Amos Y. Massele

Malaria rapid testing by community health workers is effective and safe for targeting malaria treatment: randomised cross-over trial in Tanzania.

Background Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients. Methodology/Principal Findings Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029–0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8–97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients. Conclusions/Significance RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa. Trial registration ClinicalTrials.gov NCT00301015

Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype.

The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize the CYP2D6 substrate debrisoquine with 59% of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20% in Caucasians. This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6 gene mutations analysed for in this study. As many as 7% poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6 alleles. The majority among the group of poor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2D locus to that of Zimbabweans rather than to that of Ethiopians. The defective alleles CYP2D6*3, *4, *5 and *6 were found at low frequencies (0%, 1%, 6%, 0%, respectively), whereas the CYP2D6*17 allele causing an enzyme with altered specificity was common (allele frequency = 17%). It is concluded that the CYP2D6 genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates.

Impact of training in clinical and microscopy diagnosis of childhood malaria on antimalarial drug prescription and health outcome at primary health care level in Tanzania: A randomized controlled trial

BackgroundPrescribing antimalarial medicines based on parasite confirmed diagnosis of malaria is critical to rational drug use and optimal outcome of febrile illness. The impact of microscopy-based versus clinical-based diagnosis of childhood malaria was assessed at primary health care (PHC) facilities using a cluster randomized controlled training intervention trial.MethodsSixteen PHC facilities in rural Tanzania were randomly allocated to training of health staff in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children presenting at these facilities were assessed, treated and scheduled for follow up visit after 7 days. Blood smears on day 0 were only done in Arm-I but on Day 7 in all arms. Primary outcome was antimalarial drug prescription. Other outcomes included antibiotic prescription and health outcome. Multilevel regression models were applied with PHC as level of clustering to compare outcomes in the three study arms.ResultsA total of 973, 1,058 and 1,100 children were enrolled in arms I, II and III, respectively, during the study period. Antimalarial prescriptions were significantly reduced in Arm-I (61.3%) compared to Arms-II (95.3%) and III (99.5%) (both P < 0.001), whereas antibiotic prescriptions did not vary significantly between the arms (49.9%, 54.8% and 34.2%, respectively). In Arm-I, 99.1% of children with positive blood smear readings received antimalarial prescriptions and so did 11.3% of children with negative readings. Those with positive readings were less likely to be prescribed antibiotics than those with negative (relative risk = 0.66, 95% confidence interval: 0.55, 0.72). On day 7 follow-up, more children reported symptoms in Arm-I compared to Arm-III, but fewer children had malaria parasitaemia (p = 0.049). The overall sensitivity of microscopy reading at PHC compared to reference level was 74.5% and the specificity was 59.0% but both varied widely between PHCs.ConclusionMicroscopy based diagnosis of malaria at PHC facilities reduces prescription of antimalarial drugs, and appears to improve appropriate management of non-malaria fevers, but major variation in accuracy of the microscopy readings was found. Lack of qualified laboratory technicians at PHC facilities and the relatively short training period may have contributed to the shortcomings.Trial registrationThis study is registered at Clinicaltrials.gov with the identifier NCT00687895.

Case management of malaria in under-fives at primary health care facilities in a Tanzanian district

OBJECTIVEu2003To study case management of malaria in children under 5u2003years of age at primary health care facilities in Kibaha district, Tanzania and to evaluate the accuracy of self‐reported mothers/guardians information on chloroquine use in children.

Evaluation of the quality of amodiaquine and sulphadoxine/pyrimethamine tablets sold by private wholesale pharmacies in Dar Es Salaam Tanzania

Objective: There are several independent reports in Tanzania of treatment failures with commercially available sulphadoxine/pyrimethamine (SP) and amodiaquine (AQ) brands. The aim of this work was to assess the quality of SP and AQ tablets marketed by wholesale pharmacies in Dar Es Salaam, Tanzania.

A Household Survey of Source, Availability, and Use of Antimalarials in a Rural Area of Tanzania

The source, availability, and use of antimalarial drugs in a rural community in the Kibaha district of Tanzania were assessed. Using questionnaires, the heads of households and mothers/guardians of children under five years of age in 1000 randomly selected households were interviewed, and an inventory of antimalarials at all drug stores and shops in the area was carried out. The majority of the drugs stocked by both households and mothers/guardians were antimalarials, exclusively chloroquine. Only 20.1% of the mothers/guardians knew the correct pediatric dose regimen of the chloroquine syrup which they stocked the most. In contrast, 70.4% of the mothers/guardians stated the correct adult dose of chloroquine tablets. They had significantly (p < 0.025) higher mean ages than those who stated the dose incorrectly. Similarly, 78.6% of heads of households stated the correct adult dose of chloroquine tablets, and those with more education had better knowledge of dose regimens (p < 0.001). Drug stores were the main sources of malaria treatment for both the heads of households (72.2%) and the mothers/guardians (89.4%). Lack of drugs at public health facilities, as stated by more than 85.6% of the mothers/guardians, is a possible reason for this. Only four of the drug store sellers had professional training. Most malaria treatment in children occurs in the home and, thus, poor knowledge of pediatric chloroquine regimen by the mothers/guardians is of great concern. A simplified dose regimen, particularly the pediatric formulation for mothers/guardians with limited education, should be developed. As these caregivers interact with the public and private health facilities, the quality of malaria management, including instructions given to them, needs to be assessed.

A Study of Prescribing Patterns with Special Reference to Drug Use Indicators in Dar es Salaam Region, Tanzania

Drug prescribing patterns were studied in 720 retrospective and 779 prospective outpatient prescriptions from 20 dispensaries in Dar es Salaam region, and these revealed a mean drug exposure of 2.0 and 2.3, respectively. The percentage of patients leaving the dispensaries with no prescribed drugs was 1.3% and 0.7%, respectively. Prescriptions containing antibiotics were 36.8% (retrospective) and 39.8% (prospective), while injections accounted for 24.6% and 34% of the total encounters, respectively. Over 70% of prescriptions conformed to the Tanzania essential drug list (EDP) and/or standard treatment guidelines and consisted of 83.9% and 79.1% generic prescriptions, respectively. Interestingly, only 15% of the surveyed dispensaries had an EDP book and/or calendar. Despite the consulting and dispensing times being short (2.98 min and 77.7 s, respectively), 70% of the patients could remember the dosing instructions. Only 64% of the patients had a minimum physical examination.

Comparative bioavailability of oral sugar-coated and plain formulation of chloroquine phosphate marketed in Tanzania.

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (DawaquinR) and a plain formulation (ShellyquineR) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL−1 h) and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 ± 833 ng mL−1 h and 162 ± 14 ng/mL, respectively. The AUC and Cpmax for Dawaquin were 2060 ± 339 ng mL−1 h and 56.6 ± 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.

Existence of antimalarial formulations with low bioavailability in Tanzania

The main objective of this work was to assess the relative bioavailability of two tablet formulations containing sulfadoxine/pyrimethamine (SP) and marketed in Tanzania. Twelve healthy volunteers were randomized to receive a single oral dose of three SP tablets each containing 500 mg sulfadoxine (SDX) and 25 mg pyrimethamine (PYR) in a form of either A (a locally manufactured SP tablet formulation, manufactured by a local pharmaceutical industry in Tanzania) or B (Fansidar®, Hoffmann La Roche, Basel, Switzerland, an innovators SP) after an overnight fasting. Serial blood samples (100 μL) were collected from a finger prick in duplicate up to 10 days and dried on Whatman® filter paper. The samples were assayed for SDX and PYR using high-performance liquid chromatographic methods. Pharmacokinetic parameters of SDX and PYR were estimated by single compartment method. The pharmacokinetics of formulation A - maximum plasma concentration, the areas under the plasma concentration - time curve and the relative bioavailability (A versus B) were significantly lower than those of formulation B (P<0.1). These observed differences indicate bioinequivalence between the two products.

Comparative in vitro and in vivo study of a sugar-coated chloroquine preparation marketed in Tanzania versus an ordinary brand

Objective: To investigate the absorption and the quality of a sugar‐coated chloroquine (CQ) marketed in Tanzania.