The trade-off between accuracy and accessibility of syphilis screening assays.

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

The impact of antiretroviral therapy on adult mortality in rural Tanzania.

OBJECTIVE: To describe the impact of antiretroviral therapy (ART) on mortality rates among adults participating in an HIV community cohort study in north-west Tanzania. METHODS: Serological and demographic surveillance rounds have been undertaken in a population of approximately 30,000 people since 1994. Free HIV care including ART has been available since 2005. Event history analysis was used to compare mortality rates among HIV-negative and HIV-positive adults in the 5-year period before and after the introduction of ART. Crude and adjusted hazard ratios were calculated using exponential regression models. Interaction between time period and HIV status was assessed to investigate whether there was a non-linear relationship between these two variables. RESULTS: Male and female mortality patterns varied over the pre- and post-ART period. In women, the crude death rate fell for both HIV negatives and HIV positives hazard rate ratio (HRR = 0.71; 95%CI 0.51-0.99 and HRR = 0.68; 95%CI: 0.46-0.99, respectively). For men, the mortality among the HIV negatives increased (HRR = 1.47; 95%CI: 1.06-2.03) while the decline in mortality among the HIV positives (HRR = 0.77; 95%CI 0.52-1.13) was not statistically significant. The largest decrease in HIV-positive mortality over the two periods was among the 30- to 44-year-old age group for women and among the 45- to 59-year-old age group for men. CONCLUSION: There has been a modest effect on mortality in the study population following the introduction of free ART 5 years ago. Improving access to treatment and placing greater focus on retaining individuals on treatment are essential if the full potential of treatment for reducing HIV-related mortality is to be realised

Trends in the Uptake of Voluntary Counselling and Testing for HIV in Rural Tanzania in the Context of the Scale up of Antiretroviral Therapy.

To describe trends in voluntary counselling and testing (VCT) use and to assess whether high-risk and infected individuals are receiving counselling and learning their HIV status in rural Tanzania. During two rounds of linked serological surveys (2003-2004 and 2006-2007) with anonymous HIV testing among adults, VCT was offered to all participants. The crude and adjusted odds ratios for completing VCT in each survey were calculated to compare uptake by demographic, behavioural and clinical characteristics, stratified by sex. Repeat testing patterns were also investigated. The proportion of participants completing VCT increased from 10% in 2003-2004 to 17% in 2006-2007, and among HIV-infected persons from 14% to 25%. A higher proportion of men than women completed VCT in both rounds, but the difference declined over time. Socio-demographic and behavioural factors associated with VCT completion were similar across rounds, including higher adjusted odds of VCT with increasing numbers of sexual partners in the past 12 months. The proportion having ever-completed VCT reached 26% among 2006-2007 attendees, with repeat testing rates highest among those aged 35-44 years. Among 3923 participants attending both rounds, VCT completion in 2006-2007 was 17% among 3702 who were HIV negative in both rounds, 19% among 124 who were HIV infected in both rounds and 22% among 96 who seroconverted between rounds. VCT services are attracting HIV-infected and high-risk individuals. However, 2 years after the introduction of antiretroviral therapy, the overall uptake remains low. Intensive mobilisation efforts are needed to achieve regular and universal VCT use

The implementation of an external quality assurance method for point- of- care tests for HIV and syphilis in Tanzania.

BACKGROUND: External quality assurance (EQA) programmes, which are routinely used in laboratories, have not been widely implemented for point-of- care tests (POCTs). A study was performed in ten health centres in Tanzania, to implement the use of dried blood spots (DBS) as an EQA method for HIV and syphilis (POCTs). METHOD: DBS samples were collected for retesting at a reference laboratory and the results compared to the POCT results obtained at the clinic. In total, 2341 DBS samples were collected from 10 rural health facilities over a period of nine months, of which 92.5% were correctly collected and spotted. RESULTS: The EQA method was easily implemented by healthcare workers under routine conditions in Northern Tanzania. For HIV, 967 out of 972 samples (99.5%) were concordant between DBS and POCT results. For syphilis, the sensitivity of syphilis tests varied between clinics with a median of 96% (25th and 75th quartile; 95-98%). The specificity of syphilis POCT was consistent compared to laboratory based test using DBS, with a median of 96% (25th and 75th quartiles; 95-98%). CONCLUSION: Overall, the quality of testing varied at clinics and EQA results can be used to identify clinics where healthcare workers require remedial training, suggesting the necessity for stringent quality assurance programmes for POC testing. As Tanzania embarks on scaling up HIV and syphilis testing, DBS can be a useful and robust tool to monitor the quality of testing performed by healthcare workers and trigger corrective action to ensure accuracy of test results

Refining Diagnosis of Schistosoma haematobium Infections: Antigen and Antibody Detection in Urine

Background: Traditional microscopic examination of urine or stool for schistosome eggs lacks sensitivity compared to measurement of schistosome worm-derived circulating antigens in serum or urine. The ease and non-invasiveness of urine collection makes urine an ideal sample for schistosome antigen detection. In this study several user-friendly, lateral-flow (LF) based urine assays were evaluated against a composite reference that defined infection as detection of either eggs in urine or anodic antigen in serum.Method: In a Tanzanian population with a S. haematobium prevalence of 40–50% (S. mansoni prevalence <2%), clinical samples from 44 women aged 18 to 35 years were analyzed for Schistosoma infection. Urine and stool samples were examined microscopically for eggs, and serum samples were analyzed for the presence of the anodic antigen. Urines were further subjected to a set of LF assays detecting (circulating) anodic (CAA) and cathodic antigen (CCA) as well as antibodies against soluble egg antigens (SEA) and crude cercarial antigen preparation (SCAP).Results: The urine LF anodic antigen assay utilizing luminescent upconverting reporter particles (UCP) confirmed its increased sensitivity when performed with larger sample volume. Qualitatively, the anodic antigen assay performed on 250 μL urine matched the performance of the standard anodic antigen assay performed on 20 μL serum. However, the ratio of anodic antigen levels in urine vs. serum of individual patients varied with absolute levels always higher in serum. The 10 μL urine UCP-LF cathodic antigen assay correlated with the commercially available urine POC-CCA (40 μL) test, while conferring better sensitivity with a quantitative result. Urinary antibodies against SEA and SCAP overlap and correlate with the presence of urinary egg and serum anodic antigen levels.Conclusions: The UCP-LF anodic antigen assay using 250 μL of urine is an expedient user-friendly assay and a suitable non-invasive alternative to serum-based antigen testing and urinary egg detection. Individual biological differences in the clearance process of the circulating antigens are thought to explain the observed high variation in the type and level of antigen (anodic or cathodic) measured in urine or serum. Simultaneous detection of anodic and cathodic antigen may be considered to further increase accuracy

HIV-seroconversion among HIV-1 serodiscordant married couples in Tanzania: a cohort study.

BACKGROUND: Heterosexual transmission is the main driver of the HIV epidemic in Tanzania. Only one estimate of the incidence rate of intra-marital HIV seroconversion in Tanzania has been reported and was derived from data collected between 1991 and 1995. Moreover, little is known about the specific risk factors for intra-marital seroconversion in Tanzania. Improved evidence around factors that increase the risk of HIV transmission to a serodiscordant spouse is needed to develop and improve evidence-based interventions. We sought to investigate the rate of intra-marital HIV seroconversion among HIV sero-discordant couples in Tanzania as well as its associated risk factors. METHODS: We identified all HIV positive individuals in the TAZAMA HIV-serosurvey cohort and followed up their serodiscordant spouse from 2006 to 2016. The rate of seroconversion was analyzed by survival analysis using non-parametric regressions with exponential distribution. RESULTS: We found 105 serodiscordant couples, 14 of which had a seroconverting spouse. The overall HIV-1 incidence rate among spouses of people with HIV-1 infection was 38.0 per 1000 person/years [22.5-64.1]. Notably, the HIV-1 incidence rate among HIV-1 seronegative male spouses was 6.7[0.9-47.5] per 1000 person/years, compared to 59.3 [34.4-102.1] per 1000 person/years among female spouses. Sex of the serodiscordant spouse was the only significant variable, even after adjusting for other variables (Hazard rate = 8.86[1.16-67.70], p = 0.036). CONCLUSIONS: Our study suggests that rates of HIV-1 seroconversion of sero-discordant partners are much higher within marriage than in the general population in Tanzania. The major risk factor for HIV-1 seroconversion is sex of the serodiscordant spouse, with female spouses being at very high risk of acquiring HIV infection. This suggests that future programs that target serodiscordant couples could be a novel and effective means of preventing HIV-1 transmission in Tanzania

Hand hygiene intervention to optimise soil-transmitted helminth infection control among primary school children: the Mikono Safi cluster randomised controlled trial in northwestern Tanzania.

BACKGROUND: Soil-transmitted helminth (STH) infections are highly prevalent in resource-limited countries. We assessed the effect of a combination intervention aiming to enhance handwashing with soap on STH reinfection following mass drug administration among primary school children in Kagera region, Northwestern Tanzania. METHODS: We conducted a cluster randomised trial in sixteen primary schools with known high STH prevalence. Schools were randomly assigned in a 1:1 ratio to either receive the intervention or continue with routine health education. The intervention included teacher-led classroom teaching, parental engagement sessions, environmental modifications and improved handwashing stations. The evaluation involved two cross-sectional surveys in a representative sample of students, with the end-line survey conducted 12 months after the baseline survey. The primary outcome was the combined prevalence of Ascaris lumbricoides and Trichuris trichiura infections at the end-line survey. Secondary outcomes included reported handwashing behaviour, the prevalence and intensity of individual STHs, and hand contamination with STH ova and coliform bacteria. End-line STH prevalence and intensity were adjusted for baseline differences of potential confounders. RESULTS: At the end-line survey, 3081 school children (1566 from intervention schools and 1515 from control schools) provided interview data and stool specimens. More school children in the intervention group reported the use of water and soap during handwashing compared to school children in the control group (58% vs. 35%; aOR=1.76, 95%CI 1.28-2.43, p=0.001). The combined prevalence of A. lumbricoides and T. trichiura infections was 39% in both trial arms (aOR = 1.19; 95%CI 0.74-1.91). The prevalence of A. lumbricoides was 15% in the intervention and 17% in the control arm (aOR =1.24, 95%CI 0.59-2.59) and that of T. trichiura was 31% in both arms (aOR=1.17, 95%CI 0.73-1.88). No significant differences were found for STH infection intensity in both the main study and the hand contamination sub-study. CONCLUSIONS: The intervention was effective in increasing reported handwashing behaviour at school, but failed to show a similar effect in the home. The intervention had no effect on STH infection, possibly due to infection in the home environment, other transmission routes such as contaminated water or food or limited changes in school children's handwashing behaviour. TRIAL REGISTRATION: The trial was registered on June 21, 2017, by the International Standard Randomised Controlled Trial Number ( ISRCTN45013173)

HIV-1 Viral Loads Are Not Elevated in Individuals Co-infected With Schistosoma spp. After Adjustment for Duration of HIV-1 Infection

Studies of the role of Schistosoma co-infections on plasma HIV-1 RNA (HIV-1 viral load) have yielded incongruent results. The role of duration of HIV-1 infection on the link between Schistosoma and HIV-1 viral load has not been previously investigated. We aimed to assess the impact of HIV-1/Schistosoma co-infections on viral load in Antiretroviral Treatment (ART)-naïve HIV-1 infected people taking into account the duration of HIV-1 infection. We describe 79 HIV-infected outpatients greater than 18 years of age who had never used ART in Mwanza, Tanzania. Schistosomiasis testing was done by urine and stool microscopy and by serum Schistosoma circulating anodic antigen (CAA) testing. Schistosoma positivity was defined as having either test positive. We conducted univariable and multivariable linear regressions to assess the relationship between Schistosoma infection and the log10 of viral load. Duration of HIV infection was calculated using the first measured CD4+ T-cell (CD4) count as a function of normal CD4 count decay per calendar year in drug naïve individuals. An active Schistosoma infection was demonstrated in 46.8% of the patients. The median log10 viral load was 4.5[3.4–4.9] log10 copies/mL in Schistosoma uninfected patients and 4.3[3.7–4.6] log10 copies/mL in Schistosoma infected patients. Schistosoma co-infection was negatively associated with the log10 of viral load after adjustment for Schistosoma intensity as measured by CAA, CD4 counts at time of testing, and duration of HIV-1 infection (β = −0.7[−1.3;−0.1], p = 0.022). Schistosoma co-infection was not associated with viral load in univariable analysis. There was also no interaction between Schistosoma positivity and duration of HIV-1 infection. Our study is the first, to our knowledge, to report adjustment for duration of HIV-1 infection when analyzing the relationship between HIV-1 viral load and Schistosoma spp. We found that time infected with HIV-1 has a major effect on the relationship between HIV-1 viral load and Schistosoma infection and may be a critical explanatory factor in the disparate findings of studies on HIV-1 viral load and schistosomiasis. The log10 viral load difference found indicates that Schistosoma co-infection does not make HIV progression worse, and could possibly lead to slower HIV disease progression

Reproductive behaviour and HIV status of antenatal clients in northern Tanzania: opportunities for family planning and preventing mother-to-child transmission integration.

OBJECTIVES: To examine reproductive and contraceptive history and intentions by HIV status among women at antenatal clinics to help inform initiatives to integrate family planning into antenatal/preventing mother-to-child transmission services in Mwanza region, Tanzania. DESIGN: A questionnaire survey was carried out in antenatal clinics in Mwanza region, Tanzania in 2007-2008. METHODS: : We interviewed 5284 pregnant women attending 15 antenatal clinics offering HIV testing in Mwanza City and Magu district, northern Tanzania. The questionnaires asked about reproductive and contraceptive history and intentions, and sexual behaviour. Subject to participants' consent, we collected blood to determine HIV status and linked these results to the questionnaire data through individual numbers. RESULTS: HIV prevalence was 8.9% overall, and family planning ever use was 26%. HIV-positive and HIV-negative women differed with respect to age, parity, length of last birth interval, child survival, childbearing intentions and intention to breastfeed. HIV-positive women were more likely to have used family planning, particularly hormonal methods. Patterns of family planning use and unmet need for contraception yielded useful information for the design of family planning counselling services at antenatal clinics. CONCLUSION: Our survey findings point to numerous potential benefits of offering family planning counselling as a part of antenatal services, particularly in clinics offering HIV testing. The differences in reproductive history and intentions between HIV-positive and HIV-negative women highlight the necessity of tailoring family planning counselling to their specific needs

Uptake of HIV voluntary counselling and testing services in rural Tanzania: implications for effective HIV prevention and equitable access to treatment.

OBJECTIVE: To describe the associations between socio-demographic, behavioural and clinical characteristics and the use of HIV voluntary counselling and testing (VCT) services among residents in a rural ward in Tanzania. METHODS: Eight thousand nine hundred and seventy participants from a community-based cohort were interviewed, provided blood for research HIV testing, and were offered VCT. Univariate and multivariate logistic regression was used to identify socio-demographic, clinical and behavioural factors associated with VCT use. RESULTS: Although 31% (1246/3980) of men and 24% (1195/4990) of women expressed an interest in the service, only 12% of men and 7% of women subsequently completed VCT. Socio-demographic factors, such as marital status, area of residence, religion and ethnicity influenced VCT completion among males and females in different ways, while self-perceived risk of HIV, prior knowledge of VCT, and sex with a high-risk partner emerged as important predictors of VCT completion among both sexes. Among males only, those infected with HIV for 5 years or less tended to self-select for VCT compared to HIV-negatives (adjusted odds ratio = 1.43; 95% CI: 0.99-2.14). This contributed to a higher proportion of HIV-positive males knowing their status compared to HIV-positive females. CONCLUSIONS: In this setting, a disproportionate number of HIV-positive women are failing to learn their status, which has implications for equitable access to onward referral for care and treatment services. Evidence that some high-risk behaviours may prompt VCT use is encouraging, although further interventions are required to improve knowledge about HIV risk and the benefits of VCT. Targeted interventions are also needed to promote VCT uptake among married women and rural residents