Intensity and frequency of extreme novel epidemics.

Observational knowledge of the epidemic intensity, defined as the number of deaths divided by global population and epidemic duration, and of the rate of emergence of infectious disease outbreaks is necessary to test theory and models and to inform public health risk assessment by quantifying the probability of extreme pandemics such as COVID-19. Despite its significance, assembling and analyzing a comprehensive global historical record spanning a variety of diseases remains an unexplored task. A global dataset of historical epidemics from 1600 to present is here compiled and examined using novel statistical methods to estimate the yearly probability of occurrence of extreme epidemics. Historical observations covering four orders of magnitude of epidemic intensity follow a common probability distribution with a slowly decaying power-law tail (generalized Pareto distribution, asymptotic exponent = -0.71). The yearly number of epidemics varies ninefold and shows systematic trends. Yearly occurrence probabilities of extreme epidemics, Py, vary widely: Py of an event with the intensity of the "Spanish influenza" (1918 to 1920) varies between 0.27 and 1.9% from 1600 to present, while its mean recurrence time today is 400 y (95% CI: 332 to 489 y). The slow decay of probability with epidemic intensity implies that extreme epidemics are relatively likely, a property previously undetected due to short observational records and stationary analysis methods. Using recent estimates of the rate of increase in disease emergence from zoonotic reservoirs associated with environmental change, we estimate that the yearly probability of occurrence of extreme epidemics can increase up to threefold in the coming decades.

CystiHuman: A model of human neurocysticercosis.

INTRODUCTION: The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. METHODS: This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. RESULTS AND DISCUSSION: Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence.

A prospective cohort study linking migration, climate, and malaria risk in the Peruvian Amazon.

Migration is an important risk factor for malaria transmission for malaria transmission, creating networks that connect Plasmodium between communities. This study aims to understand the timing of why people in the Peruvian Amazon migrated and how characteristics of these migrants are associated with malaria risk. A cohort of 2,202 participants was followed for three years (July 2006 - October 2009), with thrice-weekly active surveillance to record infection and recent travel, which included travel destination(s) and duration away. Migration occurred more frequently in the dry season, but the 7-day rolling mean (7DRM) streamflow was positively correlated with migration events (OR 1.25 (95% CI: 1.138, 1.368)). High-frequency and low-frequency migrant populations reported 9.7 (IRR 7.59 (95% CI:.381, 13.160)) and 4.1 (IRR 2.89 (95% CI: 1.636, 5.099)) times more P. vivax cases than those considered non-migrants and 30.7 (IRR 32.42 (95% CI: 7.977, 131.765)) and 7.4 (IRR 7.44 (95% CI: 1.783, 31.066)) times more P. falciparum cases, respectively. High-frequency migrants employed in manual labour within their community were at 2.45 (95% CI: 1.113, 5.416) times higher risk than non-employed low-frequency migrants. This study confirms the importance of migration for malaria risk as well as factors increasing risk among the migratory community, including, sex, occupation, and educational status.

Government interventions and control policies to contain the first COVID-19 outbreak: An analysis of evidence.

BACKGROUND: The overarching aim of this study was to evaluate the effectiveness over time of government interventions and policy restrictions and the impact of determinants on spread and mortality during the first-wave of the COVID-19 pandemic, globally, regionally and by country-income level, up to 18 May 2020. METHODS: We created a global database merging World Health Organization daily case reports (from 218 countries/territories) with other socio-demographic and population health measures from 21 January to 18 May 2020. A four-level government policy interventions score (low to very high) was created based on the Oxford Stringency Index. RESULTS: Our results support the use of very high government interventions to suppress both COVID-19 spread and mortality effectively during wave one globally compared to other policy levels of control. Similar trends in virus propagation and mortality were observed in all country-income levels and specific regions. CONCLUSIONS: Rapid implementation of government interventions was needed to contain the first wave of the COVID-19 outbreak and to reduce COVID-19-related mortality.

Estimating the COVID-19 Spread Through Real-time Population Mobility Patterns: Surveillance in Low- and Middle-Income Countries.

BACKGROUND: On January 21, 2020, the World Health Organization reported the first case of severe acute respiratory syndrome coronavirus 2, which rapidly evolved to the COVID-19 pandemic. Since then, the virus has also rapidly spread among Latin American, Caribbean, and African countries. OBJECTIVE: The first aim of this study is to identify new emerging COVID-19 clusters over time and space (from January 21 to mid-May 2020) in Latin American, Caribbean, and African regions, using a prospective space-time scan measurement approach. The second aim is to assess the impact of real-time population mobility patterns between January 21 and May 18, 2020, under the implemented government interventions, measurements, and policy restrictions on COVID-19 spread among those regions and worldwide. METHODS: We created a global COVID-19 database, of 218 countries and territories, merging the World Health Organization daily case reports with other measures such as population density and country income levels for January 21 to May 18, 2020. A score of government policy interventions was created for low, intermediate, high, and very high interventions. The population's mobility patterns at the country level were obtained from Google community mobility reports. The prospective space-time scan statistic method was applied in five time periods between January and May 2020, and a regression mixed model analysis was used. RESULTS: We found that COVID-19 emerging clusters within these five periods of time increased from 7 emerging clusters to 28 by mid-May 2020. We also detected various increasing and decreasing relative risk estimates of COVID-19 spread among Latin American, Caribbean, and African countries within the period of analysis. Globally, population mobility to parks and similar leisure areas during at least a minimum of implemented intermediate-level control policies (when compared to low-level control policies) was related to accelerated COVID-19 spread. Results were almost consistent when regional stratified analysis was applied. In addition, worldwide population mobility due to working during high implemented control policies and very high implemented control policies, when compared to low-level control policies, was related to positive COVID-19 spread. CONCLUSIONS: The prospective space-time scan is an approach that low-income and middle-income countries could use to detect emerging clusters in a timely manner and implement specific control policies and interventions to slow down COVID-19 transmission. In addition, real-time population mobility obtained from crowdsourced digital data could be useful for current and future targeted public health and mitigation policies at a global and regional level.

Deforestation Due to Artisanal and Small-Scale Gold Mining Exacerbates Soil and Mercury Mobilization in Madre de Dios, Peru.

Artisanal and small-scale gold mining (ASGM) is a significant contributor of mercury (Hg) contamination and deforestation across the globe. In the Colorado River watershed in Madre de Dios, Peru, mining and deforestation have increased exponentially since the 1980s, resulting in major socioeconomic shifts in the region and two national state of emergency (2016 and 2019) in response to concerns for wide-scale mercury poisoning by these activities. This research employed a watershed-scale soil particle detachment model and environmental field sampling to estimate the role of land cover change and soil erosion on river transport of Hg in a heavily ASGM-impacted watershed. The model estimated that observed decreases in forest cover increased soil mobilization by a factor of two in the Colorado River watershed during the 18 year period and by 4-fold in the Puquiri subwatershed (the area of most concentrated ASGM activity). If deforestation continues to increase at its current exponential rate through 2030, the annual mobilization of soil and Hg may increase by an additional 20-25% relative to 2014 levels. While, the estimated total mass of Hg transported by rivers is substantially less than the estimated tons of Hg used with ASGM in Peru, this research shows that deforestation associated with ASGM is an additional mechanism for mobilizing naturally occurring and anthropogenic Hg from terrestrial landscapes to aquatic environments in the region, potentially leading to bioaccumulation in fish and exposure to communities downstream.

Population-based dietary exposure to mercury through fish consumption in the Southern Peruvian Amazon.

BACKGROUND: Mercury exposure related to artisanal and small-scale gold mining (ASGM) has raised environmental and public health concerns globally. Exposure to mercury, a potent neurotoxin that bioaccumulates in fish, is especially of concern to women of childbearing age (WCBA) and children in high-fish consuming populations. In Madre de Dios (MDD), Peru, an Amazon region with naturally occurring mercury and high ASGM activity, there is significant exposure concern among the mainly riverine, fish-consuming communities. The objective of this study was to conduct the first assessment of mercury exposure in a population-based sample of MDD, identify factors associated with elevated levels and compare the relationship between fish consumption and hair total mercury (H-THg) among persons living in ASGM affected and non-ASGM affected watersheds. METHODS: Hair samples and household demographic surveys, including a module on fish consumption, were collected from 723 participants across 46 communities within 10 km of the Interoceanic Highway in MDD, who were previously enrolled in the first population-based study in MDD spanning areas affected and unaffected by ASGM. H-THg concentration (natural log transformed) was evaluated for association with independent demographic variables through multilevel multivariate regression models accounting for clustering among households and communities. Samples from canned fish available at local stores were also tested for total mercury. RESULTS: Fish consumption (diversity and total consumed) varied spatially along the highway. 269 participants (37.2%) had elevated H-THg (>2.2 µg/g; median 1.60 µg/g; mean 2.24 µg/g), including 42.7% of WCBA and 20.0% of children under 5. Overall, H-THg was higher among people living in ASGM-affected areas. H-THg concentrations were strongly associated with fish consumption; however, in the multivariate models, household consumption of high trophic level fish was associated with elevated H-THg only in communities located in the ASGM-impacted watersheds. Similarly, the relationship between living in a household engaged in economic activities of fishing or Brazil nut harvesting was associated with higher H-THg, but only among households in the ASGM-affected area. In the non-ASGM affected areas, we observed a positive relationship between household daily fruit consumption and H-THg that was not observed in ASGM-affected areas. CONCLUSION: Diet, residential location, and occupation are strong predictors of mercury exposure in Madre de Dios, Peru. Canned fish may represent a previously overlooked source of dietary Hg exposure in the region. In accordance with the Minamata Convention on Mercury, the significant environmental health concern of mercury exposure in ASGM areas demands policy and programmatic attention.

Enteroaggregative Escherichia coli Subclinical Infection and Coinfections and Impaired Child Growth in the MAL-ED Cohort Study.

OBJECTIVE: We evaluated the impact of subclinical enteroaggregative Escherichia coli (EAEC) infection alone and in combination with other pathogens in the first 6 months of life on child growth. METHODS: Nondiarrheal samples from 1684 children across 8 Multisite Birth Cohort Study, Malnutrition and Enteric Diseases (MAL-ED) sites in Asia, Africa, and Latin America were tested monthly; more than 90% of children were followed-up twice weekly for the first 6 months of life. RESULTS: Children with subclinical EAEC infection did not show altered growth between enrollment and 6 months. Conversely, EAEC coinfection with any other pathogen was negatively associated with delta weight-for-length (P < 0.05) and weight-for-age (P > 0.05) z scores between 0 and 6 months. The presence of 2 or more pathogens without EAEC was not significantly associated with delta weight-for-length and weight-for-age. The most frequent EAEC coinfections included Campylobacter spp, heat-labile toxin-producing enterotoxigenic E coli, Cryptosporidium spp, and atypical enteropathogenic E coli. Myeloperoxidase levels were increased with EAEC coinfection (P < 0.05). EAEC pathogen codetection was associated with lower neopterin levels compared to those of no-pathogen control children (P < 0.05). Mothers of children with EAEC coinfections had lower levels of education, poorer hygiene and sanitation, lower socioeconomic status, and lower breast-feeding rates compared to mothers of children in whom no pathogen was detected (P < 0.05). CONCLUSIONS: These data emphasize the public health importance of subclinical EAEC infection in early infancy in association with other pathogens and the need for improved maternal and child care, hygiene, sanitation, and socioeconomic factors.

Nitrogen Affects Wheat and Canola Silica Accumulation, Soil Silica Forms, and Crusting.

Raindrop-induced crusting of mineral soils supporting wheat ( L.) in the semiarid US Pacific Northwest reduces seedling establishment of late summer-seeded winter crops during dry, hot conditions. Canola ( L.) integration is diversifying regional food, feed and fuel global markets. Subsequent shifts in recycled crop residue characteristics, including Si and crop fiber, may shift soil characteristics of traditional wheat-dominated systems, potentially affecting their propensity to form soil crusts. In a greenhouse study, wheat and canola were fertilized with varying N rates. Increased N supply increased transpiration, shoot weight, and hemicellulose and cellulose yields, but with only minor increases in shoot Si and lignin yields. Both crops had similar increases in root Si with greater N-stimulated transpiration. Two subsequent soil incubations were conducted to determine how Si, N fertilization, and crop residues from wheat and canola affected soil properties. In the first incubation, Si was applied as aqueous HSiO, which increased soil amorphous and water-soluble Si (Si and Si), physical resistance, and crust thickness. Electron micrographs showed increased amorphous material, presumably a Si precipitate, on soil particles with increased Si application. Second, two Ritzville soils were treated with the canola or wheat shoot residues with and without N fertilizer. Nitrogen lowered soil pH, Si, Si, surface resistance, and crust thickness; however, first-time application of crop residue types had no short-term effect on these parameters. Any impacts of lower Si returned by lower Si crop residues on soil physical properties likely require several rotational cycles of Si crop uptake and residue returns.

Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa.

BACKGROUND: Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. METHODS: We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. RESULTS: Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54-11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40-3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. CONCLUSIONS: HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients.

Antagonistic Growth Effects of Mercury and Selenium in Caenorhabditis elegans Are Chemical-Species-Dependent and Do Not Depend on Internal Hg/Se Ratios.

The relationship between mercury (Hg) and selenium (Se) toxicity is complex, with coexposure reported to reduce, increase, and have no effect on toxicity. Different interactions may be related to chemical compound, but this has not been systematically examined. Our goal was to assess the interactive effects between the two elements on growth in the nematode Caenorhabditis elegans, focusing on inorganic and organic Hg (HgCl2 and MeHgCl) and Se (selenomethionine, sodium selenite, and sodium selenate) compounds. We utilized aqueous Hg/Se dosing molar ratios that were either above, below, or equal to 1 and measured the internal nematode total Hg and Se concentrations for the highest concentrations of each Se compound. Observed interactions were complicated, differed between Se and Hg compounds, and included greater-than-additive, additive, and less-than-additive growth impacts. Biologically significant interactions were only observed when the dosing Se solution concentration was 100-25,000 times greater than the dosing Hg concentration. Mitigation of growth impacts was not predictable on the basis of internal Hg/Se molar ratio; improved growth was observed at some internal Hg/Se molar ratios both above and below 1. These findings suggest that future assessments of the Hg and Se relationship should incorporate chemical compound into the evaluation.

Is There a Relationship Between the Concentration of Same-Sex Couples and Tobacco Retailer Density?

BACKGROUND: Tobacco use is markedly higher among lesbian, gay, and bisexual populations than heterosexuals. Higher density of tobacco retailers is found in neighborhoods with lower income and more racial/ethnic minorities. Same-sex couples tend to live in similar neighborhoods, but the association of this demographic with tobacco retailer density has not been examined. METHODS: For a national sample of 97 US counties, we calculated the number of tobacco retailers per 1000 persons and rates of same-sex couples per 1000 households in each census tract (n = 17 941). Using spatial regression, we examined the association of these variables in sex-stratified models, including neighborhood demographics and other environmental characteristics to examine confounding. RESULTS: Results from spatial regression show that higher rates of both female and male same-sex couples were associated with a higher density of tobacco retailers. However the magnitude of this association was small. For female couples, the association was not significant after controlling for area-level characteristics, such as percent black, percent Hispanic, median household income, the presence of interstate highways, and urbanicity, which are neighborhood correlates of higher tobacco retailer density. For male couples, the association persisted after control for these characteristics. CONCLUSION: Same-sex couples reside in areas with higher tobacco retailer density, and for men, this association was not explained by neighborhood confounders, such as racial/ethnic composition and income. While lesbian, gay, and bisexual disparities in tobacco use may be influenced by neighborhood environment, the magnitude of the association suggests other explanations of these disparities remain important areas of research.

Towards sustainable partnerships in global health: the case of the CRONICAS Centre of Excellence in Chronic Diseases in Peru.

Human capital requires opportunities to develop and capacity to overcome challenges, together with an enabling environment that fosters critical and disruptive innovation. Exploring such features is necessary to establish the foundation of solid long-term partnerships. In this paper we describe the experience of the CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia in Lima, Peru, as a case study for fostering meaningful and sustainable partnerships for international collaborative research. The CRONICAS Centre of Excellence in Chronic Diseases was established in 2009 with the following Mission: "We support the development of young researchers and collaboration with national and international institutions. Our motivation is to improve population's health through high quality research." The Centre's identity is embedded in its core values - generosity, innovation, integrity, and quality- and its trajectory is a result of various interactions between multiple individuals, collaborators, teams, and institutions, which together with the challenges confronted, enables us to make an objective assessment of the partnership we would like to pursue, nurture and support. We do not intend to provide a single example of a successful partnership, but in contrast, to highlight what can be translated into opportunities to be faced by research groups based in low- and middle-income countries, and how these encounters can provide a strong platform for fruitful and sustainable partnerships. In defiant contexts, partnerships require to be nurtured and sustained. Acknowledging that all partnerships are not and should not be the same, we also need to learn from the evolution of such relationships, its key successes, hurdles and failures to contribute to the promotion of a culture of global solidarity where mutual goals, mutual gains, as well as mutual responsibilities are the norm. In so doing, we will all contribute to instil a new culture where expectations, roles and interactions among individuals and their teams are horizontal, the true nature of partnerships.

Land use as a mediating factor of fertility in the Amazon.

Despite implications for both humans and the environment, a scant body of research examines fertility in forest frontiers. This study examines the fertility-environment association using empirical data from Ecuadorian Amazon between 1980 and 1999. Fertility dramatically declined during this period, and our empirical models suggest that households' relationship to land partially explains this decline. Controlling for known fertility determinants such as age and education, women in households lacking land titles experienced a 27 % higher birth rate than did women in households with land titles. This suggests insecure land tenure was associated with higher fertility. Furthermore, each additional hectare of new pasture was associated with a 16 % higher birth rate, suggesting the potential role of a more stable and lucrative income source in supporting additional births. Findings from this research can help inform strategic policies to address sustainable development in frontier environments.

Genotypic and Spatial Analysis of Mycobacterium tuberculosis Transmission in a High-Incidence Urban Setting.

BACKGROUND: Genotyping Mycobacterium tuberculosis isolates allows study of dynamics of tuberculosis transmission, while geoprocessing allows spatial analysis of clinical and epidemiological data. Here, genotyping data and spatial analysis were combined to characterize tuberculosis transmission in Vitória, Brazil, to identify distinct neighborhoods and risk factors associated with recent tuberculosis transmission. METHODS: From 2003 to 2007, 503 isolates were genotyped by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping. The analysis included kernel density estimation, K-function analysis, and a t test distance analysis. Mycobacterium tuberculosis isolates belonging to identical RFLP patterns (clusters) were considered to represent recent tuberculosis infection (cases). RESULTS: Of 503 genotyped isolates, 242 (48%) were categorized into 70 distinct clusters belonging to 12 RFLP families. The proportion of recent transmission was 34.2%. Kernel density maps indicated 3 areas of intense concentration of cases. K-function analysis of the largest RFLP clusters and families showed they co-localized in space. The distance analysis confirmed these results and demonstrated that unique strain patterns (controls) randomly distributed in space. A logit model identified young age, positive smear test, and lower Index of Quality of Urban Municipality as risk factors for recent transmission. The predicted probabilities for each neighborhood were mapped and identified neighborhoods with high risk for recent transmission. CONCLUSIONS: Spatial and genotypic clustering of M. tuberculosis isolates revealed ongoing active transmission of tuberculosis caused by a small subset of strains in specific neighborhoods of the city. Such information provides an opportunity to target tuberculosis transmission control, such as through rigorous and more focused contact investigation programs.

A validated agent-based model to study the spatial and temporal heterogeneities of malaria incidence in the rainforest environment.

BACKGROUND: The Amazon environment has been exposed in the last decades to radical changes that have been accompanied by a remarkable rise of both Plasmodium falciparum and Plasmodium vivax malaria. The malaria transmission process is highly influenced by factors such as spatial and temporal heterogeneities of the environment and individual-based characteristics of mosquitoes and humans populations. All these determinant factors can be simulated effectively trough agent-based models. METHODS: This paper presents a validated agent-based model of local-scale malaria transmission. The model reproduces the environment of a typical riverine village in the northern Peruvian Amazon, where the malaria transmission is highly seasonal and apparently associated with flooding of large areas caused by the neighbouring river. Agents representing humans, mosquitoes and the two species of Plasmodium (P. falciparum and P. vivax) are simulated in a spatially explicit representation of the environment around the village. The model environment includes: climate, people houses positions and elevation. A representation of changes in the mosquito breeding areas extension caused by the river flooding is also included in the simulation environment. RESULTS: A calibration process was carried out to reproduce the variations of the malaria monthly incidence over a period of 3 years. The calibrated model is also able to reproduce the spatial heterogeneities of local scale malaria transmission. A "what if" eradication strategy scenario is proposed: if the mosquito breeding sites are eliminated through mosquito larva habitat management in a buffer area extended at least 200 m around the village, the malaria transmission is eradicated from the village. CONCLUSIONS: The use of agent-based models can reproduce effectively the spatiotemporal variations of the malaria transmission in a low endemicity environment dominated by river floodings like in the Amazon.

Methods of analysis of enteropathogen infection in the MAL-ED Cohort Study.

Studies of diarrheal etiology in low- and middle-income countries have typically focused on children presenting with severe symptoms to health centers and thus are best equipped to describe the pathogens capable of leading to severe diarrheal disease. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study was designed to evaluate, via intensive community surveillance, the hypothesis that repeated exposure to enteropathogens has a detrimental effect on growth, vaccine response, and cognitive development, which are the primary outcome measures for this study. In the setting of multiple outcomes of interest, a longitudinal cohort design was chosen. Because many or even the majority of enteric infections are asymptomatic, the collection of asymptomatic surveillance stools was a critical element. However, capturing diarrheal stools additionally allowed for the determination of the principle causes of diarrhea at the community level as well as for a comparison between those enteropathogens associated with diarrhea and those that are associated with poor growth, diminished vaccine response, and impaired cognitive development. Here, we discuss the analytical methods proposed for the MAL-ED study to determine the principal causes of diarrhea at the community level and describe the complex interplay between recurrent exposure to enteropathogens and these critical long-term outcomes.

Evaluating associations between vaccine response and malnutrition, gut function, and enteric infections in the MAL-ED cohort study: methods and challenges.

Most vaccine assessments have occurred in well-nourished populations of higher socioeconomic status. However, vaccines are often used in populations with high incidences of malnutrition and infections, in whom the effectiveness of some vaccines is inferior for unknown reasons. The degree and extent of vaccine underperformance have not been systematically studied for most vaccines across differing epidemiologic settings. This paper outlines the methods used and challenges associated with measuring immunological responses to oral vaccines against poliovirus and rotavirus, and parenteral vaccines against pertussis, tetanus, and measles in an observational study that monitored daily illness, monthly growth, intestinal inflammation and permeability, pathogen burden, dietary intake, and micronutrient status in children in 8 countries. This evaluation of vaccine response in the context of low- and middle-income countries is intended to address the gaps in knowledge of the heterogeneity in vaccine response in diverse epidemiological settings and the interplay between infections, nutrition, and immune response.

Tuberculosis among health care workers in KwaZulu-Natal, South Africa: a retrospective cohort analysis.

BACKGROUND: Tuberculosis (TB) is an occupational hazard for health care workers (HCWs) who are at greater risk of developing TB than the general population. The objective of this study was to compare the difference in TB incidence among HCWs with versus without a history of working in TB wards, to estimate the incidence of TB among HCWs, and to identify risk factors for TB disease in HCWs. METHODS: A retrospective cohort study (January 2006 to December 2010) was conducted in three district hospitals in KwaZulu-Natal, South Africa. Data were abstracted via chart review from occupational health medical records. Bivariate and multivariate analyses were performed using a Poisson multilevel mixed model. RESULTS: Of 1,313 (92%) medical charts reviewed with data on location of work documented, 112 (9%) cases of TB were identified. Among HCWs with TB 14 (13%) had multidrug-resistant TB. Thirty-six (32%) were cured, 33 (29%) completed treatment, and 13 (12%) died. An increased incidence of TB was reported for HCWs with a history of working in TB wards (incidence rate ratio [IRR] 2.03, 95% CI 1.11-3.71), pediatric wards (IRR 1.82 95% CI 1.07-3.10), outpatient departments (IRR 2.08 95% CI 1.23-3.52), and stores/workshop (IRR 2.38 95% CI 1.06-5.34) compared with those without such a history. HCWs living with HIV had a greater incidence of TB (IRR 3.2, 95% CI 1.54-6.66) than HIV-negative HCWs. TB incidence among HCWs was approximately two-fold greater than that of the general population over the study period. CONCLUSIONS: HCWs working in a TB ward had an increased incidence of TB. However, a greater incidence of TB was also found in HCWs working in other wards including pediatric wards, outpatient departments and stores. We also identified a greater incidence of TB among HCWs than the general population. These findings further support the need for improved infection control measures not only in TB or drug-resistant TB wards or areas perceived to be at high-risk but also throughout hospitals to protect HCWs. Additionally, it is recommended for occupational health services to routinely screen HCWs for TB and provide HCWs with access to care for TB and HIV.