Genetic markers associated with antimalarial drug resistance and haemoglobin genotypes among malaria patients in Kaduna State, Nigeria

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.

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Genetic Markers Associated with Antimalarial Drug Resistance and Haemoglobin Genotypes Among Malaria Patients in Kaduna State, Nigeria

10.21203/rs.3.rs-31076/v1 ◽

2020 ◽

Author(s):

Gideon Yakusak Benjamin ◽

Helen Ileigo Inabo ◽

Hassan Isa Doko Muhammad ◽

Busayo O Olayinka

Keyword(s):

Drug Resistance ◽

Phylogenetic Tree ◽

Genetic Markers ◽

Antimalarial Drug ◽

Sub Saharan Africa ◽

Health Concern ◽

Antimalarial Drug Resistance ◽

Test Kit ◽

Sub Saharan ◽

Study Participants

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.

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Detection of Genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria

Nigerian Journal of Parasitology ◽

10.4314/njpar.v42i2.3 ◽

2021 ◽

Vol 42 (2) ◽

pp. 206-213

Author(s):

G.Y. Benjamin ◽

H.I. Inabo ◽

M.H.I. Doko ◽

B.O. Olayinka

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Phylogenetic Tree ◽

Genetic Markers ◽

Cross Sectional Study ◽

Sub Saharan Africa ◽

Health Concern ◽

Cross Sectional ◽

Blood Samples ◽

Test Kit

Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. It is caused by intracellular parasites of the genus Plasmodium. The aim of this study was to detect genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria. The study was a cross-sectional study that lasted from May 2018 to October 2018. Three hundred blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. Structured questionnaire were used to obtain relevant data from study participants. The blood samples were screened for malaria parasites using microscopy and rapid diagnostic test kit. Polymerase Chain Reaction 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 to determine their relatedness. Result showed that 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, and a phylogenetic tree showed relatedness between the pfatpase6 sequences in this study and those deposited in the GenBank. In conclusion, the study detected that Plasmodium falciparum genes were associated with drug resistance to commonly used antimalarials.

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The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance

Malaria Journal ◽

10.1186/1475-2875-7-134 ◽

2008 ◽

Vol 7 (1) ◽

Cited By ~ 24

Author(s):

Jean-Pierre Van geertruyden ◽

Joris Menten ◽

Robert Colebunders ◽

Eline Korenromp ◽

Umberto D'Alessandro

Keyword(s):

Drug Resistance ◽

Antimalarial Drug ◽

Malaria Parasite ◽

Sub Saharan Africa ◽

Antimalarial Drug Resistance ◽

Sub Saharan ◽

The Impact ◽

Hiv 1

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

Frontiers in Genetics ◽

10.3389/fgene.2021.668574 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alexandra T. Roux ◽

Leah Maharaj ◽

Olukunle Oyegoke ◽

Oluwasegun P. Akoniyon ◽

Matthew Adekunle Adeleke ◽

...

Keyword(s):

Drug Resistance ◽

Antimalarial Drug ◽

Indoor Residual Spraying ◽

Sub Saharan Africa ◽

Bed Nets ◽

African Countries ◽

Antimalarial Drug Resistance ◽

Sub Saharan ◽

Insecticide Treated Bed Nets ◽

Emergence Of Resistance

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.

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Antimalarial Drug Resistance: An Existential Burden for the Developing World

Microbiology Research Journal International ◽

10.9734/mrji/2019/v27i430104 ◽

2019 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

A. T. Amadi ◽

I. M. Ezeonu ◽

O. N. Akoma

Keyword(s):

Developing Countries ◽

Drug Resistance ◽

Antimalarial Drug ◽

Malaria Diagnosis ◽

Antimalarial Drugs ◽

Sub Saharan Africa ◽

Treatment Modalities ◽

Antimalarial Drug Resistance ◽

The World ◽

Sub Saharan

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.

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Diagnostic accuracy of molecular methods for detecting markers of antimalarial drug resistance in clinical samples of Plasmodium falciparum: protocol for an update to a systematic review and meta-analysis

Systematic Reviews ◽

10.1186/s13643-018-0891-6 ◽

2018 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Rebekah Burrow ◽

Thomas R. Fanshawe ◽

Georgina S. Humphreys

Keyword(s):

Systematic Review ◽

Drug Resistance ◽

Plasmodium Falciparum ◽

Diagnostic Accuracy ◽

Antimalarial Drug ◽

Meta Analysis ◽

Molecular Methods ◽

Clinical Samples ◽

Antimalarial Drug Resistance

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History and current status of Plasmodium falciparum antimalarial drug resistance in Madagascar

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365540903289670 ◽

2010 ◽

Vol 42 (1) ◽

pp. 22-32 ◽

Cited By ~ 9

Author(s):

Valérie Andriantsoanirina ◽

Didier Ménard ◽

Luciano Tuseo ◽

Rémy Durand

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Antimalarial Drug ◽

Current Status ◽

Antimalarial Drug Resistance

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Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00552-19 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 1

Author(s):

Ruimin Zhou ◽

Chengyun Yang ◽

Suhua Li ◽

Yuling Zhao ◽

Ying Liu ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Antimalarial Drug ◽

Henan Province ◽

Nucleotide Polymorphisms ◽

Combination Therapies ◽

Antimalarial Drug Resistance ◽

Single Nucleotide ◽

Molecular Surveillance ◽

Content Type

ABSTRACT Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.

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