Dapsone 100mg / Pyrimethamine 12.5mg tablets

Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the review, 21 from sSA and seven from India. On analysis, Artemether + lumefantrine (AL) and artesunate + sulfadoxine-pyrimethamine (AS + SP) are the main ACT in African and Indian regions with a 28-day efficacy range of 54.3-100% for AL and 63-100% for AS + SP respectively. It was observed that mutations in the Pfcrt (76T), Pfdhfr (51I, 59R, 108N), Pfdhps (437G) and Pfmdr1 (86Y, 184F, 1246Y) genes were involved in TF, which varied with respect to ACTs. Based on studies that have genotyped the Pfk13 gene, the reported TF cases, were mainly linked with mutations in genes associated with resistance to ACT partner drugs; indicating that the protection of the partner drug efficacy is crucial for maintaining the efficacy of ACT. This review reveals that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations (i.e., 476I, 539T and 561H) in circulation in these two regions. Also, the role of PfATPase6 in ART resistance is controversial still, while P. falciparum plasmepsin 2 (Pfpm2) in piperaquine (PPQ) resistance and dihydroartemisinin (DHA) + PPQ failures is well documented in Southeast Asian countries but studied less in sSA. Hence, there is a need for continuous molecular surveillance of Pfk13 mutations for emergence of artemisinin (ART) resistance in these countries.

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BackgroundSevere anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia.MethodsThis analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged FindingsOur search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I2=0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], pInterpretationIn malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity.FundingThe Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network.

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BackgroundOcular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual loss by controlling infection and inflammation. However, there remains disagreement regarding optimal antibiotic therapy for OT. Therefore, this systematic review and meta-analysis were performed to determine the effects and safety of existing antibiotic treatment regimens for OT.MethodsMEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, LILACS, WHO International Clinical Trials Registry Platform portal, ClinicalTrials.gov, and Gray Literature in Europe ("OpenGrey") were searched for relevant studies; manual searches of reference lists were performed for studies identified by other methods. All published and unpublished randomized controlled trials that compared antibiotic schemes known to be effective in OT at any dosage, duration, and administration route were included. Studies comparing antibiotics with placebo were excluded. This review followed standard methodological procedures recommended by the Cochrane group.ResultsTen studies were included in the narrative summary, of which four were included for quantitative synthesis (meta-analysis). Interventions were organized into three groups: intravitreal clindamycin versus pyrimethamine + sulfadiazine, trimethoprim + sulfamethoxazole versus other antibiotics, and other interventions. The first comparison favored intravitreal clindamycin (Mean difference (MD) = 0.10 logMAR; 95% confidence interval = 0.01 to 0.22). However, this finding lacks clinical relevance. Other outcomes showed no statistically significant differences between the treatment groups. In general, the risk of performance bias was high in evaluated studies, and the quality of the evidence found was low to very low.ConclusionsNo antibiotic scheme was superior to others, and the selection of a treatment regimen depends on multiple factors; therefore, treatment should be chosen based on safety, sulfa allergies, and availability.

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BackgroundAn estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa.MethodsThis will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12-18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing.DiscussionAt the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022.Trial registrationThe trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021.

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