William Pan

Natural Ventilation for the Prevention of Airborne Contagion

Background Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. Methods and Findings The study was carried out in eight hospitals in Lima, Peru; five were hospitals of “old-fashioned” design built pre-1950, and three of “modern” design, built 1970–1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. Conclusions Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.

The Infectiousness of Tuberculosis Patients Coinfected with HIV

Background The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB. Methods and Findings All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour. Conclusions A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.

Changes in Population and Land Use Over Time in the Ecuadorian Amazon.

This paper draws upon a detailed longitudinal survey of households living on agricultural plots in the northern three provinces of the Ecuadorian Amazon, the principal region of colonization by migrants in Ecuador since the 1970s. Following the discovery of petroleum in 1967 near what has subsequently come to be the provincial capital and largest Amazonian city of Lago Agrio, oil companies built roads to lay pipelines to extract and pump oil across the Andes for export. As a result, for the past 30 years over half of both Ecuadors export earnings and government revenues have come from petroleum extracted from this region. But the roads also facilitated massive spontaneous in-migration of families from origin areas in the Ecuadorian Sierra, characterized by minifundia and rural poverty. This paper is about those migrants and their effects on the Amazonian landscape. We discuss the data collection methodology and summarize key results on settler characteristics and changes in population, land use, land ownership, technology, labor allocation, and living conditions, as well as the relationships between changes in population and changes in land use over time. The population in the study region has been growing rapidly due to both natural population growth (high fertility) and in-migration. This has led to a dramatic process of subdivision and fragmentation of plots in the 1990s, which contrasts with the consolidation of plots that has occurred in most of the mature frontier areas of the Brazilian Amazon. This fragmentation has led to important changes in land tenure and land use, deforestation, cattle raising, labor allocation, and settler welfare.

Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence

Background Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access. Methods We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status. Results Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55–5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05). Conclusions In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed.

Diagnosis of Cystic Echinococcosis, Central Peruvian Highlands

High prevalence was confirmed by ultrasonography, radiography, and 2 serologic tests, although usefulness of serologic testing in the field was limited.

Infant and Child Mortality in India in the Last Two Decades: A Geospatial Analysis

Background Studies examining the intricate interplay between poverty, female literacy, child malnutrition, and child mortality are rare in demographic literature. Given the recent focus on Millennium Development Goals 4 (child survival) and 5 (maternal health), we explored whether the geographic regions that were underprivileged in terms of wealth, female literacy, child nutrition, or safe delivery were also grappling with the elevated risk of child mortality; whether there were any spatial outliers; whether these relationships have undergone any significant change over historical time periods. Methodology The present paper attempted to investigate these critical questions using data from household surveys like NFHS 1992–1993, NFHS 1998–1999 and DLHS 2002–2004. For the first time, we employed geo-spatial techniques like Morans-I, univariate LISA, bivariate LISA, spatial error regression, and spatiotemporal regression to address the research problem. For carrying out the geospatial analysis, we classified India into 76 natural regions based on the agro-climatic scheme proposed by Bhat and Zavier (1999) following the Census of India Study and all estimates were generated for each of the geographic regions. Result/Conclusions This study brings out the stark intra-state and inter-regional disparities in infant and under-five mortality in India over the past two decades. It further reveals, for the first time, that geographic regions that were underprivileged in child nutrition or wealth or female literacy were also likely to be disadvantaged in terms of infant and child survival irrespective of the state to which they belong. While the role of economic status in explaining child malnutrition and child survival has weakened, the effect of mothers education has actually become stronger over time.

Epidemiology of Highly Endemic Multiply Antibiotic-Resistant Shigellosis in Children in the Peruvian Amazon

OBJECTIVE. Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes. PATIENTS AND METHODS. We conducted a 43-month-long prospective, community-based diarrheal disease surveillance in 442 children <72 months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006. RESULTS. The incidence of diarrheal disease was 4.38 episodes per child-year. The incidence rate for shigellosis was 0.34 episodes per child-year in children <72 months of age and peaked in children between 12 and 23 months at 0.43 episodes per child-year. Maternal education at or beyond the primary grade level, piped water supply, weight-for-age z score, and improved water-storage practices were the most significant determinants of disease in this community with living conditions comparable to many rural areas in the developing world. CONCLUSIONS. Children living in this region had a 20-fold higher rate of disease incidence detected by active surveillance as those recently estimated by passive detection. Most symptomatic disease was caused by S flexneri, although the diversity of serotypes will require a multivalent vaccine to have a significant impact on the burden of disease caused by shigellosis. Several other public health disease-control interventions targeted at water source and improved storage, nutritional interventions, and improved maternal education seem to have a greater impact than a univalent S flexneri 2a vaccine.

Symptomatic and asymptomatic Campylobacter infections associated with reduced growth in Peruvian children.

Background Although diarrheal illnesses are recognized as both a cause and effect of undernutrition, evidence for the effect of specific enteropathogens on early childhood growth remains limited. We estimated the effects of undernutrition as a risk factor for campylobacteriosis, as well as associations between symptomatic and asymptomatic Campylobacter infections and growth. Methodology/Principal Findings Using data from a prospective cohort of 442 children aged 0–72 months, the effect of nutritional status on the incidence of Campylobacter infection was estimated using uni- and multivariate Poisson models. Multivariate regression models were developed to evaluate the effect of Campylobacter infection on weight gain and linear growth. Overall, 8.3% of diarrheal episodes were associated with Campylobacter (crude incidence rate = 0.37 episodes/year) and 4.9% of quarterly asymptomatic samples were Campylobacter positive. In univariate models, the incidence of Campylobacter infection was marginally higher in stunted than non-stunted children (IRR 1.270, 95% CI (0.960, 1.681)(p = 0.095). When recent diarrheal burdens were included in the analysis, there was no difference in risk between stunted and unstunted children. Asymptomatic and symptomatic Campylobacter infections were associated with reduced weight gain over a three-month period (65.5 g (95% CI: −128.0, −3.0)(p = 0.040) and 43.9 g (95% CI:−87.6, −1.0)(p = 0.049) less weight gain, respectively). Symptomatic Campylobacter infections were only marginally associated with reduced linear growth over a nine month period (−0.059 cm per episode, 95% CI: −0.118, 0.001)(p = 0.054), however relatively severe episodes were associated with reduced linear growth (−0.169 cm/episode, 95% CI −0.310, −0.028)(p = 0.019). Conclusions/Significance Our findings suggest that Campylobacter is not as benign as commonly assumed, and that there is evidence to support expanding the indications for antibiotic therapy in campylobacteriosis in children.

Vaccine knowledge and practices of primary care providers of exempt vs. vaccinated children

Objectives: Compare vaccine knowledge, attitudes, and practices of primary care providers for fully vaccinated children and children who are exempt from school immunization requirements. Methods: We conducted a mailed survey of parent-identified primary care providers from four states to measure perceived risks and benefits of vaccination and other key immunization beliefs. Frequencies of responses were stratified by type of provider, identified by exempt versus vaccinated children. Logistic regression was used to calculate odds ratios for responses by provider type. Results: 551 surveys were completed (84.3% response rate). Providers for exempt children had similar attitudes to providers for non-exempt children. However, there were statistically significant increased concerns among providers for exempt children regarding vaccine safety and lack of perceived individual and community benefits for vaccines compared to other providers. Conclusions: The great majority of providers for exempt children had similar attitudes about vaccine safety, effectiveness, and benefits as providers of non-exempt children. Although providers for exempt children were more likely to believe that multiple vaccines weaken a child’s immune system and were concerned about vaccine safety and less likely to consider vaccines were beneficial, a substantial proportion of providers of both exempt and vaccinated children have concerns about vaccine safety and believe that CDC underestimates the frequency of vaccine side effects. Effective continuing education of providers about the risks and benefits of immunization and including in vaccine recommendations more information on pre and post licensing vaccine safety evaluations may overcome some of these perceptions.

Comparative effects of vivax malaria, fever and diarrhoea on child growth.

BACKGROUND The adverse impact of Plasmodium vivax on child health beyond acute febrile illness is poorly studied. The effect of vivax malaria on child growth was evaluated and compared with diarrhoeal disease and non-specific fever. METHODS Using data from a 43-month longitudinal cohort of children 0-72 months of age (n = 442) in the Peruvian Amazon, ponderal and linear growth velocities over 2-, 4- and 6-month periods were examined using longitudinal models and related to the incidence of disease during the same period. RESULTS An episode of vivax malaria led to 138.6 g (95% confidence interval (CI) 81.9-195.4), 108.6 g (62.8-153.2) and 61 g (20.9-101.1) less weight gain over 2-, 4- and 6-month intervals, respectively. These deficits were larger than both diarrhoea (21.9, 17.2 and 13.8 g less weight gain, respectively) and fever (39.0, 30.3 and 25.6 g less weight gain, respectively). An incident episode of vivax also led to 0.070 cm (0.004-0.137) and 0.083 cm (0.015-0.151) less linear growth over 4 and 6 months, respectively, which were also larger than deficits from diarrhoea (0.029 and 0.028 cm, respectively) and fever (not associated with linear growth deficits). Despite the larger effect of P. vivax incident episodes on growth of a particular child, diarrhoeal disease had a larger cumulative impact on growth deficits as diarrhoeal incidence rates in this community are >10-fold higher than vivax malaria. CONCLUSIONS Disease control measures for vivax malaria and diarrhoeal disease have the potential to improve the growth of children in endemic areas.