Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

High prevalence of ST-elevation, early repolarization, and left ventricular hypertrophy during the eligibility assessment for an HIV vaccine trial in young, healthy Tanzanians

BACKGROUND: Vaccinia based immunizations have caused myo/pericarditis and vaccine study volunteers are monitored by ECG. We report ECG outcome obtained during the screening period for an HIV vaccine trial. METHODS: ECG was performed in healthy Tanzanian volunteers. ECG abnormalities and findings interfering with the interpretation of myo/pericarditis were subject to study ineligibility. We determined the prevalence of left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon (SL) or the Cornell index, ST-elevations and early repolarization (ERP) in association with gender, age, BMI and body height by regression analysis adjusted for gender and age. RESULTS: In 257 volunteers (median age 23 years, 63% males) overall positivity for LVH defined by SL or Cornell criteria was seen in 20.6% and 3.5%, ST-elevations ≥ 0.1 mV or ≥ 0.2 mV in 77.8% and 38.1%, and ERP in 23.4%. Positive SL criteria were associated with male gender (PR 7.84, p < 0.001) and lower age (PR 0.70, p = 0.002), and associated with increased body height and lower BMI in univariate analysis. Positive Cornell criteria were only associated with lower age (PR 0.44, p = 0.010). ST-elevations ≥ 0.2 mV were associated with male gender (PR 8.05, p < 0.001) and lower age (PR 0.81, p = 0.003), and ERP with male gender (PR 2.86, p < 0.001). Vaccine study ineligibility due to ECG findings was concluded in 22.1% of the screening population. CONCLUSIONS: High prevalence of LVH according to SL in association with ST-elevation and ERP is especially found in young and male Africans. ECG variations need to be considered for eligibility criteria in studies investigating potential cardiotoxic agents in Africa

Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA prime - Modified Vaccinia Ankara (MVA) boost HIV-1 vaccine regimen

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced IFN-γ(+) Gag-specific T cell responses were dominated by CD4(+) T cells (compared to CD8(+) T cells, p<0.001) that co-expressed IL-2 (66.4%) and/or TNFα (63.7%). A median of 3 antigenic regions were targeted with a higher median response magnitude to Gagp24 regions - more conserved between prime and boost - as compared to regions within Gagp15 (not primed) and Gagp17 (less conserved, both p<0.0001). Four regions within Gagp24 were each targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA and DNA Gag encoded immunogens (p=0.04, r(2)=0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T cell response that was dominated by polyfunctional CD4(+) T cells and that targeted multiple antigenic regions within the conserved Gagp24 Protein.IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved; either by improved cross-recogniton of multiple variants for a given antigenic region or rather through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses

High Seroprevalence of Rift Valley Fever and Evidence for Endemic Circulation in Mbeya Region, Tanzania, in a Cross-Sectional Study

We describe a high seropositivity rate for Rift Valley fever virus, in up to 29.3% of tested individuals from the shore of Lake Malawi in southwestern Tanzania, and much lower rates from areas distant to the lake. Rift Valley fever disease or outbreaks have not been observed there in the past, which suggests that the virus is circulating under locally favorable conditions and is either a non-pathogenic strain, or that occasional occurrence of disease is missed. We were able to identify a low socio-economic status and cattle ownership as possible socio-economic risk factors for an individual to be seropositive. Environmental risk factors associated with seropositivity include dense vegetation, and ambient land surface temperatures which may be important for breeding success of the mosquitoes which transmit Rift Valley fever, and for efficient multiplication of the virus in the mosquito. Low elevation of the home, and proximity to Lake Malawi probably lead to abundant surface water collections, which serve as breeding places for mosquitoes. These findings will inform patient care in the areas close to Lake Malawi, and may help to design models which predict low-level virus circulation