K13-Propeller Polymorphisms in Plasmodium falciparum Isolates from Patients in Mayotte in 2013 and 2014.

Plasmodium falciparum isolates were collected from 29 malaria patients treated with artemether-lumefantrine in Mayotte in 2013 and 2014. Twenty-four cases (83%) consisted of imported malaria. Seventeen percent of the isolates presented mutations in one of the six K13-propeller blades (N490H, F495L, N554H/K, and E596G). A total of 23.8% of the isolates from the Union of Comoros showed K13-propeller polymorphisms. Three of the 18 isolates (16.7%) from Grande Comore showed polymorphisms (N490H, N554K, and E596G).

Major decrease in malaria transmission on Mayotte Island.

BACKGROUND: Plasmodium falciparum is responsible for most malaria cases on Mayotte Island, in the Comorian Archipelago. Malaria is endemic and a major public health problem in the archipelago with an intense, stable and permanent transmission. This study reports results of 8 years of malaria surveillance from 2007 to 2014 after the strengthening of malaria control activities in Mayotte and the neighbouring islands. METHODS: Surveillance was based on physicians' reports of malaria cases between January 2007 and December 2014. Malaria cases were confirmed by at least a positive rapid diagnostic test and/or demonstration of Plasmodium sp. in a blood smear. The date, and the patients' age, sex, address, presentation of symptoms, biology, treatment and recent history of travel were collected by verbal questioning during consultation and/or hospitalization. Monthly rainfall data were also compiled during the study period. RESULTS: From 2007 to 2014, 2073 cases were reported on Mayotte Island: 977 imported cases, 807 autochthonous cases and 289 cases of unknown origin. The total malaria annual parasite incidence lowered from 3.0 in 2007 to 0.07 per 1,000 inhabitants in 2014 as the autochthonous malaria incidence decreased from 1.6 to 0.004 per 1,000 inhabitants in the same period and in all age groups. Most of the imported cases came from Comoros (94 %). Severe forms represented approximately 11 % of cases, and only two deaths have been recorded among the imported cases. Approximately 19 % of cases were hospitalized (3 % in an intensive care unit). There is clearly a decrease in malaria transmission in Mayotte since 2007 and the goal of elimination seems more achievable than ever. In 2011, Mayotte entered the elimination phase when P. falciparum API passed under 1 case per 1,000 people at risk. CONCLUSIONS: The combination of vector control measures, active surveillance and case management, including effective treatment with artemisinin-based combination therapy, has been essential to achieve a present status of low and decreasing malaria transmission on the island. Mayotte has entered the elimination phase, but some goals remain to be accomplished before a programme re-orientation toward malaria elimination is contemplated. Moreover, a regional management policy is crucial because this would allow control measures to be targeted and based on a regional surveillance-response system rather than isolated.

[Mayotte, a malaria-free island at last?] / Mayotte, une île enfin exempte de paludisme?

Mayotte is a French overseas department and one of the 4 islands of the Comoros archipelago in the Indian Ocean, located between Madagascar and the eastern coast of Africa. Malaria, mainly by Plasmodium falciparum, is endemic to the archipelago and remained a major public health problem until recent years. To control and then eliminate the disease, major strategies have been established in Mayotte since 2001. Preventive measures, diagnostic testing, treatment and disease surveillance were introduced or improved.From 2002 to 2021, 4819 autochthonous cases were reported in Mayotte where the annual incidence decreased from 10.3 per 1,000 population in 2002 (1649 cases) to less than 0.01 per 1,000 population in 2020 (2 cases). The incidence has been below 1 per 1,000 population since 2009. In 2013, WHO classified Mayotte as a territory in malaria elimination phase. In 2021, no locally acquired malaria cases were reported on the island. During this period 2002-2021, 1898 imported cases were observed. They mainly came from the Union of Comoros (85.8%), Madagascar (8.6%) and sub-Saharan Africa (5,6%). Since 2017, the annual number of locally acquired cases was less than 10 and decreased steadily (9 cases in 2017, 5 in 2018, 4 in 2019 and 2 in 2020). The distribution of these rare locally acquired cases both in time and space suggests that they were introduced and not indigenous cases. A study of the genotypic profile of the plasmodial strains of these cases observed from 2017 to 2020 (17 cases analysed out of 20 diagnosed) confirms that these were certainly introduced cases related to imported cases from the neighboring Comoros.Malaria indigenous transmission seems to be eliminated in Mayotte, but the island remains under threat of reintroduction via cases imported from neighbouring countries. It is time to develop a local plan to prevent reintroduction and to implement a proactive policy of regional cooperation in the fight against malaria.

Adaptive differentiation of Plasmodium falciparum populations inferred from single-nucleotide polymorphisms (SNPs) conferring drug resistance and from neutral SNPs.

BACKGROUND: Theoretical and experimental data support the geographic differentiation strategy as a valuable tool for detecting loci under selection. In the context of Plasmodium falciparum malaria, few populations have been studied, with limited genomic coverage. METHODS: We examined geographic differentiation in P. falciparum populations on the basis of 12 single-nucleotide polymorphisms (SNPs) in 4 genes encoding drug resistance determinants, 5 SNPs in 2 genes encoding antigens, and a set of 17 putatively neutral SNPs dispersed on 13 chromosomes. We sampled 326 parasite isolates representing 7 P. falciparum populations from regions with varied levels of malaria transmission (Gabon, Kenya, Madagascar, Mali, Mayotte, Haiti, and the Philippines). RESULTS: Frequencies of drug resistance alleles varied considerably among populations (mean F(ST), 0.52). In contrast, allele frequencies varied significantly less for antigenic and neutral SNPs (mean F(ST), 0.16 and 0.24, respectively). This contrasting pattern was more pronounced when only the African populations were considered. Signature of selection was detected for most of the resistant SNPs but not for the antigenic SNPs. CONCLUSION: These data further validate the utility of geographic differentiation for identifying loci under strong positive selection, such as drug resistance loci. This study also provides frequencies of molecular makers of resistance in some overlooked populations.

Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago.

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.

[Malaria diagnosis and treatment in a rural Health Centre in Mayotte (Comoro archipelago, 2002)]. / Le diagnostic et le traitement des accès palustres dans un dispensaire rural à Mayotte (Archipel des Comores) en 2002.

With a marked increase in both morbidity and mortality, as well as a high level of resistance to chloroquine (CQ), malaria is once again a major public health problem in Mayotte, a French overseas territory in the Comoro archipelago. The object of this study is to assess the contribution in the field of two new antimalarial fight steps taken in 2001-2002: The use of the rapid diagnostic test (RDT) for malaria OptiMAL in the rural health centres and the drop of the CQ alone for the simultaneous administration of CQ and sulfadoxine-pyrimethamine (SP) as the first-line treatment for uncomplicated malaria. All 581 suspected malaria attacks, diagnosed by RDT during the year 2002 in a rural health centre of the island, were registered. The good positive predictive value of the RDT used (97.2%) calculated during the study has permitted an important reduction of the rate of wrongly administer antimalarial treatment. Before RDT was used, through lack of emergency microscopic diagnosis, the antimalarial treatment was presumptive in the isolated health centres and that rate was superior to 90%. It is now below 3%. Before the introduction of the new protocol, in the middle of the year 2002, the rate of therapeutic failures with CQ used alone was 40.2% (33/82). With the simultaneous administration of CQ and SP as a first-line treatment, this rate fell down to 1.8% (6/337). For the time being, this new treatment policy is acceptable in Mayotte. But the experience of the countries who have adopted this therapeutic policy shows that the effectiveness of the association CQ-SP is likely to be temporary. It is necessary to set up a "durable long-term" therapy strategy in Mayotte as soon as possible by adopting as first-line treatment for uncomplicated malaria a combination therapy according to the recommendations of the World Health Organization. It could be the artemether-lumefantrine combination which has already been the subject of an efficacy survey in the island.