News — A recent genomic analysis conducted by the Barcelona Institute for Global Health (ISGlobal) and the Manhiça Health Research Center (CISM) confirms the continued effectiveness of malaria treatment and prevention drugs in Mozambique. The study, published in Communications Biology, also unveils regional variations within the parasite.
In the battle against malaria, the utilization of antimalarial drugs plays a crucial role in both prevention and treatment. Unfortunately, the malaria-causing parasite known as P. falciparum has developed resistance to numerous antimalarial drugs. One notable example is the emergence of resistance to artemisinin, which is the primary treatment for P. falciparum malaria. This resistance is characterized by specific mutations in the parasite gene pfkelch13.
Additionally, resistance to sulfadoxine-pyrimethamine (SP), commonly used to prevent malaria in pregnant women and infants, is primarily associated with three mutations in the pfdhps gene and two mutations in the pfdhfr gene. These mutations contribute to reduced effectiveness of SP in combating the malaria parasite.
Keeping a close watch on the presence and dissemination of these drug resistance markers is of paramount importance in guiding malaria control programs and preserving the efficacy of the utilized drugs. Alfredo Mayor, a researcher at ISGlobal and CISM, emphasizes the significance of this endeavor by stating, "In Mozambique, various studies have identified drug resistance markers, but their geographical distribution remained largely unknown." This aspect is particularly relevant due to the heterogeneous nature of malaria transmission in Mozambique, characterized by a substantial disease burden in the north and significantly lower transmission rates in the south.
Mayor and his team conducted a comprehensive study in which they investigated the geographic dispersion of antimalarial drug resistance markers in Mozambique over a span of multiple years. To accomplish this, they employed state-of-the-art techniques to sequence a total of 2,251 samples of P. falciparum. These samples were collected from different regions of south, central, and north Mozambique between the years 2015 and 2018. By analyzing the genetic material of the parasite, the researchers aimed to gain insights into the distribution patterns of drug resistance markers across the country.
A north-south divide
Through genomic analysis, it was determined that there is no indication of genetic markers associated with artemisinin resistance. Moreover, the prevalence of resistance markers for chloroquine or piperaquine (used in combination with artemisinin) was found to be very low. However, a contrasting finding revealed a significantly high frequency of resistance markers for SP (sulfadoxine-pyrimethamine): quintuple mutants, characterized by three mutations in pfdhps and two mutations in pfdhfr, increased from 80% in 2015 to 89% in 2018. This increase was observed from the northern to the southern regions of the country, indicating a spatial gradient. Additionally, this geographical variation was accompanied by a decrease in the number of genetically distinct parasites infecting an individual, suggesting lower malaria transmission intensity in the southern areas.
In addition, another mutation associated with SP resistance was exclusively identified in the northern region of the country, specifically in Cabo Delgado. This mutation had a frequency of 17% and was never observed in conjunction with the two mutations in the pfdhr gene. Simone Boene, a co-first author of the study along with Clemente da Silva, suggests that the observed regional variation in parasite mutations may be attributed to various factors, such as geographical distance and variations in the utilization and effectiveness of antimalarial interventions.
Public health implications
The findings from this study hold significant implications for public health in Mozambique. Firstly, the effectiveness of artemisinin in treating P. falciparum malaria remains intact, which is encouraging for malaria treatment efforts. Secondly, the use of piperaquine in artemisinin combination therapies (ACT) can still be employed successfully. Thirdly, despite the high prevalence of quintuple mutants, there is no evidence suggesting a reduced effectiveness of SP as a chemopreventive measure. Moreover, a mutation in pfdhps that is known to diminish the drug's efficacy in infants and pregnant women was detected in only 0.2% of the samples analyzed, supporting the continued use of SP for malaria prevention in pregnant women through IPTp (Intermittent Preventive Treatment in pregnancy).
However, the authors caution that close monitoring of these resistance markers is crucial due to the rapid emergence of artemisinin and piperaquine resistance observed in Southeast Asia. The escalating resistance situation in that region serves as a reminder of the importance of vigilance and proactive measures to prevent the spread of resistance in Mozambique.
Da Silva emphasizes that these findings serve as essential baseline data for studying the evolutionary patterns of P. falciparum parasites in response to the evolving national malaria treatment guidelines. To effectively monitor the emergence and dissemination of drug-resistant parasites, the authors underscore the importance of integrating molecular surveillance systems with drug efficacy studies. By combining these approaches, researchers can gain valuable insights into the dynamics of drug resistance and make informed decisions regarding malaria treatment and control strategies. Continuous monitoring and research in this area are vital for staying ahead of the potential challenges posed by drug-resistant parasites.
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