A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.

Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Primary antimicrobial resistance among Mycobacterium tuberculosis isolates from HIV seropositive and HIV seronegative patients in Dar es Salaam Tanzania

The United Republic of Tanzania is one of the 22 high M. tuberculosis burden countries. Data collected between 2002 and 2007 indicate that the global prevalence of drug-resistant M. tuberculosis including MDR vary greatly. The varied drug-resistance patterns make continuous surveillance of drug resistance an essential component of tuberculosis control program. M. tuberculosis isolates were obtained from consenting adult tuberculosis patients involved in a placebo-controlled study to evaluate the efficacy of multivitamin supplements on response to anti-Tb treatment in Dar es Salaam, Tanzania. Antimicrobial susceptibility testing was done on four antimicrobial agents namely streptomycin, isoniazid, ethambutol and rifampicin. HIV testing and CD4+ T lymphocytes enumeration were also done. A total of 280 M. tuberculosis isolates from 191 (68%) males and 89 (32%) female patients with no previous history of anti-tuberculosis treatment exceeding 4 weeks in the previous 12 months were tested. Among these, 133 (47%) patients were HIV seropositive. Fourteen (5.0%) isolates were resistant to any of the anti-tuberculosis drugs. The prevalence of primary resistance was 5.0%, 0.7%, 0.4% and 0% for isoniazid, streptomycin, rifampicin and ethambutol respectively. One isolate (0.4%) was MDR, with resistance to isoniazid, streptomycin and rifampicin. M. Tb primary resistance rate in a selected population in Dar es Salaam Tanzania is low and efforts should be undertaken to support the Tuberculosis program

Serological Protection 5-6 Years Post Vaccination Against Yellow Fever in African Infants Vaccinated in Routine Programmes.

Introduction: Although effective live attenuated yellow fever (YF) vaccines have been available for over 9 decades sporadic outbreaks continue to occur in endemic regions. These may be linked to several factors including epidemiological factors such as vector and intermediate host distribution or vaccine coverage and efficacy. The World Health Organization's research priorities include gathering systematic evidence around the potential need for booster vaccination with YF vaccine whether this follows full or fractional doses in children. Knowledge on the longevity of response to YF vaccine and the implications of this response needs to be consolidated to guide future vaccination policy. Methods: We measured anti-YF IgG by microneutralization assay in a group of 481 African infants who had received YF vaccine as part of routine EPI programmes, to explore serological protection from YF 5-6 years post YF vaccination, as well as the effect of co variates. Findings: Notably, 22.2% of the cohort had undetectable antibody concentrations, with another 7.5% revealing concentrations below the threshold of seropositivity of 0.5 IU/mL. Sex, season, country and time since vaccination did not affect the longevity of antibody concentration or having antibody concentrations above a defined threshold. Conclusion: Roughly 30% of children in this cohort did not demonstrate anti-yellow fever antibody concentrations above the defined threshold of protection, with 20% having no demonstrable antibody. Knowledge on the longevity of response to YF vaccine and the implications needs to be consolidated to guide future vaccination policy

High Seroprevalence for Typhus Group rickettsiae, southwestern Tanzania.

Rickettsioses caused by typhus group rickettsiae have been reported in various African regions. We conducted a cross-sectional survey of 1,227 participants from 9 different sites in the Mbeya region, Tanzania; overall seroprevalence of typhus group rickettsiae was 9.3%. Risk factors identified in multivariable analysis included low vegetation density and highway proximity

Predictors of stillbirth among HIV-infected Tanzanian women

Objective: To determine maternal risk factors for stillbirth among pregnant HIV-infected women in sub-Saharan Africa. Design: Prospective cohort study nested within a micronutrient trial. At enrollment, maternal sociodemographic, obstetric, immunologic, clinical, and nutritional variables were measured. Women were followed through monthly clinic visits until delivery. Multivariate predictors of stillbirth were identified in Poisson regression models. Setting: Antenatal clinic in a tertiary care hospital in urban Dar es Salaam, Tanzania. Population: N = 1,078 women enrolled between 12 and 27 weeks of gestation. Main outcome measures: Stillbirth (delivery of dead baby ≥ 28 weeks’ gestation), fresh stillbirth, and macerated stillbirth. Results: Among 1,017 singleton pregnancies, there were 49 stillbirths, yielding a stillbirth risk of 50.0 per 1,000 deliveries (95% Confidence Interval(CI) = 37.2, 65.6). Of stillbirths with known type, 53.7% were fresh and 46.3% macerated. In multivariate analyses, baseline measures of late ( ≥ 21 weeks’ gestation) study entry (Relative Risk (RR) = 2.13, 95% CI = 1.17, 3.87), CD3 count ≥ 1,179 cells/ml (RR = 2.15, 95% CI = 1.16, 4.01), stillbirth history (RR = 3.53, 95% CI = 1.30, 9.59), primiparity (RR = 3.65, 95% CI = 1.83, 7.29), and syphilis infection (RR = 2.06, 95% CI = 1.09, 3.88) predicted increased stillbirth risk. Late study entry, illiteracy, stillbirth history, primiparity, CD3 count ≥ 1,179 cells/ml, gonorrhea infection, and previous hospitalization predicted increased risk of fresh stillbirth, while living alone and syphilis infection predicted increased risk of macerated stillbirth. Conclusions: Applying antenatal screening and preventive tools for the socioeconomic, obstetric, immunologic, and clinical risk factors identified may assist in reducing the high incidence of stillbirth among HIV-infected women in urban sub-Saharan Africa

Increased and Expedited Case Detection by Xpert MTB/RIF Assay in Childhood Tuberculosis: A Prospective Cohort Study

The Xpert MTB/RIF assay is a quick and accurate tuberculosis diagnostic tool in children. Compared with microscopy, 3-fold more tuberculosis cases were detected with a similar turnaround time, resulting in a potentially shortened time to tuberculosis diagnosi

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Background Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation. Methodology/Principal findings Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DR(pos)CD38(pos) CD4 T cells and effector memory cells CD4 T cells (CD45RO(pos)CD27(neg)) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections. Conclusions/Significance W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis

Background Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)–infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Results Micronutrients decreased the risk of TB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, −14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Conclusions Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Ascaris lumbricoides Infection and Its Relation to Environmental Factors in the Mbeya Region of Tanzania, a Cross-Sectional, Population-Based Study

Background: With one quarter of the world population infected, the intestinal nematode Ascaris lumbricoides is one of the most common infectious agents, especially in the tropics and sub-tropics. Infection is caused by oral intake of eggs and can cause respiratory and gastrointestinal problems. To identify high risk areas for intervention, it is necessary to understand the effects of climatic, environmental and socio-demographic conditions on A. lumbricoides infection. Methodology: Cross-sectional survey data of 6, 366 study participants in the Mbeya region of South-Western Tanzania were used to analyze associations between remotely sensed environmental data and A. lumbricoides infection. Non-linear associations were accounted for by using fractional polynomial regression, and socio-demographic and sanitary data were included as potential confounders. Principal Findings: The overall prevalence of A. lumbricoides infection was 6.8%. Our final multivariable model revealed a significant non-linear association between rainfall and A. lumbricoides infection with peak prevalences at 1740 mm of mean annual rainfall. Mean annual land surface temperature during the day was linearly modeled and negatively associated with A. lumbricoides infection (odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.78-0.97). Furthermore, age, which also showed a significant non-linear association (infection maximum at 7.7 years),socio-economic status (OR = 0.82, CI = 0.68-0.97),and latrine coverage around the house (OR = 0.80, CI = 0.67-0.96) remained in the final model. Conclusions: A. lumbricoides infection was associated with environmental, socio-demographic and sanitary factors both in uni-and multivariable analysis. Non-linear analysis with fractional polynomials can improve model fit, resulting in a better understanding of the relationship between environmental conditions and helminth infection, and more precise predictions of high prevalence areas. However, socio-demographic determinants and sanitary conditions should also be considered, especially when planning public health interventions on a smaller scale, such as the community level

Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19)

Background: Due to the SARS-CoV-2 pandemic, public health interventions have been introduced globally in order to prevent the spread of the virus and avoid the overload of health care systems, especially for the most severely affected patients. Scientific studies to date have focused primarily on describing the clinical course of patients, identifying treatment options and developing vaccines. In Germany, as in many other regions, current tests for SARS-CoV2 are not conducted on a representative basis and in a longitudinal design. Furthermore, knowledge about the immune status of the population is lacking. Nonetheless, these data are needed to understand the dynamics of the pandemic and hence to appropriately design and evaluate interventions. For this purpose, we recently started a prospective population-based cohort in Munich, Germany, with the aim to develop a better understanding of the state and dynamics of the pandemic. Methods: In 100 out of 755 randomly selected constituencies, 3000 Munich households are identified via random route and offered enrollment into the study. All household members are asked to complete a baseline questionnaire and subjects ≥14 years of age are asked to provide a venous blood sample of ≤3 ml for the determination of SARS-CoV-2 IgG/IgA status. The residual plasma and the blood pellet are preserved for later genetic and molecular biological investigations. For twelve months, each household member is asked to keep a diary of daily symptoms, whereabouts and contacts via WebApp. If symptoms suggestive for COVID-19 are reported, family members, including children < 14 years, are offered a pharyngeal swab taken at the Division of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich, for molecular testing for SARS-CoV-2. In case of severe symptoms, participants will be transferred to a Munich hospital. For one year, the study teams re-visits the households for blood sampling every six weeks. Discussion: With the planned study we will establish a reliable epidemiological tool to improve the understanding of the spread of SARS-CoV-2 and to better assess the effectiveness of public health measures as well as their socio-economic effects. This will support policy makers in managing the epidemic based on scientific evidence