Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 ...pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.
In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46.
129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups.
A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.
World Health Organization International Clinical Trials Registry Platform PACTR2010050002122368.
Stroke contributes to a significant proportion of deaths and disability worldwide, with a high fatality rate within 30 days following a first ever stroke. We describe the outcomes within one year ...among patients who succumbed a first ever stroke and survived the first 30 days.
Participants were patients who survived after 30 days from succumbing a first ever stroke admitted at the Muhimbili University of Health and Allied Sciences Academic Medical Center. Stroke survivors or their next of kin were contacted at one year after succumbing a first stroke to determine the outcomes. We assessed participants' vital status and level of disability using the modified Rankin scale. Assessment on utilization of stroke secondary preventive measures among survivors was done by an interviewer-based questionnaire that assessed the number of times participants attended follow up clinics, medication refill and adherence. Participants were examined for waist-hip ratio, body mass index and blood pressure. Cholesterol levels were assessed at one year post first stroke for survivors. Outcomes were summarized as proportions, survival at one year was estimated by using the Kaplan Meier analysis and Cox regression analysis was performed to determine for predictors of mortality.
We recruited 130 first stroke survivors. Mortality within one year was 53/130 (40.8%) and disability rate measured by Modified Rankin Scale with scores of 3-5 was 29/77 (37.7%) among survivors. Factors associated with mortality were residual disability HR = 8.60, {95% CI (1.16-63.96)}, severe stroke, HR = 2.67 {95% CI (1.44-4.95)} and residing in Dar-es-Salaam HR = 2.15 {95% (CI 1.06-4.36)}. Non-adherence rates to antihypertensives, antiplatelets and statins was 11/73 (15.1%), 9/23 (39.1%) and 18/22 (81.8%) respectively. Attendance rates of follow-up clinics among all survivors and physiotherapy among survivors with disability are 45/77 (58.4%) and 16/29 (55.2%) respectively.
The mortality and disability rates within a year following a first ever stroke among 30 days stroke survivors is high. Secondary stroke preventive measures should be enhanced to mitigate stroke adverse outcomes. Community outreach programs could be useful interventions in preventing the adverse outcomes of stroke.
A bi-directional interaction between diabetes mellitus and tuberculosis is well established and has been likened to that between HIV and TB. Whereas HIV screening is standard of care test in sub ...Saharan Africa TB programs, the same is not true for diabetes mellitus (DM). Sub Saharan Africa, a region with high TB infection rates, is going through an epidemiological transition with rapidly rising prevalence of diabetes. We aimed at characterizing TB patients with DM in order to identify factors associated with TB-DM dual disease among patients attending TB clinics in Dar es Salaam.
A cross-sectional study was conducted between September 2016 and January 2017 among patients attending TB clinics in Dar es Salaam. We collected socio-demographic characteristics, anthropometric measurements and screened for diabetes by measuring fasting blood glucose that was followed by a 2 h postprandial glucose for participants with impaired fasting blood glucose. We examined for socio-demographic and clinical factors associated with diabetes using logistic regression analysis.
Of the 660 enrolled participants with TB, 25 (3.8%) were on treatment for diabetes while 39 (6.1%) and 147 (23%) of the remaining 635 participants were ultimately diagnosed with DM and impaired fasting blood glucose respectively. The overall prevalence of DM was 9.7% (64/660). Independent risk factors for diabetes included: age > 44 years {OR 4.52, 95% CI: 1.28-15.89}; family history of diabetes {OR 3.42, 95% CI 1.88-6.21}. HIV sero-positive TB patients were less likely to have DM compared to those who were HIV sero-negative {OR 0.35, 95% CI 0.17-0.73}.
Screening for diabetes should be advocated for TB patients aged above 44 years and/or with a family history of diabetes. HIV sero-negative TB patients were more likely to have DM compared to those who were HIV sero-positive. Further studies are needed to confirm this observation and the underlying factors.
T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, ...borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (greater than or equal to2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.
Stroke burden in young adults is growing associated with unique risk factors and devastating outcomes. We aimed to investigate the magnitude, risk factors and outcomes of first ever stroke in young ...adults ≤45 years compared to older adults > 45 years.
All patients with a World Health Organization clinical definition of stroke at a tertiary hospital in Tanzania were enrolled. The National Institute of Health Stroke Scale and Modified Rankin Scale were used to assess admission stroke severity and outcomes respectively. Kaplan-Meier analysis was used to describe survival and Cox-proportional hazards model was used to examine predictors of fatality.
We enrolled 369 first ever stroke participants over 8 months. First strokes accounted for one quarter of the medical admissions in both younger and older groups, 123/484 {(25.4%) 95% CI 21.5-29.3%} and 246/919 {(26.8%) 95% CI 23.9-29.6%} respectively. Hemorrhagic stroke occurred in 47 (42.3%) vs 62 (27.2%) for the young and old respectively p = 0.005. Factors associated with stroke in the young were: a new diagnosis of hypertension in 33 (26.8%) vs 23 (9.3%) p < 0.001, HIV infection 12 (9.8%) vs 7 (2.8%) p = 0.005, use of hormonal contraception in females 33 (48.5%) vs 13 (9.4%) p < 0.001, elevated serum low density lipoproteins 28 (27.7%) vs 29 (16.4%) p = 0.024, hypercholesteremia 34 (31.2%) vs 40 (20.2%), p = 0.031, sickle cell disease 11 (9.7%) vs 9 (4.2%) p = 0.047 and thrombocytosis 12 (16.9%) vs 8 (5.6%) p = 0.007. The overall 30-day fatality rate was 215 (61.3%); 57 (49.1%) vs 158 (67.2%) in the young and old respectively. Independent predictors of fatality were: severe stroke {HR 10.35 (95% CI: 1.397-76.613)}, leukocytosis {HR 2.23 (95% CI: 1.448-3.419)} and fever {HR 1.79 (95% CI: 1.150-2.776)}.
There is a high burden of stroke in young adults that is coupled with a high 30-day fatality rate. Screening and management of hypertension is crucial in the prevention of stroke. More research is needed to identify factors which cause death, allowing the development of sustainable interventions to reduce early post stroke fatality in this group.
There has been an increase in the number of individuals aged ≥60 years in Tanzania and in sub Saharan Africa in general due to improved survival. However, data is scarce on the disease burden and ...outcomes following admission in this population. We herein describe the pattern of diagnoses, outcomes and factors associated with the outcomes among elderly patients admitted at Muhimbili National Hospital (MNH) and Jakaya Kikwete Cardiac Institute (JKCI) medical wards.
From October to December 2017, we consecutively enrolled patients aged ≥60 years (elderly) admitted to the MNH and JKCI medical wards. The ICD 10 was used to code for disease diagnosis at discharge or death. The Modified Barthel index was used to assess for functional activity on admission and at discharge.
We enrolled 336 (30.1%) elderly participants out of 1301 medical admissions. The mean age ± SD was 70.6 ± 8.9 years; 169 (50%) were female and the average number of diagnoses was 2 per participant. The most common diagnoses were: hypertension 151 (44.9%), stroke 106 (31.5%), heart failure 62 (18.5%), pneumonia 60 (17.9%), diabetes mellitus 58 (17.3%) and chronic kidney disease 55 (16.4%). The median duration of hospital stay was 5 (IQR 3-10) days and in-hospital mortality was 86 (25.6%), 56 (65%) deaths were due to non-communicable diseases and 48 (55.8%) deaths occurred within 72 hours of hospitalization. A modified Barthel score ≤20 on admission was associated with an OR 15.43 (95% CI: 7.5-31.7, p<0.001) for death.
Elderly patients constituted a significant proportion of medical admissions at MNH and JKCI with high in-hospital mortality. A modified Barthel index score ≤20 during admission is associated with mortality and can be used to identify patients requiring special attention.
ObjectivesWe aimed to determine the prevalence, associated factors and describe the chest radiographic findings for active pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM) ...attending a diabetic clinic in Tanzania.DesignCross-sectional study.SettingA diabetic clinic at Temeke Regional Referral Hospital in Dar es salaam, Tanzania.ParticipantsPatients with diabetes.Main outcome measuresThe prevalence and factors associated with active TB in patients with DM.ResultsAmong 623 patients with DM screened, 11 (1.8%); 95% CI 0.9 to 3.1, had active TB of which 6 (54.5%) were GeneXpert positive and 5 (45.5%) were diagnosed based on clinical symptoms and suggestive chest radiographs. The risk of active TB was lower in patients aged 45–64 years compared with age below 45 years (adjusted prevalence ratio (aPR) 0.39, 95% CI (0.11 to 0.42), p=0.001) and in patients with normal chest examination findings compared with patients with crackles or bronchial breathing sounds (aPR 0.02, 95% CI (0.01 to 0.15), p<0.01). The predominant chest radiographic findings were opacification 100% mainly in the upper and mid-lung zones.ConclusionDiabetics should be screened for pulmonary TB, particularly among individuals aged 45 years and below with crackles or bronchial breathing on auscultation of the chest. High index of suspicion could help in the early detection and control of TB.
ObjectivesTo explore the potential use of body mass index (BMI), proteinuria and total lymphocyte count changes in predicting immunological and virological response in individuals with HIV initiated ...on antiretroviral treatment (ART).DesignProspective cohort study.SettingThree urban HIV care and treatment centres in Dar es Salaam.ParticipantsIndividuals with HIV initiating ART.Outcome measuresHIV viral load ≥1000 copies/mL (viral non-suppression) at 6 months after ART initiation.ResultsOf 215 (out of 220 enrolled) participants who returned for evaluation at 6 months, 147 (66.8%) were women. At 6 months of follow-up, 89.4% (76/85) of participants with sustained weight gain were virally suppressed compared with 31.8% (7/22) with sustained loss, p<0.001. In participants who were lymphopaenic at baseline, an increase to normal total lymphocyte counts at 6 months was associated with an increase in CD4 count compared with participants who remained lymphopaenic, 96.2% (50/52) versus 54.8% (17/31), p<0.001. At baseline, 50.0% (110/220) had proteinuria. In participants without proteinuria from baseline to 6 months, 89.8% (79/88) were virally suppressed compared with participants with proteinuria at baseline and/or 3 months, 85.6% (77/90), those with persistent proteinuria, 30.8% (8/26), and proteinuria at 6 months only, 45.5% (5/11), p<0.001. In modified Poisson regression, the independent predictors other than CD4 cell counts for viral non-suppression at 6 months among individuals with HIV initiating on ART were BMI loss >5% from baseline to 6 months (adjusted RR 2.73, 95% CI (1.36 to 5.47)), lymphopaenia at 6 months (adjusted RR=4.54, 95% CI (2.19 to 9.39)) and proteinuria at 6 months (adjusted RR=2.63, 95% CI (1.25 to 5.54)).ConclusionsChange in BMI, total lymphocyte count and presence of proteinuria can monitor and predict ART response and may be particularly helpful in settings when CD4 counts and viral load monitoring are unavailable.
Participation in HIV vaccine trials is an essential step towards development of an effective preventive vaccine. A Phase I/II HIV vaccine trial enrolls volunteers at low risk of acquiring HIV ...infection, however a few may still become infected. Understanding the experiences of volunteers who acquired HIV infection while participating in such trials is essential for future research. Here, we describe experiences of HIV infected volunteers in Phase I/II HIV vaccine trials conducted in urban Tanzania. We used a case study design. In-depth interviews were conducted with four participants who became HIV infected during long follow-up visits after completion of vaccination schedules in a Phase I/II trial. Between 3 and 8 years after HIV positive diagnosis, each participant was interviewed at three time points within a two-year interval so as to allow for accumulation of experiences and cross-checking the emerging constructs. Data was analyzed using a qualitative data analysis framework. Analysis revealed that participation in HIV vaccine trials involves balancing controversies and the spirit of informed decision. The participants declared that they did not acquire HIV from the experimental vaccine. Disclosure of HIV status within the family was gender specific. Men were hesitant to disclose their HIV status to their sexual partners fearing for the consequences. Women's attempt to disclose their HIV status yielded negative reactions from the sexual partners. The acquired knowledge from the HIV vaccine research enabled the participants to cope with the uncertainties and their health status. The knowledge acquired during the Phase I/II HIV vaccine trial appears to be an essential resource to cope with uncertainties post research. The HIV vaccine trial implementers need to understand the challenges the volunteers may confront after the trial while coping with their health status. Longitudinal studies are essential to trace the effects of uncertainties to the individual participants.
A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial ...(PrEPVacc).
A cohort of FSWs in Dar es Salaam, Tanzania.
FSWs aged 18-45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate.
Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV.
The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.
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