Dr
Vito Baraka
Project Title
Genetic profiling of drug resistance and population structure of plasmodium falciparum using high-throughput next generation sequencing
EDCTP Project
TMA2018CDF-2398
EDCTP Program
EDCTP2
EDCTP Project Call
Career Development Fellowship (CDF)
Host Organisation
| Department | Institution | Country |
|---|---|---|
| National Institute for Medical Research - Tanzania (NIMR) | Tanzania, United Republic of |
Current Organisation
NIMR
Current Job Title
Research Scientist
Biography
Publications
Background. Sub-Saharan Africa has the highest burden of malaria in the world. Artemisinin-based combination therapies (ACTs) have been the cornerstone in the efforts to reduce the global burden of malaria. In the effort to facilitate early detection of resistance for artemisinin derivatives and partner drugs, WHO recommends monitoring of ACT’s efficacy in the malaria endemic countries. The present systematic meta-analysis study summarises the evidence of therapeutic efficacy of the commonly used artemisinin-based combinations for the treatment of uncomplicated P. falciparum malaria in Sub-Saharan Africa after more than a decade since the introduction of the drugs.
Methods.Fifty two studies carried out from 2010 to 2020 on the efficacy of artemether-lumefantrine or dihydro-artemisinin piperaquine or artesunate amodiaquine in patients with uncomplicated P. falciparum malaria in Sub-Saharan Africa were searched for using the Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. Data was extracted by two independent reviewers. Random analysis effect was performed in STATA 13. Heterogeneity was established using I2 statistics.
Results.Based on per protocol analysis, unadjusted cure rates in malaria infected patients treated with artemether-lumefantrine (ALU), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DHP) were 89%, 94% and 91% respectively. However, the cure rates after PCR correction were 98% for ALU, 99% for ASAQ and 99% for DHP.
Conclusion.The present meta-analysis reports the overall high malaria treatment success for artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine above the WHO threshold value in Sub-Saharan Africa.
Background. It has been more than 20 years since the malaria epidemiologic shift to school-aged children was noted. In the meantime, school-aged children (5–15 years) have become increasingly more vulnerable with asymptomatic malaria prevalence reaching up to 70%, making them reservoirs for subsequent transmission of malaria in the endemic communities. Intermittent Preventive Treatment of malaria in schoolchildren (IPTsc) has proven to be an effective tool to shrink this reservoir. As of 3rd June 2022, the World Health Organization recommends IPTsc in moderate and high endemic areas. Even so, for decision-makers, the adoption of scientific research recommendations has been stifled by real-world implementation challenges. This study presents methodology, challenges faced, and mitigations used in the evaluation of the implementation of IPTsc using dihydroartemisinin-piperaquine (DP) in three councils (Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC) of Tanga Region, Tanzania so as to understand the operational feasibility and effectiveness of IPTsc on malaria parasitaemia and clinical malaria incidence.
Methods. The study deployed an effectiveness-implementation hybrid design to assess feasibility and effectiveness of IPTsc using DP, the interventional drug, against standard of care (control). Wards in the three study councils were the randomization unit (clusters). Each ward was randomized to implement IPTsc or not (control). In all wards in the IPTsc arm, DP was given to schoolchildren three times a year in four-month intervals. In each council, 24 randomly selected wards (12 per study arm, one school per ward) were chosen as representatives for intervention impact evaluation. Mixed design methods were used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive health package for schoolchildren. The study reimagined an existing school health programme for Neglected Tropical Diseases (NTD) control include IPTsc implementation.
Results. The study shows IPTsc can feasibly be implemented by integrating it into existing school health and education systems, paving the way for sustainable programme adoption in a cost-effective manner.
Conclusions. Through this article other interested countries may realise a feasible plan for IPTsc implementation. Mitigation to any challenge can be customized based on local circumstances without jeopardising the gains expected from an IPTsc programme. Trial registration clinicaltrials.gov, NCT04245033. Registered 28 January 2020, https://clinicaltrials.gov/ct2/show/NCT04245033
Background
Aedes aegypti (Diptera: Culicidae) is the main vector of the dengue virus globally. Dengue vector control is mainly based on reducing the vector population through interventions, which target potential breeding sites. However, in Tanzania, little is known about this vector's habitat productivity and insecticide susceptibility status to support evidence-based implementation of control measures. The present study aimed at assessing the productivity and susceptibility status of A. aegypti mosquitoes to pyrethroid-based insecticides in Dar es Salaam, Tanzania.Methods
An entomological assessment was conducted between January and July 2015 in six randomly selected wards in Dar es Salaam, Tanzania. Habitat productivity was determined by the number of female adult A. aegypti mosquitoes emerged per square metre. The susceptibility status of adult A. aegypti females after exposure to 0.05% deltamethrin, 0.75% permethrin and 0.05% lambda-cyhalothrin was evaluated using the standard WHO protocols. Mortality rates were recorded after 24 h exposure and the knockdown effect was recorded at the time points of 10, 15, 20, 30, 40, 50 and 60 min to calculate the median knockdown times (KDT50 and KDT95).Results
The results suggest that disposed tyres had the highest productivity, while water storage tanks had the lowest productivity among the breeding habitats Of A. aegypti mosquitoes. All sites demonstrated reduced susceptibility to deltamethrin (0.05%) within 24 h post exposure, with mortalities ranging from 86.3 ± 1.9 (mean ± SD) to 96.8 ± 0.9 (mean ± SD). The lowest and highest susceptibilities were recorded in Mikocheni and Sinza wards, respectively. Similarly, all sites demonstrated reduced susceptibility permethrin (0.75%) ranging from 83.1 ± 2.1% (mean ± SD) to 96.2 ± 0.9% (mean ± SD), in Kipawa and Sinza, respectively. Relatively low mortality rates were observed in relation to lambda-cyhalothrin (0.05%) at all sites, ranging from 83.1 ± 0.7 (mean ± SD) to 86.3 ± 1.4 (mean ± SD). The median KDT50 for deltamethrin, permethrin and lambda-cyhalothrin were 24.9-30.3 min, 24.3-34.4 min and 26.7-32.8 min, respectively. The KDT95 were 55.2-90.9 min for deltamethrin, 54.3-94.6 min for permethrin and 64.5-69.2 min for lambda-cyhalothrin.Conclusions
The productive habitats for A. aegypti mosquitoes found in Dar es Salaam were water storage containers, discarded tins and tyres. There was a reduced susceptibility of A. aegypti to and emergence of resistance against pyrethroid-based insecticides. The documented differences in the resistance profiles of A. aegypti mosquitoes warrants regular monitoring the pattern concerning resistance against pyrethroid-based insecticides and define dengue vector control strategies.
Background
Quinine or alternative artemisinin-based combination treatment (ACT) is the recommended rescue treatment for uncomplicated malaria. However, patients are often re-treated with the same ACT though it is unclear whether this is the most suitable approach. We assessed the efficacy and safety of re-treating malaria patients with uncomplicated failures with the same ACT used for the primary episode, compared with other rescue treatments.Methods
This was a bicentre, open-label, randomised, three-arm phase 3 trial done in Lisungi health centre in DR Congo, and Kazo health centre in Uganda in 2012-14. Children aged 12-60 months with recurrent malaria infection after treatment with the first-line ACT were randomly assigned to either re-treatment with the same first-line ACT, an alternative ACT, which were given for 3 days, or quinine-clindamycin (QnC), which was given for 5-7 days, following a 2:2:1 ratio. Randomisation was done by computer-generated randomisation list in a block design by country. The three treatment groups were assumed to have equivalent efficacy above 90%. Both the research team and parents or guardians were aware of treatment allocation. The primary outcome was the proportion of patients with an adequate clinical and parasitological response (ACPR) at day 28, in the per-protocol population. This trial was registered under the numbers NCT01374581 in ClinicalTrials.gov and PACTR201203000351114 in the Pan African Clinical Trials Registry.Findings
From May 22, 2012, to Jan 31, 2014, 571 children were included in the trial. 240 children were randomly assigned to the re-treatment ACT group, 233 to the alternative ACT group, and 98 to the QnC group. 500 children were assessed for the primary outcome. 71 others were not included because they did not complete the follow-up or PCR genotyping result was not conclusive. The ACPR response was similar in the three groups: 91·4% (95% CI 87·5-95·2) for the re-treatment ACT, 91·3% (95% CI 87·4-95·1) for the alternative ACT, and 89·5% (95% CI 83·0-96·0) for QnC. The estimates for rates of malaria recrudescence in the three treatment groups were similar (log-rank test: χ2=0·22, p=0·894). Artemether-lumefantrine was better tolerated than QnC (p=0·0005) and artesunate-amodiaquine (p<0·0001) in the modified intention-to-treat analysis. No serious adverse events were observed. The most common adverse events reported in the re-treatment ACT group were anorexia (31 [13%] of 240 patients), asthenia (20 [8%]), coughing (16 [7%]), abnormal behaviour (13 [5%]), and diarrhoea (12 [5%]). Anorexia (13 [6%] of 233 patients) was the most frequently reported adverse event in the alternative ACT group. The most commonly reported adverse events in the QnC group were anorexia (12 [12%] of 98 patients), abnormal behaviour (6 [6%]), asthenia (6 [6%]), and pruritus (5 [5%]).Interpretation
Re-treatment with the same ACT shows similar efficacy as recommended rescue treatments and could be considered for rescue treatment for Plasmodium falciparum malaria. However, the effect of this approach on the selection of resistant strains should be monitored to ensure that re-treatment with the same ACT does not contribute to P falciparum resistance.Funding
Fonds Wetenschappelijk Onderzoek, Vlaamse Interuniversitaire Raad-Universitaire Ontwikkelings Samenwerking, European and Developing Countries Clinical Trials Partnership, and the Belgian Technical Cooperation-Programme d'Etudes et d'Expertises-in the Democratic Republic of Congo.