Joseph N. S. Eisenberg

Seasonality of rotavirus disease in the tropics: a systematic review and meta-analysis

BACKGROUND To date little conclusive evidence exists on the seasonality of rotavirus incidence in the tropics. We present a systematic review and meta-analysis on the seasonal epidemiology of rotavirus in the tropics, including 26 studies reporting continuous monthly rotavirus incidence for which corresponding climatological data was available. METHODS Using linear regression models that account for serial correlation between months, monthly rotavirus incidence was significantly negatively correlated with temperature, rainfall and relative humidity in 65%, 55% and 60% of studies, respectively. We carried out pooled analyses using a generalized estimating equation (GEE) that accounts for correlation from between-study variation and serial correlation between months within a given study. RESULTS For every 1 degrees C (1.8 degrees F) increase in mean temperature, 1 cm (0.39 in.) increase in mean monthly rainfall, and 1% increase in relative humidity (22%) this analysis showed reductions in rotavirus incidence of 10% (95% CI: 6-13%), 1% (95% CI: 0-1%), and 3% (95% CI:0-5%), respectively. CONCLUSIONS On the basis of the evidence, we conclude that rotavirus responds to changes in climate in the tropics, with the highest number of infections found at the colder and drier times of the year.

Characterization of novel VP7, VP4, and VP6 genotypes of a previously untypeable group A rotavirus.

Rotavirus is the most common cause of acute gastroenteritis among infants and young children throughout the world, but rotavirus cases in developing countries account for nearly all of the approximately 600,000 annual deaths. We studied the epidemiology of rotavirus in 22 rural communities in northern coastal Ecuador over a five-year period. From 250 rotavirus positive stool specimens, the percentage that could not be RT-PCR genotyped for VP4 and VP7 was 77% and 63%, respectively. The possibility of sample degradation was considered but discounted after an experimental examination of rotavirus stability and EM visualization of rotavirus-like particles in several untypeable samples. Finally, alternate primers were used to amplify Ecu534, a sample that was untypeable using most published VP4 and VP7 primers. Characterization of the VP7, VP4, and VP6 full gene segments revealed novel genotypes and nucleotide mismatches with most published primer sequences. When considered with other findings, our results suggest that primer mismatch may be a widespread cause of genotyping failure, and might be particularly problematic in countries with greater rotavirus diversity. The novel sequences described in this study have been given GenBank accession numbers EU805775 (VP7), EU805773 (VP4), EU805774 (VP6) and the RCWG has assigned them novel genotypes G20P[28]I13, respectively.

Integrating disease control strategies: Balancing water sanitation and hygiene interventions to reduce diarrheal disease burden.

OBJECTIVES Although the burden of diarrheal disease resulting from inadequate water quality, sanitation practices, and hygiene remains high, there is little understanding of the integration of these environmental control strategies. We tested a modeling framework designed to capture the interdependent transmission pathways of enteric pathogens. METHODS We developed a household-level stochastic model accounting for 5 different transmission pathways. We estimated disease preventable through water treatment by comparing 2 scenarios: all households fully exposed to contaminated drinking water and all households receiving the water quality intervention. RESULTS We found that the benefits of a water quality intervention depend on sanitation and hygiene conditions. When sanitation conditions are poor, water quality improvements may have minimal impact regardless of amount of water contamination. If each transmission pathway alone is sufficient to maintain diarrheal disease, single-pathway interventions will have minimal benefit, and ultimately an intervention will be successful only if all sufficient pathways are eliminated. However, when 1 pathway is critical to maintaining the disease, public health efforts should focus on this critical pathway. CONCLUSIONS Our findings provide guidance in understanding how to best reduce and eliminate diarrheal disease through integrated control strategies.

Environmental change and infectious disease: How new roads affect the transmission of diarrheal pathogens in rural Ecuador

Environmental change plays a large role in the emergence of infectious disease. The construction of a new road in a previously roadless area of northern coastal Ecuador provides a valuable natural experiment to examine how changes in the social and natural environment, mediated by road construction, affect the epidemiology of diarrheal diseases. Twenty-one villages were randomly selected to capture the full distribution of village population size and distance from a main road (remoteness), and these were compared with the major population center of the region, Borbón, that lies on the road. Estimates of enteric pathogen infection rates were obtained from case-control studies at the village level. Higher rates of infection were found in nonremote vs. remote villages [pathogenic Escherichia coli: odds ratio (OR) = 8.4, confidence interval (CI) 1.6, 43.5; rotavirus: OR = 4.0, CI 1.3, 12.1; and Giardia: OR = 1.9, CI 1.3, 2.7]. Higher rates of all-cause diarrhea were found in Borbón compared with the 21 villages (RR = 2.0, CI 1.5, 2.8), as well as when comparing nonremote and remote villages (OR = 2.7, CI 1.5, 4.8). Social network data collected in parallel offered a causal link between remoteness and disease. The significant and consistent trends across viral, bacterial, and protozoan pathogens suggest the importance of considering a broad range of pathogens with differing epidemiological patterns when assessing the environmental impact of new roads. This study provides insight into the initial health impacts that roads have on communities and into the social and environmental processes that create these impacts.

Environmental Determinants of Infectious Disease: A Framework for Tracking Causal Links and Guiding Public Health Research

Background Discoveries that emerging and re-emerging pathogens have their origin in environmental change has created an urgent need to understand how these environmental changes impact disease burden. In this article we present a framework that provides a context from which to examine the relationship between environmental changes and disease transmission and a structure from which to unite disparate pieces of information from a variety of disciplines. Methods The framework integrates three interrelated characteristics of environment–disease relationships: a) Environmental change manifests in a complex web of ecologic and social factors that may ultimately impact disease; these factors are represented as those more distally related and those more proximally related to disease. b) Transmission dynamics of infectious pathogens mediate the effects that environmental changes have on disease. c) Disease burden is the outcome of the interplay between environmental change and the transmission cycle of a pathogen. Results To put this framework into operation, we present a matrix formulation as a means to define important elements of this system and to summarize what is known and unknown about the these elements and their relationships. The framework explicitly expresses the problem at a systems level that goes beyond the traditional risk factor analysis used in public health, and the matrix provides a means to explicitly express the coupling of different system components. Conclusion This coupling of environmental and disease transmission processes provides a much-needed construct for furthering our understanding of both specific and general relationships between environmental change and infectious disease.

An analysis of the Milwaukee cryptosporidiosis outbreak based on a dynamic model of the infection process.

We combined information on the temporal pattern of disease incidence for the 1993 cryptosporidiosis outbreak in Milwaukee with information on oocyst levels to obtain insight into the epidemic process. We constructed a dynamic process model of the epidemic with continuous population compartments using reasonable ranges for the possible distribution of the model parameters. We then explored which combinations of parameters were consistent with the observations. A poor fit of the March 1–22 portion of the time series suggested that a smaller outbreak occurred before the March 23 treatment failure, beginning sometime on or before March 1. This finding suggests that had surveillance systems detected the earlier outbreak, up to 85% of the cases might have been prevented. The same conclusion was obtained independent of the model by transforming the incidence time series data of Mac Kenzie et al.1 This transformation is based on a background monthly incidence rate for watery diarrhea in the Milwaukee area of 0.5%.1 Further analysis using the incidence data from the onset of the major outbreak, March 23, through the end of April, resulted in three inferred properties of the infection process: (1) the mean incubation period was likely to have been between 3 and 7 days; (2) there was a necessary concurrent increase in Cryptosporidium oocyst influent concentration and a decrease in treatment efficiency of the water; and (3) the variability of the dose-response function in the model did not appreciably affect the simulated outbreaks. (Epidemiology 1998;9:255–263)

Following the Water: A Controlled Study of Drinking Water Storage in Northern Coastal Ecuador

Background To design the most appropriate interventions to improve water quality and supply, information is needed to assess water contamination in a variety of community settings, including those that rely primarily on unimproved surface sources of drinking water. Objectives We explored the role of initial source water conditions as well as household factors in determining household water quality, and how levels of contamination of drinking water change over time, in a rural setting in northern coastal Ecuador. Methods We sampled source waters concurrently with water collection by household members and followed this water over time, comparing Escherichia coli and enterococci concentrations in water stored in households with water stored under controlled conditions. Results We observed significant natural attenuation of indicator organisms in control containers and significant, although less pronounced, reductions of indicators between the source of drinking water and its point of use through the third day of sampling. These reductions were followed by recontamination in approximately half of the households. Conclusions Water quality improved after water was transferred from the source to household storage containers, but then declined because of recontamination in the home. Our experimental design allowed us to observe these dynamics by controlling for initial source water quality and following changes in water quality over time. These data, because of our controlled experimental design, may explain why recontamination has been reported in the literature as less prominent in areas or households with highly contaminated source waters. Our results also suggest that efforts to improve source water quality and sanitation remain important.

Dynamics and Control of Infections Transmitted From Person to Person Through the Environment

The environment provides points for control of pathogens spread by food, water, hands, air, or fomites. These environmental transmission pathways require contact network formulations more realistically detailed than those based on social encounters or physical proximity. As a step toward improved assessment of environmental interventions, description of contact networks, and better use of environmental specimens to analyze transmission, an environmental infection transmission system model that describes the dynamics of human interaction with pathogens in the environment is presented. Its environmental parameters include the pathogen elimination rate, mu, and the rate humans pick up pathogens, rho, and deposit them, alpha. The ratio, rhoN/micro (N equals population size), indicates whether transmission is density dependent (low ratio), frequency dependent (high ratio), or in between. Transmission through frequently touched fomites, such as doorknobs, generates frequency-dependent patterns, while transmission through thoroughly mixed air or infrequently touched fomites generates density-dependent patterns. The environmental contamination ratio, alpha/gamma, reflects total agent deposition per infection and outbreak probability, where gamma is defined as the recovery rate. These insights provide theoretical contexts to examine the role of the environment in pathogen transmission and a framework to interpret environmental data to inform environmental interventions.

The joint effects of efficacy and compliance: A study of household water treatment effectiveness against childhood diarrhea

The effectiveness of household water treatment (HWT) at reducing diarrheal disease is related to the efficacy of the HWT method at removing pathogens, how people comply with HWT, and the relative contributions of other pathogen exposure routes. We define compliance with HWT as the proportion of drinking water treated by a community. Although many HWT methods are efficacious at removing or inactivating pathogens, their effectiveness within actual communities is decreased by imperfect compliance. However, the quantitative relationship between compliance and effectiveness is poorly understood. To assess the effectiveness of HWT on childhood diarrhea incidence via drinking water for three pathogen types (bacterial, viral, and protozoan), we developed a quantitative microbial risk assessment (QMRA) model. We examined the relationship between log(10) removal values (LRVs) and compliance with HWT for scenarios varying by: baseline incidence of diarrhea; etiologic fraction of diarrhea by pathogen type; pattern of compliance within a community; and size of contamination spikes in source water. Benefits from increasing LRVs strongly depend on compliance. For perfect compliance, diarrheal incidence decreases as LRVs increase. However, if compliance is incomplete, there are diminishing returns from increasing LRVs in most of the scenarios we considered. Higher LRVs are more beneficial if: contamination spikes are large; contamination levels are generally high; or some people comply perfectly. The effectiveness of HWT interventions at the community level may be limited by imperfect compliance, such that the benefits of high LRVs are not realized. Compliance with HWT should be carefully measured during HWT field studies and HWT dissemination programs. Studies of pathogen concentrations in a variety of developing-country source waters are also needed. Guidelines are needed for measuring and promoting compliance with HWT.

Heavy Rainfall Events and Diarrhea Incidence: The Role of Social and Environmental Factors

The impact of heavy rainfall events on waterborne diarrheal diseases is uncertain. We conducted weekly, active surveillance for diarrhea in 19 villages in Ecuador from February 2004 to April 2007 in order to evaluate whether biophysical and social factors modify vulnerability to heavy rainfall events. A heavy rainfall event was defined as 24-hour rainfall exceeding the 90th percentile value (56 mm) in a given 7-day period within the study period. Mixed-effects Poisson regression was used to test the hypothesis that rainfall in the prior 8 weeks, water and sanitation conditions, and social cohesion modified the relationship between heavy rainfall events and diarrhea incidence. Heavy rainfall events were associated with increased diarrhea incidence following dry periods (incidence rate ratio = 1.39, 95% confidence interval: 1.03, 1.87) and decreased diarrhea incidence following wet periods (incidence rate ratio = 0.74, 95% confidence interval: 0.59, 0.92). Drinking water treatment reduced the deleterious impacts of heavy rainfall events following dry periods. Sanitation, hygiene, and social cohesion did not modify the relationship between heavy rainfall events and diarrhea. Heavy rainfall events appear to affect diarrhea incidence through contamination of drinking water, and they present the greatest health risks following periods of low rainfall. Interventions designed to increase drinking water treatment may reduce climate vulnerability.