Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Assessing the Health Impact of Water Quality Interventions in Low-Income Settings: Concerns Associated with Blinded Trials and the Need for Objective Outcomes.

BACKGROUND: A dramatic disparity between the results of blinded versus open trial designs has raised questions about the effectiveness of water quality interventions and other environmental interventions to prevent diarrhea, a leading killer of young children in low-income countries. OBJECTIVES: We summarize the results of blinded versus open trials of water quality interventions, describe evidence from a recent placebo-controlled trial in India suggesting that control households were put at risk from their participation, and suggest alternatives to blinded trials that could resolve continued uncertainty about the magnitude of the protective effect of water, sanitation, and hygiene (WASH) interventions without presenting ethical questions. DISCUSSION: Concerns about reporting bias in open trial designs continue to cause uncertainty about the effectiveness of WASH interventions. However, evidence suggests that despite instructions to the contrary, placebos may encourage control group participants in blinded trials to cease practicing traditional water treatment practices in the mistaken belief that they are protected by an active intervention. Although objective outcomes such as pathogen incrimination, seroconversion, biomarkers, and anthropometry can be helpful, these are often costly, nonspecific, and unsuitable for evaluating programmatic interventions. CONCLUSIONS: Unless researchers can be assured that a placebo will not cause those in a control group to change their behavior in a manner that increases their risk, it is incumbent on researchers to use alternatives. Validated objective measures are needed for assessing the health impact of WASH interventions that are reliable, affordable, and suitable both for research and program evaluation. CITATION: Clasen T, Boisson S. 2016. Assessing the health impact of water quality interventions in low-income settings: concerns associated with blinded trials and the need for objective outcomes. Environ Health Perspect 124:886-889; http://dx.doi.org/10.1289/ehp.1510532

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135287/1/wnan1403.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135287/2/wnan1403_am.pd

Low Sensitivity of T-Cell Based Detection of Tuberculosis among HIV Co-Infected Tanzanian In-Patients

Objective: To evaluate the performance of QuantiFERON-TB GOLD (QFTG) in a resource-poor setting among patients with and without HIV infection.Design: Cross-sectional study.Setting: Two hospitals in Northern Tanzania.Subjects: Eighty three adult male and female inpatients.Intervention: All patients were screened for HIV infection and underwent tuberculin skin test (TST) and QFTG.Results: Eighty-three subjects were enrolled, and 29 (35%) of 83 were HIV-infected. QFTG yielded indeterminate results in 12 (22%; 95%CI 12%-34%) of 54 HIV-uninfected and 13 (45%; 95%CI 26%-64%) of 29 HIV-infected subjects (p=0.0323). Among those with smear-positive pulmonary tuberculosis, TST was positive in 40 (100%; 95%CI 91%-100%) of 40 HIV-uninfected subjects compared with seven (54%; 95%CI 25%- 81%) of 13 HIV-infected subjects (p<0.0001), and QFTG was positive in 28(70%; 95%CI 53%-83%) of 40 HIV-uninfected subjects compared with three (23%; 95%CI 5%-54%) of 13 HIV-infected subjects (p=0.0029). Among medical inpatients at risk for latent tuberculosis infection, TST was positive in seven (50%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p=0.0701) and QFTG was positive among two (14%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p=0.7437).Conclusions: The presence of HIV co-infection was associated with a significant reduction in sensitivity of both the TST (p<0.0001) and QFTG (p=0.0029) for the diagnosis of active M.tuberculosis infection. The high proportion of indeterminate QFTG and lack of sensitivity, particularly among HIV-infected patients, may limit its applicability in settings like Tanzania. Larger studies in resource-poor settings are required.

Global burden of human brucellosis : a systematic review of disease frequency

BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understand of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources

Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa

Background: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were.15-fold higher than rates in the rural site for the same age group

Environmental foundations of typhoid fever in the Fijian residential setting

Proximal characteristics and conditions in the residential setting deserve greater attention for their potential to influence typhoid transmission. Using a case-control design in Central Division, Republic of Fiji, we examined bacterial (coliform and Escherichia coli) contamination and chemical composition of water and soil as potential vehicles of exposure to Salmonella Typhi, combining observational analysis of residential living conditions, geospatial analysis of household locations, and factor analysis to explore multivariate associations with the risk of developing typhoid fever. Factors positively associated with typhoid infection related to drainage [phosphate (OR 4.235, p = 0.042) and E. coli concentrations (OR 2.248, p = 0.029) in toilet drainage soil, housing [external condition (OR 3.712, p \u3c 0.001)], drinking water contamination (OR 2.732, p = 0.003) and sanitary condition (OR 1.973, p = 0.031). These five factors explained 42.5% of the cumulative variance and were significant in predicting typhoid infection. Our results support the hypothesis that a combination of spatial and biophysical attributes of the residential setting influence the probability of typhoid transmission; in this study, factors associated with poor drainage, flooding, and sanitary condition increase local exposure to contaminated water and soil, and thereby infection. These findings extend testing of causal assumptions beyond the immediate domestic domain, enhance the scope of traditional case control epidemiology and allow greater specificity of interventions at the scale of the residential setting

Structure and Function of the α-Hydroxylation Bimodule of the Mupirocin Polyketide Synthase

\ua9 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.Mupirocin is a clinically important antibiotic produced by a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens. The major bioactive metabolite, pseudomonic acid A (PA−A), is assembled on a tetrasubstituted tetrahydropyran (THP) core incorporating a 6-hydroxy group proposed to be introduced by α-hydroxylation of the thioester of the acyl carrier protein (ACP) bound polyketide chain. Herein, we describe an in vitro approach combining purified enzyme components, chemical synthesis, isotopic labelling, mass spectrometry and NMR in conjunction with in vivo studies leading to the first characterisation of the α-hydroxylation bimodule of the mupirocin biosynthetic pathway. These studies reveal the precise timing of hydroxylation by MupA, substrate specificity and the ACP dependency of the enzyme components that comprise this α-hydroxylation bimodule. Furthermore, using purified enzyme, it is shown that the MmpA KS0 shows relaxed substrate specificity, suggesting precise spatiotemporal control of in trans MupA recruitment in the context of the PKS. Finally, the detection of multiple intermodular MupA/ACP interactions suggests these bimodules may integrate MupA into their assembly