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Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period. Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae. [ABSTRACT FROM AUTHOR]

Background: Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology: A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings: The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion: Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure. [ABSTRACT FROM AUTHOR]

Background: Anemia is a major public health problem that adversely affects pregnancy outcomes. The prevalence of anemia among pregnant women before conception is not well known in Tanzania. The aim of this study was to determine the prevalence, types, and risk factors of preconception anemia in women of reproductive age from a rural Tanzanian setting. Methods: Trained field workers visited households to identify all female residents aged 18–40 years and invited them to the nearby health facility for screening and enrolment into this study. Baseline samples were collected to measure hemoglobin levels, serum ferritin, vitamin B12, folate, C-reactive protein, alanine amino-transferase, the presence of malaria, HIV, and soil transmitted helminth infections. Anthropometric and socio-economic data were recorded alongside with clinical information of participants. Logistic regression analysis was used to determine the adjusted odds ratios (AOR) for the factors associated with preconception anemia. Findings: Of 1248 women enrolled before conception, 36.7% (95% confidence interval (CI) 34.1–39.4) had anemia (hemoglobin <12 g/dL) and 37.6% (95% CI 34.9–40.4) had iron deficiency. For more than half of the anemic cases, iron deficiency was also diagnosed (58.8%, 95% CI 54.2–63.3). Anemia was independently associated with increased age (AOR 1.05, 95% CI 1.03–1.07), malaria infection at enrolment (AOR 2.21, 95% CI 1.37–3.58), inflammation (AOR 1.77, 95% CI 1.21–2.60) and iron deficiency (AOR 4.68, 95% CI 3.55–6.17). The odds of anemia were reduced among women with increased mid-upper arm circumference (AOR 0.90, 95% CI 0.84–0.96). Conclusion: Anemia among women of reproductive age before conception was prevalent in this rural setting. Increased age, iron deficiency, malaria infection and inflammation were significant risk factors associated with preconception anemia, whereas increased mid-upper arm circumference was protective against anemia. Interventions to ensure adequate iron levels as well as malaria control before conception are needed to prevent anemia before and during pregnancy and improve birth outcomes in this setting. Trial registration: . [ABSTRACT FROM AUTHOR]

Background: In recent years, evidence of Rift Valley fever (RVF) transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. Methodology: A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV) was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. Findings: An overall seroprevalence of 11.3% (n = 1680) was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158) whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p<0.001). Animals living >15 km from the flood plain were more likely to have antibodies than those living <5 km (OR 1.92; 95% CI 1.04–3.56). Species, breed, herd composition, grazing practices and altitude were not associated with seropositivity. Conclusion: These findings indicate post-epidemic transmission of RVFV in the study area. The linear increase in seroprevalence in the post-epidemic annual cohorts implies a constant exposure and presence of active foci transmission preceding the survey. [ABSTRACT FROM AUTHOR]

Background: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses. Methodology/Principal Findings: Parasitaemic individuals (n = 116) were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16), developed circulating gametocytes by day 7 (n = 69) or between day 7 and 14 (n = 10) after treatment or did not develop gametocytes (n = 21). Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals). Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348) and 15.2% (53/348) of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-119 (48.1%; 137/285) and AMA-1 (52.4%; 129/246)(p<0.001). The prevalence of anti-Pfs230 (p = 0.026) and anti-Pfs48/45 antibodies (p = 0.017) increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01). Conclusions/Significance: In a longitudinal study, anti-Pfs230 and Pf48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses. [ABSTRACT FROM AUTHOR]

Background: Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria. Methods: Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures. Results: The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI). Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144%) in uninfected donors. All donors showed a response towards IL-1β production, drawing special attention for its possible protective role in early innate immune responses to malaria. Conclusions: In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare. Methods: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models. Results: Of 788 participants, 513 were aged ≤17 years. H. pylori seropositivity increased from 76% at 0–4 years to 99% by ≥18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2–31.4 for 10–17 vs. 0–4 years), higher birth-order (11.1; 3.6–34.1 for ≥3rd vs. 1st born), and having a seropositive next-older sibling (2.7; 0.9–8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7–5.6), consistent with a Th2- dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3–4.4). Conclusion: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa. [ABSTRACT FROM AUTHOR]