Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia
Abstract Background In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less th...
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ftdoajarticles:oai:doaj.org/article:b8dbff646e33409da428d530df1cdc93 2023-05-15T15:15:36+02:00 Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia Rouse Petrica Sikalima Jay Chishimba Sandra Mkulama Mtawa AP Thuma Philip E Mharakurwa Sungano 2008-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-7-87 https://doaj.org/article/b8dbff646e33409da428d530df1cdc93 EN eng BMC http://www.malariajournal.com/content/7/1/87 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-7-87 1475-2875 https://doaj.org/article/b8dbff646e33409da428d530df1cdc93 Malaria Journal, Vol 7, Iss 1, p 87 (2008) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2008 ftdoajarticles https://doi.org/10.1186/1475-2875-7-87 2022-12-30T21:41:22Z Abstract Background In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs. The current study assessed the status of Plasmodium falciparum point mutations associated with antifolate drug resistance in the area around Macha. Methods A representative sample of 2,780 residents from the vicinity of Macha was screened for malaria by microscopy. At the same time, blood was collected onto filter paper and dried for subsequent P. falciparum DNA analysis. From 188 (6.8%) individuals that were thick film-positive, a simple random sub-set of 95 P. falciparum infections were genotyped for DHFR and DHPS antifolate resistance mutations, using nested PCR and allele-specific restriction enzyme digestion. Results Plasmodium falciparum field samples exhibited a high prevalence of antifolate resistance mutations, including the DHFR triple (Asn-108 + Arg-59 + Ile-51) mutant (41.3%) and DHPS double (Gly-437 + Glu-540) mutant (16%). The quintuple (DHFR triple + DHPS double) mutant was found in 4 (6.5%) of the samples. Levels of mutated parasites showed a dramatic escalation, relative to previous surveys since 1988. However, neither of the Val-16 and Thr-108 mutations, which jointly confer resistance to cycloguanil, was detectable among the human infections. The Leu-164 mutation, associated with high grade resistance to both pyrimethamine and cycloguanil, as a multiple mutant with Asn-108, Arg-59 and (or) Ile-51, was also absent. Conclusion This study points to escalating levels of P. falciparum antifolate resistance in the vicinity of Macha. Continued monitoring is recommended to ensure timely policy revisions before widespread resistance exacts ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Macha ENVELOPE(127.166,127.166,73.003,73.003) Malaria Journal 7 1 87 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Rouse Petrica Sikalima Jay Chishimba Sandra Mkulama Mtawa AP Thuma Philip E Mharakurwa Sungano Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs. The current study assessed the status of Plasmodium falciparum point mutations associated with antifolate drug resistance in the area around Macha. Methods A representative sample of 2,780 residents from the vicinity of Macha was screened for malaria by microscopy. At the same time, blood was collected onto filter paper and dried for subsequent P. falciparum DNA analysis. From 188 (6.8%) individuals that were thick film-positive, a simple random sub-set of 95 P. falciparum infections were genotyped for DHFR and DHPS antifolate resistance mutations, using nested PCR and allele-specific restriction enzyme digestion. Results Plasmodium falciparum field samples exhibited a high prevalence of antifolate resistance mutations, including the DHFR triple (Asn-108 + Arg-59 + Ile-51) mutant (41.3%) and DHPS double (Gly-437 + Glu-540) mutant (16%). The quintuple (DHFR triple + DHPS double) mutant was found in 4 (6.5%) of the samples. Levels of mutated parasites showed a dramatic escalation, relative to previous surveys since 1988. However, neither of the Val-16 and Thr-108 mutations, which jointly confer resistance to cycloguanil, was detectable among the human infections. The Leu-164 mutation, associated with high grade resistance to both pyrimethamine and cycloguanil, as a multiple mutant with Asn-108, Arg-59 and (or) Ile-51, was also absent. Conclusion This study points to escalating levels of P. falciparum antifolate resistance in the vicinity of Macha. Continued monitoring is recommended to ensure timely policy revisions before widespread resistance exacts ... |
format |
Article in Journal/Newspaper |
author |
Rouse Petrica Sikalima Jay Chishimba Sandra Mkulama Mtawa AP Thuma Philip E Mharakurwa Sungano |
author_facet |
Rouse Petrica Sikalima Jay Chishimba Sandra Mkulama Mtawa AP Thuma Philip E Mharakurwa Sungano |
author_sort |
Rouse Petrica |
title |
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
title_short |
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
title_full |
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
title_fullStr |
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
title_full_unstemmed |
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia |
title_sort |
escalating plasmodium falciparum antifolate drug resistance mutations in macha, rural zambia |
publisher |
BMC |
publishDate |
2008 |
url |
https://doi.org/10.1186/1475-2875-7-87 https://doaj.org/article/b8dbff646e33409da428d530df1cdc93 |
long_lat |
ENVELOPE(127.166,127.166,73.003,73.003) |
geographic |
Arctic Macha |
geographic_facet |
Arctic Macha |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 7, Iss 1, p 87 (2008) |
op_relation |
http://www.malariajournal.com/content/7/1/87 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-7-87 1475-2875 https://doaj.org/article/b8dbff646e33409da428d530df1cdc93 |
op_doi |
https://doi.org/10.1186/1475-2875-7-87 |
container_title |
Malaria Journal |
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7 |
container_issue |
1 |
container_start_page |
87 |
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1766345970572853248 |