Globally, Cryptosporidium spp. is the most common diarrhea‐causing protozoan infection among children at health facilities. Infection may be asymptomatic or may manifest as severe, chronic diarrhea especially in malnourished or HIV‐positive individuals. Long‐term physical and cognitive impairment has been associated with infection. The objective of this study was to determine the prevalence of Cryptosporidium spp . infection among mothers and children from birth to 6 months, and to understand how breastfeeding practices relate to infection. This prospective cohort of 100 mother/infant pairs was conducted at a peri‐urban health clinic in northwestern Tanzania and 38% of infants were HIV‐exposed. Feeding/health questionnaires, anthropometrics and stool samples were obtained at Month 1, 2, 3 after birth. Approximately 1/3 of mothers had evidence of Cryptosporidium spp. at each visit; while infant infections did not appear until Month 3 when 11% were positive. These results indicate that mothers and infants are living in a Cryptosporidium spp. environment; however, infants remain uninfected until at least 3 months. Infection timing may be due to maternal immunological protection provided in utero, in breast milk and/or because exclusive breastfeeding eliminates the opportunity for exposure to contaminated food or water. Our ongoing research is focused on identifying mechanisms of protection and risk. Grant Funding Source : Cornell University Unrestricted Grant
Objectives Cervical cancer is the leading cause of cancer-related mortality among women in sub-Saharan Africa (SSA). Data on human papillomavirus (HPV) epidemiology in adolescent girls in SSA are essential to inform HPV vaccine policy recommendations for cervical cancer prevention. We assessed the burden of HPV infection, and risk factors for infection, among adolescent girls around the time of sexual debut. Methods Cross-sectional study of secondary school girls aged 17–18 years in Tanzania. Consenting participants provided samples for HPV and STI testing. Vaginal swabs were tested for 37 HPV genotypes by Roche Linear Array. Logistic regression was used to identify factors associated with HPV infection. Y chromosome was tested as a marker of recent condomless sex. Results 163/385 girls (42.3%) reported previous penetrative sex. HPV was detected in 125/385 (32.5%) girls, including 84/163 (51.5%) girls reporting previous sex and 41/222 (18.5%) reporting no previous sex. High-risk (HR) genotypes were detected in 70/125 (56.0%) girls with HPV infection. The most common HR genotype was HPV-16 (15/385; 3.9%). The prevalence of other HR HPV vaccine genotypes was between 0.8% and 3.1%. Among 186 girls who reported no previous sex, were negative for Y chromosome, and had no STI, 32 (17%) had detectable HPV. Lactobacillus sp and bacterial vaginosis-associated bacteria were negatively and positively associated, respectively, with HPV. Conclusions HPV prevalence among adolescent girls around the time of sexual debut was high. However, prevalence of most vaccine genotypes was low, indicating that extending the age range of HPV vaccination in this region may be cost-effective.
Background Infection causes immune activation and inflammatory cytokines may be mediators of intrauterine growth restriction (IUGR). While infection and IUGR are common in developing regions, the intrauterine cytokine environment and its impact on birth size is undefined. Understanding the fetal environment mediated by multiple cytokines may inform interventions targeting birth anthropometry. Objective To investigate the relationship between umbilical cord cytokines and birth size. Methods Umbilical cord cytokines (IFN‐γ, IL‐1β, IL‐2, IL‐6, TNF‐α, IL‐12p70, IL‐10, IL‐13) were multiplexed from 50 singleton deliveries of women residing in rural Tanzania (38% HIV‐positive). Birth weight and length were assessed using linear regression models adjusted for maternal age, nutritional status, HIV, and infant gender.
Results Cord IFN‐γ, IL‐1β, TNF‐α, IL‐12p70, and IL‐10 were each associated with reduced birth weight (grams; ‐532, P<0.01; ‐372, P=0.04; ‐315, P=0.03; ‐721, P<0.01; ‐278, P=0.04; respectively) and IFN‐γ, TNF‐α, and IL‐12p70 with reduced length. image image Cord cytokines were not associated with gestational age at delivery and did not differ based on maternal HIV status.
Conclusions Elevated cord blood cytokines, which suggest intrauterine immune activation and inflammation, were associated with clinically important reductions in birth weight and length. Understanding these relationships may be key to optimizing fetal growth outcomes in this setting.
Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact. Methods. In this phase IIIb, double-blind, randomized, placebo-controlled, multicenter trial (NCT00481767), healthy African girls and young women seronegative for human immunodeficiency virus (HIV) were stratified by age (10–14 or 15–25 years) and randomized (2:1) to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 450) or placebo (n = 226) at 0, 1, and 6 months. The primary objective was to evaluate HPV-16/18 antibody responses at month 7. Seropositivity rates and corresponding geometric mean titers (GMTs) were measured by enzyme-linked immunosorbent assay. Results. In the according-to-protocol analysis at month 7, 100% of initially seronegative participants in the vaccine group were seropositive for both anti–HPV-16 and anti–HPV-18 antibodies (n = 130 and n = 128 for 10–14-year-olds, respectively; n = 190 and n = 212 for 15–25-year-olds). GMTs for HPV-16 and HPV-18 were higher in 10–14-year-olds (18 423 [95% confidence interval, 16 185–20 970] and 6487 [5590–7529] enzyme-linked immunosorbent assay units (EU)/mL, respectively) than in 15–25-year-olds (10 683 [9567–11 930] and 3743 [3400–4120] EU/mL, respectively). Seropositivity was maintained at month 12. No participant withdrew owing to adverse events. No vaccine-related serious adverse events were reported. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic and had a clinically acceptable safety profile when administered to healthy HIV-seronegative African girls and young women.
The availability of rapid and sensitive methods to diagnose syphilis facilitates screening of pregnant women, which is one of the most cost-effective health interventions available. We have evaluated two screening methods in Tanzania: an enzyme immunoassay (EIA), and a point-of-care test (POCT). We evaluated the performance of each test against the Treponema pallidum particle agglutination assay (TPPA) as the reference method, and the accessibility of testing in a rural district of Tanzania. The POCT was performed in the clinic on whole blood, while the other assays were performed on plasma in the laboratory. Samples were also tested by the rapid plasma Reagin (RPR) test. With TPPA as reference assay, the sensitivity and specificity of EIA were 95.3% and 97.8%, and of the POCT were 59.6% and 99.4% respectively. The sensitivity of the POCT and EIA for active syphilis cases (TPPA positive and RPR titer ≥ 1/8) were 82% and 100% respectively. Only 15% of antenatal clinic attenders in this district visited a health facility with a laboratory capable of performing the EIA. Although it is less sensitive than EIA, its greater accessibility, and the fact that treatment can be given on the same day, means that the use of POCT would result in a higher proportion of women with syphilis receiving treatment than with the EIA in this district of Tanzania.
To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors.Women aged 18-44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models.We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82).HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population.
Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in young female subjects recruited for a safety and immunogenicity trial of the bivalent HPV-16/18 vaccine in Tanzania. Methods Healthy HIV negative female subjects aged 10–25 years were enrolled and randomised (2:1) to receive HPV-16/18 vaccine or placebo (Al(OH) 3 control). At enrolment, if sexually active, genital specimens were collected for HPV DNA, other reproductive tract infections and cervical cytology. Subjects were followed to 12 months when HPV testing was repeated. Results In total 334 participants were enrolled; 221 and 113 in vaccine and control arms, respectively. At enrolment, 74% of 142 sexually active subjects had HPV infection of whom 69% had >1 genotype. Prevalent infections were HPV-45 (16%), HPV-53 (14%), HPV-16 (13%) and HPV-58 (13%). Only age was associated with prevalent HPV infection at enrolment. Among 23 girls who reported age at first sex as 1 year younger than their current age, 15 (65.2%) had HPV infection. Of 187 genotype-specific infections at enrolment, 51 (27%) were present at 12 months. Overall, 67% of 97 sexually active participants with results at enrolment and 12 months had a new HPV genotype at follow-up. Among HPV uninfected female subjects at enrolment, the incidence of any HPV infection was 76 per 100 person-years. Conclusions Among young women in Tanzania, HPV is highly prevalent and acquired soon after sexual debut. Early HPV vaccination is highly recommended in this population.
Background Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness. Sequence-based analysis of the multiple strains typically present in endemic communities may be informative for epidemiology, transmission, response to treatment, and understanding the host response. Methods Conjunctival and nasal samples from a Gambian community were evaluated before and 2 months after mass azithromycin treatment. Samples were tested for Ct by Amplicor, with infection load determined by quantitative PCR (qPCR). ompA sequences were determined and their diversity analysed using frequency-based tests of neutrality. Results Ninety-five of 1,319 (7.2%) individuals from 14 villages were infected with Ct at baseline. Two genovars (A and B) and 10 distinct ompA genotypes were detected. Two genovar A variants (A1 and A2) accounted for most infections. There was an excess of rare ompA mutations, not sustained in the population. Post-treatment, 76 (5.7%) individuals had Ct infection with only three ompA genotypes present. In 12 of 14 villages, infection had cleared, while in two it increased, probably due to mass migration. Infection qPCR loads associated with infection were significantly greater for A1 than for A2. Seven individuals had concurrent ocular and nasal infection, with divergent genotypes in five. Conclusions The number of strains was substantially reduced after mass treatment. One common strain was associated with higher infection loads. Discordant genotypes in concurrent infection may indicate distinct infections at ocular and nasal sites. Population genetic analysis suggests the fleeting appearance of rare multiple ompA variants represents purifying selection rather than escape variants from immune pressure. Genotyping systems accessing extra-ompA variation may be more informative.
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