scholarly journals Chloroquine and Sulfadoxine–Pyrimethamine Resistance in Sub-Saharan Africa—A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra T. Roux ◽  
Leah Maharaj ◽  
Olukunle Oyegoke ◽  
Oluwasegun P. Akoniyon ◽  
Matthew Adekunle Adeleke ◽  
...  

Malaria is a great concern for global health and accounts for a large amount of morbidity and mortality, particularly in Africa, with sub-Saharan Africa carrying the greatest burden of the disease. Malaria control tools such as insecticide-treated bed nets, indoor residual spraying, and antimalarial drugs have been relatively successful in reducing the burden of malaria; however, sub-Saharan African countries encounter great challenges, the greatest being antimalarial drug resistance. Chloroquine (CQ) was the first-line drug in the 20th century until it was replaced by sulfadoxine–pyrimethamine (SP) as a consequence of resistance. The extensive use of these antimalarials intensified the spread of resistance throughout sub-Saharan Africa, thus resulting in a loss of efficacy for the treatment of malaria. SP was replaced by artemisinin-based combination therapy (ACT) after the emergence of resistance toward SP; however, the use of ACTs is now threatened by the emergence of resistant parasites. The decreased selective pressure on CQ and SP allowed for the reintroduction of sensitivity toward those antimalarials in regions of sub-Saharan Africa where they were not the primary drug for treatment. Therefore, the emergence and spread of antimalarial drug resistance should be tracked to prevent further spread of the resistant parasites, and the re-emergence of sensitivity should be monitored to detect the possible reappearance of sensitivity in sub-Saharan Africa.

2020 ◽  
Author(s):  
Gideon Yakusak Benjamin ◽  
Helen Ileigo Inabo ◽  
Hassan Isa Doko Muhammad ◽  
Busayo O Olayinka

Abstract Background Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. The emergence of drug resistance, particularly among P. falciparum strains, has been a major contributor to the global burden of malaria. This research was aimed at detecting genetic markers associated with antimalarial drug resistance and assessing the distribution of haemoglobin genotypes among malaria patients in of Kaduna State, Nigeria.Methods Three hundred (300) blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. A structured questionnaire was used to obtain relevant data from the study participants. The samples were screened for malaria parasites by microscopy and malaria rapid diagnostic test kit. Deoxyribonucleic acid was extracted from one third of the malaria positive samples, and Polymerase Chain Reaction (PCR) was used for detection of the drug resistance genes. Pfcrt, pfmdr1, pfdhfr, pfdhps and pfatpase6 genes were detected at expected amplicon sizes from the malaria positive samples. The pfatpase6 PCR amplicons were sequenced and a phylogenetic tree was created using MEGA X to determine their relatedness to published sequences.Results Pfcrt (80%) had the highest prevalence, followed by pfdhfr (60%), pfmdr1 (36%) and pfdhps (8%). Pfatpase6 was also detected in 73.3% of the samples. The phylogenetic tree showed that all the pfatpase6 gene sequences (both the ones from this study and those published in NCBI Genbank) had the same origin and were closely related. However, the sequences from NCBI Genbank were from one clade; arising from a common ancestor (monophyletic) thus they were more closely related to themselves, than to the pfatpase6 sequences obtained in this study. Of all the malaria positive participants, those with HbAA (73%) haemoglobin genotype had the highest percentage followed by HbAS (23%), HbAC (3%) and HbSS (1).Conclusion We detected Plasmodium falciparum genes associated with drug resistance to commonly used antimalarials in the study area. Expression of these genes could have serious consequences in the treatment of malaria. Persons with HbAS, HbAC and HbSS may enjoy some protection from falciparum malaria than those with HbAA.


2008 ◽  
Vol 7 (1) ◽  
Author(s):  
Jean-Pierre Van geertruyden ◽  
Joris Menten ◽  
Robert Colebunders ◽  
Eline Korenromp ◽  
Umberto D'Alessandro

Author(s):  
A. T. Amadi ◽  
I. M. Ezeonu ◽  
O. N. Akoma

Malaria has been a major epidemic that has ravaged millions predominantly in the developing countries of the world with variability in symptoms, causative agents and use of chemotherapy or vector control as preventive measures. Malaria transmission occurs primarily in tropical and subtropical regions in the sub-Saharan Africa, Central and South America. Currently, malaria diagnosis rests mainly on the microscopic detection of parasites in blood samples or rapid diagnostic test (RDT). Preventing drug resistance involves orientation programmes, identification of new treatment modalities, artemisinin (ACT) etc. Treatment failures has been reported for these ACTs leading to an urgency in the need for further novel discoveries and advances in the fight against this menance (antimalarial drug resistance) in developing countries of the world. Understanding the mechanism of action of the antimalarial drugs and most significantly, monitoring the drug resistance to the available antimalarial drugs via regular molecular investigations of resistant markers would definitely aid implementation of effective drug policy.


2020 ◽  
Author(s):  
Gideon Yakusak Benjamin ◽  
Helen Ileigo Inabo ◽  
Hassan Isa Doko Muhammad ◽  
Busayo O Olayinka

Abstract Background Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. The emergence of drug resistance, particularly among P. falciparum strains, has been a major contributor to the global burden of malaria. This research was aimed at detecting genetic markers (pfcrt, pfmdr1, pfdhfr, pfdhps, pfatpase6) associated with antimalarial drug resistance and assessing the distribution of haemoglobin genotypes among malaria patients in of Kaduna State, Nigeria. Methods Three hundred (300) blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. A structured questionnaire was used to obtain relevant data from the study participants. The samples were screened for malaria parasites by microscopy and malaria rapid diagnostic test kit. Deoxyribonucleic acid was extracted from one third of the malaria positive samples, and Polymerase Chain Reaction (PCR) was used for detection of the drug resistance genes. Pfcrt, pfmdr1, pfdhfr, pfdhps and pfatpase6 genes were detected at expected amplicon sizes from the malaria positive samples. The pfatpase6 PCR amplicons were sequenced and a phylogenetic tree was created using MEGA X to determine their relatedness to published sequences. Results Pfcrt (80%) had the highest prevalence, followed by pfdhfr (60%), pfmdr1 (36%) and pfdhps (8%). Pfatpase6 was also detected in 73.3% of the samples. The phylogenetic tree showed that all the pfatpase6 gene sequences (both the ones from this study and those published in NCBI Genbank) had the same origin and were closely related. However, the sequences from NCBI Genbank were from one clade; arising from a common ancestor (monophyletic) thus they were more closely related to themselves, than to the pfatpase6 sequences obtained in this study. Of all the malaria positive participants, those with HbAA (73%) haemoglobin genotype had the highest percentage followed by HbAS (23%), HbAC (3%) and HbSS (1). Conclusion We detected Plasmodium falciparum genes associated with drug resistance to commonly used antimalarials in the study area. Expression of these genes could have serious consequences in the treatment of malaria. The percentage of Plasmodium falciparum malaria was higher among persons with HbAA than those with HbAS, HbAC and HbS.


F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2832 ◽  
Author(s):  
Charlene Wilma Joyce Africa ◽  
Pedro Miguel dos Santos Abrantes

Background:Candidainfections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection. Objectives:This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa. Methods: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinicalCandidaisolates from sub-Saharan African countries using Pubmed and Google Scholar. Results: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences inCandidaspecies prevalence and resistance patterns were identified. Discussion: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected byCandidadrug resistance.  Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the highCandidadrug resistance levels seen to be emerging in sub-Saharan Africa.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sibhatu Biadgilign ◽  
Ayalu Reda ◽  
Haji Kedir

Background. Malaria remains a major cause of mortality and morbidity in the world, and particularly in sub-Saharan Africa.Objectives. The aim of this study was to determine ownership and utilization of ITNs among households with children under five in the previous night.Methods. A community based cross-sectional study was conducted in Gursum district in Eastern Ethiopia. A total of 335 households were surveyed using a pretested structured questionnaire administered though house-to-house interviews.Results. Household ownership for at least one mosquito net and use of nets were 62.4% (95% CI 57.2–67.6%) and 21.5% (95% CI 17.1–25.9%), respectively. Households who received or were told about ITN in the last 6 months were three times more likely to have used it than those who were not (OR 3.25; 95% CI 1.5–7.10). Households whose heads were engaged as a farmer (adjusted OR 0.137; 95% CI: 0.04–0.50) and housewife (OR 0.26; 95% CI: 0.08–0.82) were less likely to use ITN than those of other occupations.Conclusion. The findings indicate low ITN ownership and utilization among the households. Intensive health education and community mobilization effort should be employed to increase the possession and proper utilization of insecticide treated bed nets.


2020 ◽  
Author(s):  
Fang Huang ◽  
He Yan ◽  
Jing-Bo Xue ◽  
Yan-Wen Cui ◽  
Shui-Sen Zhou ◽  
...  

Abstract Background The emergence and spread of multidrug resistance pose a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported since 2017, and China is approaching malaria elimination by 2020. Therefore, it is urgent to monitor antimalarial drug resistance and track the emergence and spread of the imported drug resistant malaria cases in China. Methods Dried blood samples were obtained from P. falciparum infected cases who returned from Africa to China between 2012–2015 prior to antimalarial drug treatment. The known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of the K13 gene were evaluated by nested PCR and sequencing. The GraphPad prism was used to plot the prevalence of each mutation. The chi-squared test and two-sided P value of < 0.05 were used to evaluate differences with statistical significance. Results A total of 731 P. falciparum isolates were successfully genotyped at the pfcrt locus. The wild type haplotype of C72V73M74N75K76 was the most prevalent genotype with the prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype C72V73I74E75T76. Total 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were only observed in codons 86, 184, and 1246. Twelve haplotypes were identified and the prevalence of the wild type variant pfmdr1 N86Y184D1246 was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but D1246Y was rare. The double mutant genotype Y86F184D1246 was common in Africa. A total of 1381 P. falciparum isolates from 33 African countries were sequenced of K13-propeller domain and 1357 were successfully sequenced. The prevalence of K13 mutations was 3.6% and 26 different mutant alleles including 22 nonsynonymous and four synonymous variants (C469C, R471R, G496G, and A627A) were observed. The A578S was the most common haplotype of K13. Three mutation associated with artimisinin resistance (M476I, R539T, and P553L) were observed in three isolates. Conclusion The prevalence of mutant pfcrt and pfmdr1 was low or moderate in P. falciparum isolates imported from Africa to China between 2012–2015. K13-propeller mutations were highly diverse but most mutations were only found in a few isolates. This study provides evidence for the antimalarial drug resistance level of the imported malaria cases from Africa and the efficacy of antimalarial drug policy in China to treat these imported cases.


2021 ◽  
Vol 2 (2) ◽  
pp. 82-90
Author(s):  
A. S. Omar ◽  
B. Son ◽  
F. Wambalaba

In Sub-Saharan Africa, bed nets are mainly aimed at the prevention of the nuisance of mosquito biting rather than against malaria.  The species that are involved in malaria infection are all present in Somalia with the leading one being Plasmodium falciparum that causes about 98% of all infections in the country. This alarming spread of malaria underscores the need to develop interventions that can effectively curb the malaria menace. This study sought to examine the implications of the utilization of long-lasting insecticide-treated bed nets (LLINs) for malaria control and prevention. The population constituted 1,100 pregnant women attending MCH clinics and the two thousand two hundred heads of households, totalling three thousand three hundred. A simple random sampling technique was used to obtain a representative sample of households. In surveying 110 pregnant women attending Maternal Child Health (MCH) clinics and 220 heads of households in the Belet Hawo district in Somalia in 2019, the study found that the majority of households knew the effect of LLINs on preventing malaria. They were also knowledgeable about how to control malaria while facing limited access to LLINs. Furthermore, LLIN usage helped households to raise awareness and knowledge about the effect of LLINs on preventing malaria. This study provided the Somalian government with a better understanding of the causes, control, and prevention of malaria.


2006 ◽  
Vol 50 (11) ◽  
pp. 3734-3739 ◽  
Author(s):  
Jean-Paul Guthmann ◽  
Loretxu Pinoges ◽  
Francesco Checchi ◽  
Simon Cousens ◽  
Suna Balkan ◽  
...  

ABSTRACT The objectives of these analyses were to assess the feasibility of the latest WHO recommendations (28-day follow-up with PCR genotyping) for the assessment of antimalarial drug efficacy in vivo and to examine how different statistical approaches affect results. We used individual-patient data from 13 studies of uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). We assessed the use effectiveness and test performance of PCR genotyping in distinguishing recurrent infections. In analyzing data, we compared (i) the risk of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or excluding (method 2) new infections, (iii) and day 14 versus day 28 results. Of the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. Of the 695 recurrences occurring post-day 14, 650 could be processed and 584 were resolved (PCR use effectiveness, 84%; test performance, 90%). The risks of failure on day 28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close (except in smaller studies) because the numbers of dropouts were minimal, but attrition rates on day 28 were higher with the latter method. Method 2 yielded higher risks of failure than method 1. Extending observation to 28 days produced higher estimated risks of failure for SP and AQ but not for CQ (high failure rates by day 14). Results support the implementation of the current WHO protocol and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows for dropouts) and retaining new infections (which minimizes losses).


2020 ◽  
Author(s):  
Lungwani Muungo

Background. Sub-Saharan countries have experienced centuries of high morbidity and mortality due to malaria. In addition to insecticide-treated mosquito nets and indoor residual spraying, modern antimalarial medicines have been developed to reduce disease prevalence, although the emergence of drug-resistant strains has compromised their efficacy. The purpose of this study was to evaluate the current status of malaria diagnosis and treatment and to monitor the therapeutic efficacy of antimalarial drugs.Materials and Methods. A descriptive cross-sectional survey was conducted from 2011 to 2013 at 10 district hospitals in Zambia designated as malaria sentinel sites as well as at the National Malaria Control Centre. District medical officers at each site completed interview questionnaires.Results. Although basic infrastructure necessary for monitoring antimalarial drug resistance (such as laboratory, dispensary, admission ward, database unit, administration offices, bed space, examination and emergency rooms) was present at all sites, there was a shortage of licensed healthcare personnel. At some sites, antimalarial drugs were prescribed for malaria-like symptoms without diagnostic confirmation by blood smear. There was no regular monitoring of antimalarial drug resistance: only one trial was conducted among all sites in the previous 24 months.Conclusion. A lack of antimalarial drug resistance monitoring might be associated with personnel and funding shortages. Additional financial support would be necessary to avoid the development and spread of drug-resistant malaria in Zambia.


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