Tumaini University Makumira

About: Tumaini University Makumira is a education organization based out in Arusha, Tanzania. It is known for research contribution in the topics: Population & Tanzania. The organization has 111 authors who have published 147 publications receiving 6045 citations.

Differentiating the pathologies of cerebral malaria by postmortem parasite counts.

Abstract: To study the pathogenesis of fatal cerebral malaria, we conducted autopsies in 31 children with this clinical diagnosis. We found that 23% of the children had actually died from other causes. The remaining patients had parasites sequestered in cerebral capillaries, and 75% of those had additional intra- and perivascular pathology. Retinopathy was the only clinical sign distinguishing malarial from nonmalarial coma. These data have implications for treating malaria patients, designing clinical trials and assessing malaria-specific disease associations.

Evaluation of In-Hospital Management for Febrile Illness in Northern Tanzania before and after 2010 World Health Organization Guidelines for the Treatment of Malaria

Abstract: In 2010, the World Health Organization (WHO) published updated guidelines emphasizing and expanding recommendations for a parasitological confirmation of malaria before treating with antimalarials. This study aimed to assess differences in historic (2007–2008) (cohort 1) and recent (2011–2012) (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania. We analyzed data from two prospective cohort studies that enrolled febrile adolescents and adults aged $13 years. All patients received quality-controlled aerobic blood cultures and malaria smears. We compared patients’ discharge diagnoses, treatments, and outcomes to assess changes in the treatment of malaria and bacterial infections. In total, 595 febrile inpatients were enrolled from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in cohort 2 (p = 0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear-negative patients in cohort 1 and 97 (50.5%) of 192 smearnegative patients in cohort 2 (p = 0.794). Bacteremia was diagnosed from standard blood culture in 58 (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in cohort 2 (p = 0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive blood culture received antibacterials compared to 16 (88.9%) of 18 patients in cohort 2 (p = 0.094). In cohort 1, 43 (10.8%) of the 399 patients with known outcomes died during hospitalization compared with 12 (6.2%) deaths among 193 patients in cohort 2 (p = 0.073). In a setting of low malaria transmission, a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite updated WHO guidelines on malaria treatment. Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice.

High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

Abstract: Summary Background Tuberculosis is the world's leading infectious disease killer We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis Methods We did a randomised controlled, open-label trial with a multi-arm, multi-stage design The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15–20 mg/kg ethambutol) Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation The primary endpoint was time to culture conversion in liquid media within 12 weeks Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat) Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p Findings Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm) Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1·78; 95% CI 1·22–2·58, p=0·003), but not in other experimental arms There was no difference in any of the groups in time to culture conversion on solid media 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm 45 (12%) of 365 patients reported grade 3–5 adverse events, with similar proportions in each arm Interpretation A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost Funding The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC)

Invasive Non-Typhi Salmonella Disease in Africa

Abstract: Invasive non-Typhi Salmonella is endemic to sub-Saharan Africa, where it is a leading cause of bloodstream infection. Some host risk factors have been established, but little is known about environmental reservoirs and predominant modes of transmission, so prevention strategies are underdeveloped. Although foodborne transmission from animals to humans predominates in high-income countries, it has been postulated that transmission between humans, both within and outside health care facilities, may be important in sub-Saharan Africa. Antimicrobial resistance to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol is common among non-Typhi Salmonella strains; therefore, wider use of alternative agents may be warranted for empirical therapy. Development of vaccines targeting the leading invasive non-Typhi Salmonella serotypes Typhimurium and Enteritidis is warranted. The clinical presentation of non-Typhi Salmonella bacteremia is nonspecific and, in the absence of blood culture, may be confused with other febrile illnesses, such as malaria. Much work remains to be done to understand and control invasive non-Typhi Salmonella disease in sub-Saharan Africa.

Predictors of Incomplete Adherence, Virologic Failure, and Antiviral Drug Resistance among HIV-Infected Adults Receiving Antiretroviral Therapy in Tanzania

Abstract: Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence virologic failure and antiviral drug resistance is essential to achieving long-term success. A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level > 400 copies/mL; for patients with an HIV RNA level > 1000 copies/mL genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR] 19.8; P < .01) and the proportion of months receiving self-funded treatment (AOR 23.5; P = .04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR 3.6; P = .03) and the proportion of months receiving self-funded antiretroviral therapy (AOR 13.0; P = .02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR 0.10; P = .04). Self-funded treatment was associated with incomplete adherence and virologic failure and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure. (authors)