DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled,double-blind phase 2b trial

BackgroundSRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania.MethodsAdolescents with a negative T- SPOT.TB^R interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA).ResultsAmong 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03).ConclusionsA three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted.Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424.     

Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania

Studies in The Gambia have provided indirect evidence that cytotoxic T lymphocytes (CTL) play a protective role against malaria in humans and recently, using allele-specific HLA class I peptide motifs, several peptide epitopes for CTL in four pre-erythrocytic Plasmodium falciparum antigens have been identified in naturally exposed Gambians. However, CTL levels were low, suggesting that boosting these low levels by immunization might provide substantial protection. In the Kilombero valley of Tanzania, malaria transmission is holoendemic and 300 times more intense than in The Gambia. We report here that several of the epitopes identified in The Gambia are also recognized in naturally exposed, partially immune Tanzanian adults and that levels of CTL are similar to or slightly higher than in Gambian subjects, despite the much higher inoculation rate. We report a new HLA-A2.1-restricted epitope from the thrombospondin-related anonymous protein (TRAP) and we demonstrate that peptide epitopes in TRAP are naturally processed for recognition by CTL from naturally exposed humans. The common allele of a variable HLA-B7-restricted epitope in the circumsporozoite protein behaved as an altered peptide ligand (APL) with respect to CTL cognate for a rarer allelic variant of this epitope, suggesting that APL antagonism may occur in natural CTL responses to P. falciparum. The moderate levels of CTL observed, even in this area of intense malaria transmission, points to the need to assess candidate vaccines aimed at increasing CTL levels.     

Ultrasound curriculum taught by first-year medical students: A four-year experience in Tanzania

BACKGROUND: Diagnostic imaging is an integral aspect of care that is often insufficient, if not altogether absent, in rural and remote regions of low to middle income countries (LMICs) such as Tanzania. The introduction of ultrasound can significantly impact treatment in these countries due to its portability, low cost, safety, and usefulness in various medical assessments. This study reviews the implementation of a four-week ultrasound course administered annually from 2013-2016 in a healthcare professional school in Mwanza, Tanzania by first-year allopathic US medical students.METHODS: Participants (n=582, over 4 years) were recruited from the Tandabui Institute of Health Sciences and Technology to take the ultrasound course. Subjects were predominantly clinical officer students, but other participants included other healthcare professional students, practicing healthcare professionals, and school employees. Data collected includes pre-course examination scores, post-course examination scores, course quiz scores, demographic surveys, and post-course feedback surveys. Data was analyzed using two-tailed t-tests and the single factor analysis of variance (ANOVA).RESULTS: For all participants who completed both the pre- and post-course examinations (n=229, 39.1% of the total recruited), there was a significant mean improvement in their ultrasound knowledge of 42.5%, P<0.01.CONCLUSION: Our data suggests that trained first-year medical students can effectively teach a point of care ultrasound course to healthcare professional students within four weeks in Tanzania. Future investigation into the level of long-term knowledge retention, impact of ultrasound training on knowledge of human anatomy and diagnostic capabilities, and how expansion of an ultrasound curriculum has impacted access to care in rural Tanzania is warranted.     

Surgical Implant Generation Network (SIGN) Fin nail versus SIGN standard intramedullary nail for distal diaphyseal femur fractures treated via retrograde approach

IntroductionSurgical fixation of distal diaphyseal femur fractures remains a major challenge in developing countries given limited availability of fluoroscopy. The Surgical Implant Generation Network (SIGN) Standard Intramedullary Nail and SIGN Fin Nail are two modalities developed to address this challenge; the Fin Nail additionally avoids needing to place proximal interlocking screws. While efficacy of the Standard Nail has been established, outcomes following fixation with the Fin Nail are unknown. In this study, we compare outcomes of distal diaphyseal femur fractures treated with each implant.MethodsA prospective cohort study was conducted from 2012 to 2013 at a single tertiary-referral center in Tanzania. Skeletally mature patients with distal diaphyseal femur fractures treated with either retrograde SIGN Standard Nail or Fin Nail were included. Patients followed-up at 6, 12, 26, and 52 weeks post-operatively. The primary outcome was all-cause reoperation. Secondary outcomes included infection, non-union, malalignment, quality of life (EQ-5D score), pain (VAS score), radiographic healing (RUST score), and function (pain with weight bearing, knee range of motion, and Squat and Smile score).Results74 (85%) of 85 enrolled patients completed the minimum 1-year follow-up. There was no difference in rate of reoperation (p = 1.00), infection (p = 1.00), limb length discrepancy (p = 0.47), non-union (p = 1.00), or coronal or sagittal malalignment (p = 1.00, p = 0.55 respectively) at 1 year. There was furthermore no difference in mean EQ-5D (p = 0.82), VAS pain score (p = 0.43), RUST score (p = 0.44), maximum knee flexion (p = 0.52) and extension (p = 1.00), or Squat and Smile function (p = 1.00) between cohorts at 1 year.DiscussionOutcomes associated with the SIGN Fin Nail are comparable to those associated with the SIGN Standard Intramedullary Nail at 1 year. The SIGN Fin Nail may be useful as an alternative to Standard locked IM nails for fixation of distal diaphyseal femur fractures.     

Anxiety and depression strongly associated with sexual risk behaviors among networks of young men in Dar es Salaam,Tanzania

This study tested the association between mental health scores and sexual risk behaviors among male members of social groups known as “camps” in Dar es Salaam, Tanzania. Anxiety and depression were measured using the HSCL-25 and condom use and sexual partner concurrency were assessed through self-report. A total of 1113 sexually active men with an average age of 27 years were included in the analyses. Higher anxiety and depression scores were significantly associated with both condom use (Anxiety AOR?=?0.58, 95% CI: 0.44, 0.77; Depression AOR?=?0.60, 95% CI: 0.47, 0.77) and concurrency (Anxiety AOR?=?2.32, 95% CI: 1.73, 3.12; Depression AOR?=?2.08, 95% CI: 1.60, 2.70). The results of this study provide information salient to the development of effective HIV prevention interventions targeting populations with high burdens of anxiety and depression. The feasibility and effect of integrating mental health promotion activities into HIV prevention interventions should be explored.     

Enhancing the routine health information system in rural southern Tanzania: successes, challenges and lessons learned

Objective To describe and evaluate the use of handheld computers for the management of Health Management Information System data. Methods Electronic data capture took place in 11 sentinel health centres in rural southern Tanzania. Information from children attending the outpatient department (OPD) and the Expanded Program on Immunization vaccination clinic was captured by trained local school‐leavers, supported by monthly supervision visits. Clinical data included malaria blood slides and haemoglobin colour scale results. Quality of captured data was assessed using double data entry. Malaria blood slide results from health centre laboratories were compared to those from the study’s quality control laboratory. Results The system took 5 months to implement, and few staffings or logistical problems were encountered. Over the following 12 months (April 2006–March 2007), 7056 attendances were recorded in 9880 infants aged 2–11 months, 50% with clinical malaria. Monthly supervision visits highlighted incomplete recording of information between OPD and laboratory records, where on average 40% of laboratory visits were missing the record of their corresponding OPD visit. Quality of microscopy from health facility laboratories was lower overall than that from the quality assurance laboratory. Conclusions Electronic capture of HMIS data was rapidly and successfully implemented in this resource‐poor setting. Electronic capture alone did not resolve issues of data completeness, accuracy and reliability, which are essential for management, monitoring and evaluation; suggestions to monitor and improve data quality are made.     

Assessment of latrine use and quality and association with risk of trachoma in rural Tanzania

The existing evidence regarding latrines and trachoma is inconclusive. Using more precise sanitation measures we examine the association between use and quality of latrines and risk of trachoma. We conducted a case-control study of 678 households (95 cases, 583 controls) in eight villages in Kongwa District, Tanzania. Case households were defined as having a sentinel child with clinical signs of trachoma. A latrine quality score was calculated based on seven indicators and case and control households were compared with respect to use and quality of latrines. Logistic regression analyses controlled for potential confounders. Latrine use was significantly greater in control households than in case households (90.4 vs. 76.8%, P=0.03). The protective effect of latrine use persisted even after controlling for household characteristics significant at P <0.20 (adjusted OR=0.56 [95% CI: 0.32-0.98]). Contrary to expectation, we did not find an inverse association between increasing latrine quality and decreasing odds of trachoma. Although latrine use in the communities was high, latrines, regardless of quality, were significantly associated with decreased risk of trachoma. These findings underscore the importance of achieving 100% latrine use in communities.