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Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasite K13 gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGA version 11 software. The data were analysed using STATA version 15, and the Mann‒Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method and pfkelch13 mutations. The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients. P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. The K13 mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearance p = 0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730). There was a high prevalence of day 3 P. falciparum among malaria patients treated using artemether-lumefantrine. We conclude the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Angwe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Malaria treatment is faced with the challenge of access, affordability, availability, and quality of antimalarial medicines. Affordable medicines facility-malaria (AMFm) program and subsequently Co-payment mechanism were developed to help increase access to quality assured Artemisinin-based combination therapies (ACTs) in seven countries in sub-Saharan Africa. We explored through a qualitative study, experience of healthcare personnel on Co-payment mechanism and the implication on its use in private drug outlets in Uganda., Method: Private drug outlets that reported stocking antimalarial agents in moderate-to-high and low malaria transmission settings were purposively selected for inclusion in the study. In each drug outlet, data was collected from a pharmacist/dispenser through key informant interview. The interview was done using a key informant interview guide which covered the following areas, (i) sociodemographic characteristics, ii) awareness of healthcare personnel on the co-payment mechanism, (iii) awareness of healthcare personnel on quality assured artemisinin combination therapies (QAACT), (iv) antimalarial stocking in private drug outlets, (v) antimalarial dispensing prices, (vi) considerations made while stocking, and pricing antimalarial agents, vii) challenges in antimalarial dispensing, and (viii) access to antimalarial agents in private drug outlets. Data was managed using Atlas.ti and analyzed using framework methodology., Results: Data was collected from 25 key informants (12 pharmacists and 13 dispensers). Five themes emerged following data analysis, (i) antimalarial stocking influenced by price and client demand, (ii) access and purchasing behavior of drug outlet clients, (iii) basis of dispensing antimalarial agents in private drug outlets, (iv) awareness of QAACT, and (v) awareness of Co-payment mechanism. None of the study participants was aware of the existence of Co-payment mechanism and QAACT in the private sector. Duocotecin brand of ACTs was the most mentioned and dispensed ACT among the study participants in private drug outlets. Nearly all the pharmacists/dispensers said that many clients who request to purchase ACTs don't come with a prescription and prefer buying cheaper antimalarial agents. Study participants reported stocking and selling both ACTs and non-ACT antimalarial agents in the drug outlets. Pharmacists/dispensers in the drug outlets reported that most clients could not afford buying a full dose of an ACT. None of the study participants considered using Co-payment mechanism while stocking ACTs in the drug outlets., Conclusion: There is lack of awareness and utilization of Co-payment mechanism in stocking, pricing, and dispensing of ACTs among pharmacists/dispensers in private drug outlets in Uganda. The antimalarial dispensing in drug outlets was mostly based on prescriptions, clients' preferences, and medicine affordability. The Ministry of Health needs to create demand for Co-payment mechanism through public awareness campaigns, training of healthcare personnel and behavior change communication in the private sector., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Ocan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Malaria treatment in sub-Saharan Africa is faced with challenges including unreliable supply of efficacious agents, substandard medicines coupled with high price of artemisinin-based combinations. This affects access to effective treatment increasing risk of malaria parasite resistance development and adverse drug events. This study investigated access to quality-assured artemisinin-based combination therapy (QAACT) medicines among clients of selected private drug-outlets in Uganda., Methods: This was a cross sectional study where exit interviews were conducted among clients of private drug outlets in low and high malaria transmission settings in Uganda. This study adapted the World Health Organization/Health Action International (WHO/HAI) standardized criteria. Data was collected using a validated questionnaire. Data entry screen with checks was created in Epi-data ver 4.2 software and data entered in duplicate. Data was transferred to STATA ver 14.0 and cleaned prior to analysis. The analysis was done at 95% level of significance., Results: A total of 1114 exit interviews were conducted among systematically sampled drug outlet clients. Over half, 54.9% (611/1114) of the participants were males. Majority, 97.2% (1083/1114) purchased an artemisinin-based combination anti-malarial. Most, 55.5% (618/1114) of the participants had a laboratory diagnosis of malaria. Majority, 77.9% (868/1114) of the participants obtained anti-malarial agents without a prescription. Less than a third, 27.7% (309/1114) of the participants obtained a QAACT. Of the participants who obtained QAACT, more than half 56.9% (173/309) reported finding the medicine expensive. The predictors of accessing a QAACT anti-malarial among drug outlet clients include type of drug outlet visited (aPR = 0.74; 95%CI 0.6, 0.91), not obtaining full dose (3-day treatment) of ACT (aPR = 0.49; 95%CI 0.33, 0.73), not finding the ACT expensive (aPR = 1.24; 95%CI 1.03, 1.49), post-primary education (aPR = 1.29; 95%CI 1.07,1.56), business occupation (aPR = 1.24; 95%CI 1.02,1.50) and not having a prescription (aPR = 0.76; 95%CI 0.63, 0.92)., Conclusion: Less than a third of the private drug outlet clients obtained a QAACT for management of malaria symptoms. Individuals who did not find artemisinin-based combinations to be expensive were more likely to obtain a QAACT anti-malarial. The Ministry of Health needs to conduct regular surveillance to monitor accessibility of QAACT anti-malarial agents under the current private sector copayment mechanism., (© 2024. The Author(s).)

Background: Malaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in private sector. However, availability and affordability are major barriers to access to effective treatment. The private sector copayment mechanism in Uganda aims to increase availability and affordability of antimalarial agents. Our study assessed availability, price, and market share of quality assured artemisinin-based combination therapies (QAACTs) in private drug outlets in selected districts during the implementation of copayment mechanism., Methods: This was a cross-sectional survey of anti-malarial agents in private drug outlets in in selected moderate-to-high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings. Following the World Health Organization/Health Action International (WHO/HAI) criteria, an audit of the antimalarial agents was done using a checklist to determine availability, price, and market share of QAACTs. Data were entered in Epi-data and analyzed in STATA ver 14.0 at 95% confidence level., Results: A total of twenty-eight (28) private drug outlets (pharmacies and drug shops) were included in the survey. One in seven (20/144: 95%CI: 9.1, 20.6) of the antimalarial agents in private drug outlets were quality assured artemisinin-based combination therapies (QAACT). Artemether-lumefantrine (AL), 8.9% (11/124) and Artesunate-Amodiaquine (AQ), 7.3% (9/124) were the only QAACTs present in the drug outlets at the time of the survey. The majority, 86.1%% (124/144) of antimalarial agents present in stock in the drug outlets were artemisinin based. The most common, 38.9% (56/144) ACT in the drug outlets was Dihydroartemisinin-Piperaquine (DHP). Most, 69.4% (100/144) of the antimalarial agents were in high malaria transmission settings. The cost of ACT antimalarial agents is high in the country, USD 1.4 (Artemether-Lumefantrine, AL), USD 2.4 (Dihydroartemisinin-Piperaquine, DP), the first line and second-line agents respectively for treatment of uncomplicated malaria in Uganda. There was a statistically significant difference between the dispensing price of 'Green leaf' ACTs (QAACT) and the recommended price (p<0.001). Predictors of availability of QAACT in private drug outlets include pharmacy drug outlet (aPR:0.4; 95%CI: 0.2, 0.9) and dispensing price more than 3000UGX (USD 0.83) (aPR: 0.4, 95%CI: 0.1, 0.51)., Conclusion: Quality assured artemisinin-based combination therapies (QAACTs) are not common in private drug outlets in selected districts in Uganda. All the drug outlets had at least one ACT antimalarial agent present on the day of the survey. The dispensing price of QAACTs was significantly higher than the recommended markup price. There is need for awareness creation, surveillance, and monitoring of the implementation of Copayment mechanism in the country., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2024 Ocan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The risk of widespread resistance to artemisinin-based combination therapy (ACT) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACT in the management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda., Methods: This was a qualitative study in which data was collected from healthcare personnel in hospitals using key informant interviews. The key informant interview guide was developed, pre-tested prior to use and covered the following areas, (i) sociodemographic characteristics, (ii) malaria diagnosis (clinical and parasite based), (iii) quality-assured artemisinin-based combination therapy, (iv) malaria patient follow-up, (v) artemisinin resistance, (vi) anti-malarial self-medication. Data was entered in Atlas.ti ver 9.0 and analysis done following a framework criterion., Results: A total of 22 respondents were interviewed of which 16 (72.7%) were clinicians. Majority, 81.8% (18/22) of the respondents were male. The following themes were developed from the analysis, malaria diagnosis (procedures and challenges), use of malaria laboratory test results, malaria treatment in hospitals, use of quality assured ACT (QAACT) in malaria treatment, and efficacy of ACT in malaria treatment., Conclusion: Most healthcare personnel-initiated malaria treatment after a positive laboratory test. Cases of malaria patients who report remaining symptomatic after prior use of ACT exist especially in high malaria transmission settings in Uganda. There is need for regular monitoring of artemisinin resistance emergence and spread in the country., (© 2023. The Author(s).)

Introduction: With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally., Methods and Analysis: The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE's risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC 50; Ring Stage Assay, RSA 0-3 hou; Trophozoite Survival Assay, TSA 50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213)., Prospero Registration Number: CRD42022367073., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether-lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed., Methods: This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography-mass spectrometry (LC-MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90-110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher's exact test of independence at 95% level of significance., Results: A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being 'Green leaf'. Overall prevalence of substandard quality artemether-lumefantrine was 18.9% (14/74; 95% CI: 11.4-29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (< 90%) artemether content. All the samples passed visual inspection and dissolution tests., Conclusion: Artemether-lumefantrine agents, the recommended first-line treatment for uncomplicated malaria with APIs outside the recommended pharmacopeial content assay limit is common especially in high malaria transmission settings. There is need for continuous surveillance and monitoring of the quality of artemisinin-based anti-malarials across the country by the drug regulatory agency., (© 2023. The Author(s).)

Background: The in-utero transfer of malaria specific IgG to the fetus in Plasmodium falciparum infected pregnant women potentially plays a role in provision of immune protection against malaria in the first birth year. However, the effect of Intermittent Prophylactic Treatment in Pregnancy (IPTp) and placental malaria on the extent of in-utero antibody transfer in malaria endemic regions like Uganda remain unknown. The aim of this study was thus to establish the effect of IPTp on in-utero transfer of malaria specific IgG to the fetus and the associated immune protection against malaria in the first birth year of children born to mothers who had P. falciparum infection during pregnancy in Uganda., Methods: We screened a total of 637 cord blood samples from a double blinded randomized clinical trial on Sulfadoxine-Pyrimethamine (SP) and Dihydroartemisinin-Piperaquine (DP) IPTp in a Ugandan birth cohort; study conducted from Busia, Eastern Uganda. Luminex assay was used to measure the cord levels of IgG sub-types (IgG1, IgG2, IgG3 and IgG4) against 15 different P. falciparum specific antigens, with tetanus toxoid (t.t) as a control antigen. Man-Whitney U test (non-parametric) in STATA (ver15) was used in statistical analysis of the samples. In addition, Multivariate cox regression analysis was used to determine the effect of maternal transfer of IgG on the incidence of malaria in the first birth year of children under study., Results: Mothers on SP expressed higher levels of cord IgG4 against erythrocyte binding antigens (EBA140, EBA175 and EBA181) (p<0.05). Placental malaria did not affect cord levels of IgG sub-types against selected P. falciparum specific antigens (p>0.05). Children who expressed higher levels (75th percentile) of total IgG against the six key P. falciparum antigens (Pf SEA, Rh4.2, AMA1, GLURP, Etramp5Ag1 and EBA 175) had higher risk of malaria in the first birth year; AHRs: 1.092, 95% CI: 1.02-1.17 (Rh4.2); 1.32, 95% CI: 1.00-1.74 (PfSEA); 1.21, 95%CI: 0.97-1.52 (Etramp5Ag1); 1.25, 95%CI: 0.98-1.60 (AMA1); 1.83, 95%CI: 1.15-2.93 (GLURP) (GLURP), and 1.35,; 95%CI: 1.03-1.78 (EBA175). Children born to mothers categorized as poorest had the highest risk of malaria infections in the first birth year (AHR: 1.79, 95% CI: 1.31-2.4). Children born to mothers who had malaria infections during gestation had higher risk of getting malaria in the first birth year (AHR 1.30; 95%CI: 0.97-1.7)., Conclusion: Malaria prophylaxis in pregnant mothers using either DP or SP does not affect expression of antibodies against P. falciparum specific antigens in the cord blood. Poverty and malaria infections during pregnancy are key risk factors of malaria infections in the first birth year of growth of children. Antibodies against P. falciparum specific antigens does not protect against parasitemia and malaria infections in the first birth year of children born in malaria endemic areas., Competing Interests: All Authors have declared that no competing interests exists., (Copyright: © 2023 Okek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Uganda, Artemether-Lumefantrine and Artesunate are recommended for uncomplicated and severe malaria respectively, but are currently threatened by parasite resistance. Genetic and epigenetic factors play a role in predisposing Plasmodium falciparum parasites to acquiring Pfkelch13 (K13) mutations associated with delayed artemisinin parasite clearance as reported in Southeast Asia. In this study, we report on the prevalence of mutations in the K13, pfmdr-2 (P. falciparum multidrug resistance protein 2), fd (ferredoxin), pfcrt (P. falciparum chloroquine resistance transporter), and arps10 (apicoplast ribosomal protein S10) genes in Plasmodium falciparum parasites prior to (2005) and after (2013) introduction of artemisinin combination therapies for malaria treatment in Uganda. A total of 200 P. falciparum parasite DNA samples were screened. Parasite DNA was extracted using QIAamp DNA mini kit (Qiagen, GmbH, Germany) procedure. The PCR products were sequenced using Sanger dideoxy sequencing method. Of the 200 P. falciparum DNA samples screened, sequencing for mutations in K13, pfmdr-2, fd, pfcrt, arps10 genes was successful in 142, 186, 141, 128 and 74 samples respectively. Overall, we detected six (4.2%, 6/142; 95%CI: 1.4-7.0) K13 single nucleotide polymorphisms (SNPs), of which 3.9% (2/51), 4.4% (4/91) occurred in 2005 and 2013 samples respectively. All four K13 SNPs in 2013 samples were non-synonymous (A578S, E596V, S600C and E643K) while of the two SNPs in 2005 samples, one (Y588N) is non-synonymous and the other (I587I) is synonymous. There was no statistically significant difference in the prevalence of K13 (p = 0.112) SNPs in the samples collected in 2005 and 2013. The overall prevalence of SNPs in pfmdr-2 gene was 39.8% (74/186, 95%CI: 25.1-50.4). Of this, 4.2% (4/95), 76.9% (70/91) occurred in 2005 and 2013 samples respectively. In 2005 samples only one SNP, Y423F (4.2%, 4/95) was found while in 2013, Y423F (38.5%, 35/91) and I492V (38.5%, 35/91) SNPs in the pfmdr-2 gene were found. There was a statistically significant difference in the prevalence of pfmdr-2 SNPs in the samples collected in 2005 and 2013 (p<0.001). The overall prevalence of arps10 mutations was 2.7% (2/72, 95%CI: 0.3-4.2). Two mutations, V127M (4.5%: 1/22) and D128H (4.5%: 1/22) in the arps10 gene were each found in P. falciparum parasite samples collected in 2013. There was no statistically significant difference in the prevalence of arps10 SNPs in the samples collected in 2005 and 2013 (p = 0.238). There were more pfmdr-2 SNPs in P. falciparum parasites collected after introduction of Artemisinin combination therapies in malaria treatment. This is an indicator of the need for continuous surveillance to monitor emergence of molecular markers of artemisinin resistance and its potential drivers in malaria affected regions globally., Competing Interests: The authors have declared that no competing interests exist.

Background: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use., Methods: A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I 2 -statistic., Results: A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC 50  < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I 2  > 95%)., Conclusion: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Background: Malaria remains one of the leading causes of morbidity and mortality in most low- and middle-income countries. Chloroquine is a previously cheap and effective antimalarial agent whose loss to resistance resulted in more than doubling of malaria-related mortality in malaria-endemic countries. Recently, chloroquine sensitivity is re-emerging among Plasmodium falciparum parasites which gives hope for malaria control and treatment efforts globally. The aim of the current review is to establish the prevalence of chloroquine resistance alleles among P. falciparum parasites in malaria-endemic areas after change in malaria treatment policy., Methods/design: The articles will be obtained from search of MEDLINE via PubMed, SCOPUS, and EMBASE data bases. The Mesh terms will be used in article search. Boolean operators ("AND," "OR") will be used in article search. The article search will be done independently by two librarians. The PRISMA-P statement will be used to guide the conduct and reporting of the systematic review. STREGA guideline will be used in developing data abstraction form for the review. Data abstraction will be done by two independent reviewers, Kappa statistic will be calculated, and any discrepancies resolved by discussion. Data analysis will be done using STATA ver 13.0. The level of heterogeneity in the articles will be established by using the I 2 -statistic. Publication bias will be assessed using funnel plot. Random effects analysis will be used., Discussion: The review seeks to establish the extent of chloroquine resistance reversal in malaria-endemic countries. The evidence generated from this review will help guide policy makers on the potential re-emerging role of chloroquine in malaria treatment., Systematic Review Registration: The systematic review protocol has been registered in PROSPERO with registration number CRD42018083957.