diarrhoea on stunting, however, was similar across studies. The odds of stunting at age 24 months increased multiplicatively with each diarrhoeal episode and with each day of diarrhoea before 24 months (all P < 0.001). The adjusted odds of stunting increased by 1.13 for every five episodes (95% CI 1.07-1.19), and by 1.16 for every 5% unit increase in longitudinal prevalence (95% CI 1.07-1.25). In this assembled sample of 24-month-old children, the proportion of stunting attributed to >or=5 diarrhoeal episodes before 24 months was 25% (95% CI 8-38%) and that attributed to being ill with diarrhoea for >or=2% of the time before 24 months was 18% (95% CI 1-31%). These observations are consistent with the hypothesis that a higher cumulative burden of diarrhoea increases the risk of stunting.

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

Effect of water and sanitation on childhood health in a poor Peruvian peri-urban community

CONTEXT The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge. OBJECTIVE To determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA. DESIGN, SETTING, AND PARTICIPANTS Cohort study of 19,833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA. MAIN OUTCOME MEASURE Time from age at entry until age at death from any cause. RESULTS In 137,819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45). CONCLUSION Detection of MRSA in the respiratory tract of CF patients was associated with worse survival.

Beyond mortality: Future clinical research in acute lung injury

BACKGROUND Inadequate water and sanitation adversely affect the health of children in developing countries. We aimed to assess the effects of water and sanitation on childhood health in a birth cohort of Peruvian children. METHODS We followed up children once a day for diarrhoea and once a month for anthropometry, and obtained data for household water and sanitation at baseline. FINDINGS At 24 months of age, children with the worst conditions for water source, water storage, and sanitation were 1.0 cm (95% CI 0.1-0.8) shorter and had 54% (-1 to 240) more diarrhoeal episodes than did those with the best conditions. Children from households with small storage containers had 28% (1-63) more diarrhoeal episodes than did children from households with large containers. Lack of adequate sewage disposal explained a height deficit of 0.9 cm (0.2-1.7) at 24 months of age. Better water source alone did not accomplish full health benefits. In 24-month-old children from households with a water connection, those in households without adequate sewage disposal and with small storage containers were 1.8 cm (0.1-3.6) shorter than children in households with sewage and with large storage containers. INTERPRETATION Our findings show that nutritional status is a useful endpoint for water and sanitation interventions and underscores the need to improve sanitation in developing countries. Improved and more reliable water sources should discourage water storage at risk of becoming contaminated, decrease diarrhoeal incidence, and improve linear growth in children.

Maternal Vitamin A Supplementation and Lung Function in Offspring

Mortality in National Heart, Lung and Blood Institute-sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines. The workshop assessed the current state of clinical research addressing ALI, identified research needs, and recommended: (1) continued performance of trials evaluating treatments of patients with ALI; (2) development of strategies to perform ALI prevention trials; (3) observational studies of patients without ALI undergoing prolonged mechanical ventilation; and (4) development of a standardized format for reporting methods, endpoints, and results of ALI trials.

Epidemiologic differences between cyclosporiasis and cryptosporidiosis in Peruvian children.

BACKGROUND Vitamin A is important in regulating early lung development and alveolar formation. Maternal vitamin A status may be an important determinant of embryonic alveolar formation, and vitamin A deficiency in a mother during pregnancy could have lasting adverse effects on the lung health of her offspring. We tested this hypothesis by examining the long-term effects of supplementation with vitamin A or beta carotene in women before, during, and after pregnancy on the lung function of their offspring, in a population with chronic vitamin A deficiency. METHODS We examined a cohort of rural Nepali children 9 to 13 years of age whose mothers had participated in a placebo-controlled, double-blind, cluster-randomized trial of vitamin A or beta-carotene supplementation between 1994 and 1997. RESULTS Of 1894 children who were alive at the end of the original trial, 1658 (88%) were eligible to participate in the follow-up trial. We performed spirometry in 1371 of the children (83% of those eligible) between October 2006 and March 2008. Children whose mothers had received vitamin A had a forced expiratory volume in 1 second (FEV(1)) and a forced vital capacity (FVC) that were significantly higher than those of children whose mothers had received placebo (FEV(1), 46 ml higher with vitamin A; 95% confidence interval [CI], 6 to 86; FVC, 46 ml higher with vitamin A; 95% CI, 8 to 84), after adjustment for height, age, sex, body-mass index, calendar month, caste, and individual spirometer used. Children whose mothers had received beta carotene had adjusted FEV(1) and FVC values that were similar to those of children whose mothers had received placebo (FEV(1), 14 ml higher with beta carotene; 95% CI, -24 to 54; FVC, 17 ml higher with beta carotene, 95% CI, -21 to 55). CONCLUSIONS In a chronically undernourished population, maternal repletion with vitamin A at recommended dietary levels before, during, and after pregnancy improved lung function in offspring. This public health benefit was apparent in the preadolescent years.

Lung ultrasound for the diagnosis of pneumonia in children: a meta-analysis.

We compared the epidemiologic characteristics of cyclosporiasis and cryptosporidiosis in data from a cohort study of diarrhea in a periurban community near Lima, Peru. Children had an average of 0.20 episodes of cyclosporiasis/year and 0.22 episodes of cryptosporidiosis/year of follow-up. The incidence of cryptosporidiosis peaked at 0.42 for 1-year-old children and declined to 0.06 episodes/child-year for 5- to 9-year-old children. In contrast, the incidence of cyclosporiasis was fairly constant among 1- to 9-year-old children (0.21 to 0.28 episodes/child-year). Likelihood of diarrhea decreased significantly with each episode of cyclosporiasis; for cryptosporidiosis, this trend was not statistically significant. Both infections were more frequent during the warm season (December to May) than the cooler season (June to November). Cryptosporidiosis was more frequent in children from houses without a latrine or toilet. Cyclosporiasis was associated with ownership of domestic animals, especially birds, guinea pigs, and rabbits.

Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community

BACKGROUND AND OBJECTIVE: Pneumonia is the leading cause of death of children. Diagnostic tools include chest radiography, but guidelines do not currently recommend the use of lung ultrasound (LUS) as a diagnostic method. We conducted a meta-analysis to summarize evidence on the diagnostic accuracy of LUS for childhood pneumonia. METHODS: We performed a systematic search in PubMed, Embase, the Cochrane Library, Scopus, Global Health, World Health Organization–Libraries, and Latin American and Caribbean Health Sciences Literature of studies comparing LUS diagnostic accuracy against a reference standard. We used a combination of controlled key words for age <18 years, pneumonia, and ultrasound. We identified 1475 studies and selected 15 (1%) for further review. Eight studies (765 children) were retrieved for analysis, of which 6 (75%) were conducted in the general pediatric population and 2 (25%) in neonates. Eligible studies provided information to calculate sensitivity, specificity, and positive and negative likelihood ratios. Heterogeneity was assessed by using Q and I2 statistics. RESULTS: Five studies (63%) reported using highly skilled sonographers. Overall methodologic quality was high, but heterogeneity was observed across studies. LUS had a sensitivity of 96% (95% confidence interval [CI]: 94%–97%) and specificity of 93% (95% CI: 90%–96%), and positive and negative likelihood ratios were 15.3 (95% CI: 6.6–35.3) and 0.06 (95% CI: 0.03–0.11), respectively. The area under the receiver operating characteristic curve was 0.98. Limitations included the following: most studies included in our analysis had a low number of patients, and the number of eligible studies was also small. CONCLUSIONS: Current evidence supports LUS as an imaging alternative for the diagnosis of childhood pneumonia. Recommendations to train pediatricians on LUS for diagnosis of pneumonia may have important implications in different clinical settings.