ABSTRACT
BACKGROUND: In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains. OBJECTIVES: To assess the prevalence of triple-resistant parasites after artesunate/mefloquine implementation countrywide in Cambodia and to characterize their phenotype. METHODS: For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses. RESULTS: Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination. CONCLUSIONS: The use of artesunate/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs.
Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Quinolines , Humans , Mefloquine/pharmacology , Mefloquine/therapeutic use , Plasmodium falciparum/genetics , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artesunate , Cambodia/epidemiology , Prevalence , Artemisinins/pharmacology , Artemisinins/therapeutic use , Quinolines/pharmacology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Drug Resistance/geneticsABSTRACT
BACKGROUND: Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. OBJECTIVES: This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. PATIENTS AND METHODS: Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. RESULTS: The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. CONCLUSIONS: Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.
Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Malaria , Quinolines , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Cameroon , Humans , Malaria/drug therapy , Malaria, Falciparum/drug therapy , Plasmodium falciparum/genetics , Quinolines/therapeutic useABSTRACT
BACKGROUND: Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown. METHODS: In two forested regions of Cambodia, forest-goers were trained to become forest malaria workers (FMWs). In one region, FMWs performed mass screening and treatment, focal screening and treatment, and passive case detection inside the forest. In the other region, FMWs played an observational role for the first year, to inform the choice of intervention for the second year. In both forests, FMWs collected blood samples and questionnaire data from all forest-goers they encountered. Mosquito collections were performed in each forest. RESULTS: Malaria prevalence by PCR was high in the forest, with 2.3-5.0% positive for P. falciparum and 14.6-25.0% positive for Plasmodium vivax among forest-goers in each study site. In vectors, malaria prevalence ranged from 2.1% to 9.6%, but no P. falciparum was observed. Results showed poor performance of mass screening and treatment, with sensitivity of rapid diagnostic tests equal to 9.1% (95% CI 1.1%, 29.2%) for P. falciparum and 4.4% (95% CI 1.6%, 9.2%) for P. vivax. Malaria infections were observed in all demographics and throughout the studied forests, with no clear risk factors emerging. CONCLUSIONS: Malaria prevalence remains high among Cambodian forest-goers, but performance of rapid diagnostic tests is poor. More adapted strategies to this population, such as intermittent preventive treatment of forest goers, should be considered.
Subject(s)
Culicidae/parasitology , Disease Eradication/statistics & numerical data , Forests , Malaria/prevention & control , Mosquito Vectors/parasitology , Animals , Asian People/statistics & numerical data , Cambodia/epidemiology , Disease Eradication/methods , Female , Humans , Malaria/blood , Malaria/diagnosis , Malaria/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/prevention & control , Malaria, Vivax/epidemiology , Malaria, Vivax/prevention & control , Mass Screening/statistics & numerical data , Operations Research , Prevalence , Risk FactorsABSTRACT
The estimated mortality rates for breast and cervical cancer in Cambodia are high, perhaps because the Cambodian population lacks information about their detection and prevention. This cross-sectional study assessed the distribution of cervical cancers among and the behavioural and clinical characteristics of Cambodian women. It comprised 1039 Cambodian women who were interviewed between August 2013 and January 2016; the interviews were conducted in person using structured questionnaires. Among the participants, 801 (77.2%) and 709 (68.3%) had heard of cervical cancer and cervical cancer detection tests, respectively. However, 830 (80.2%) had never undergone a Pap smear, and 633 (60.9%) had never heard of breast self-examination. Despite the high mortality rates for breast and cervical cancer in Cambodia, only a small percentage of the participants had risk factors (e.g. smoking, alcohol consumption) for female cancers. A nationwide survey of the knowledge, attitudes and practices related to female cancers is recommended.Impact StatementWhat is already known on this subject? The estimated incidence and mortality rates of breast and cervical cancers in Cambodia are high. How much Cambodian women know about these cancers and whether they are receptive to cancer screening are questions requiring further study.What do the results of this study add? To our knowledge, this is the first study to describe the female cancer-related behavioural and clinical characteristics of Cambodian women. We show that rural Cambodian women are mostly unaware of breast and cervical cancer screening and that only a small percentage had risk factors for these cancers, despite the high incidence of these cancers in Cambodia.What are the implications of these findings for clinical practice and/or further research? Our findings potentially aid the design of programmes that increase awareness of breast and cervical cancers in Cambodia. Such programmes would be expected to reduce the incidence and mortality rates of these cancers in this country. Nationwide screening programmes for female cancers should be implemented in Cambodia.
Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer/psychology , Health Knowledge, Attitudes, Practice , Uterine Cervical Neoplasms/diagnosis , Adult , Breast Neoplasms/mortality , Breast Neoplasms/psychology , Cambodia/epidemiology , Cross-Sectional Studies , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Female , Health Behavior , Humans , Middle Aged , Risk Assessment , Risk Factors , Rural Population/statistics & numerical data , Surveys and Questionnaires , Urban Population/statistics & numerical data , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/psychologyABSTRACT
Background: Cambodia targets P. falciparum malaria elimination by 2023 and all human malaria species by 2025, aligning with WHO's Mekong Malaria Elimination program. The Intermittent Preventive Treatment for Forest Goers (IPTf) project aimed at forest-specific malaria elimination. The study aims to pinpoint the main factors driving malaria transmission in Cambodian forests and evaluate the initial implementation and effectiveness of IPTf in accelerating the elimination of malaria by treating and preventing infections among at-risk populations in these areas. Methods: From March 11, 2019, to January 30, 2021, a malaria intervention program took place in isolated forests in Northeast Cambodia. The first phase focused on observing forest goers (FGs) within the forests, documenting their malaria risk. In the second phase, a monthly artesunate-mefloquine IPTf was implemented by trained forest malaria workers who were former FGs conducting interviews, blood collection, and IPTf administration. Findings: Throughout the two-year period, 2198 FGs were involved in 3579 interviews, with 284 in both the observation and intervention phases. Following IPTf implementation, PCR-confirmed malaria prevalence significantly decreased from 2.9% to 0.5% for P. falciparum and from 21.0% to 4.7% for P. vivax. Among the 284 participants tracked through both phases, malaria prevalence fell from 2.5% to 0.3% for P. falciparum and from 22.5% to 3.7% for P. vivax. The intervention phase demonstrated a rapid decline in P. falciparum prevalence among mobile and previously inaccessible populations, while also revealing a higher P. falciparum infection risk associated with activities inaccurately labelled as farming, underscoring the need for customized interventions. Interpretation: The successful implementation of IPTf in Cambodia's remote forests has markedly decreased malaria prevalence among high-risk groups. Cambodia's National Malaria Program has acknowledged this strategy as essential for malaria elimination intervention, endorsing forest-specific approaches to meet the 2025 goal of eradicating all human malaria species in Cambodia. Funding: The study received funding from the French 5% Initiative (Initiative Canal 2-17SANIN205).