Epidemiology of malaria in the provinces of Sarangani, South Cotabato and TawiTawi in Mindanao, The Philippines

The Philippines is targeting malaria elimination by 2020. To reach this goal, it is important to locate all residual foci of malaria and where possible, aggressively diagnose and treat every malaria infection. In low endemic provinces malaria transmission becomes focal in hard-to-reach areas where asymptomatic people do not actively seek treatment and thus, continue to perpetuate transmission. This study aimed (a) to estimate prevalence of Plasmodium species in three malaria-endemic provinces in Mindanao, (b) to measure malaria transmission intensity in these provinces using antibody markers of exposure to P. falciparum and P. vivax AMA-1 and MSP-119 antigens, (c) to determine polymorphisms in pfcrt, pfmdr1 and pvmdr1 genes, and (d) to discuss implications of these findings to malaria elimination in Mindanao. Cross-sectional surveys were conducted to a total of 2,628 consenting participants across all ages in the provinces of Sarangani, South Cotabato and Tawi-Tawi from 2010 to 2013. The RDT FalciVax™ was used for field diagnosis of malaria in Sarangani Province and South Cotabato Province for P. falciparum and P. vivax infection while microscopy was used in Tawi-Tawi Province for field diagnosis of malaria. Finger-prick blood spots on filter paper were collected from participants for PCR diagnosis, genotyping of pfcrt, pfmdr1 and pvmdr1 genes, and screening antibodies to P. falciparum and P. vivax AMA-1 and MSP-119 antigens using indirect ELISA. Blood spots were also collected from patients presenting with malaria symptoms from selected municipalities of Sarangani Province and South Cotabato Province as a pilot survey. Overall malaria prevalence by PCR was 3.7% in Sarangani Province, 10% in South Cotabato Province and 4.2% in Tawi-Tawi Province. P. falciparum prevalence by PCR was higher than P. vivax prevalence in Sarangani Province and Tawi-Tawi Province but the opposite was found in South Cotabato Province. There was one imported case of P. malariae in South Cotabato and there were no P. knowlesi and P. ovale infections found in the three provinces surveyed. There were disagreements in diagnosing P. falciparum and P. vivax using antigen detection, microscopy and PCR and these were attributed to sampling low parasite-density infections from small volume of peripheral blood spotted on filter paper. The pfcrt codons 72-76 haplotypes CVMNK (27.4%), CVIET (59.7%) and SVMNT (9.7%) were described in 62 P. falciparum isolates from Mindanao. The pfcrt mutant A144T and L160Y alleles were not found among P. falciparum isolates with pfcrt K76T mutant allele but lacked the pfcrt A220S mutation. The pfmdr1 86N- 184F-1034S-1042N-1246D haplotype, which was repeatedly associated with higher parasite survival following artemether-lumefantrine treatment, was found in seven P. falciparum isolates from Mindanao. Genotyped P. vivax isolates from Mindanao have the wild type pvmdr1 91N allele, which corresponded to pfmdr1 codon 86. The pvmdr1 Y976F mutant allele, which has been reported in chloroquine-resistant P. vivax in other countries, was found in 55.6% (5/9) P. vivax isolates successfully genotyped in this codon while the pvmdr1 1076L wild-type allele was found in three P. vivax isolates successfully genotyped in this codon. Combined seroprevalence to P. falciparum and P. vivax AMA-1 and MSP-119 antigens suggested that exposure to P. falciparum was higher than exposure to P. vivax in Sarangani Province and Tawi-Tawi Province. Overall seroprevalence to P. falciparum and P. vivax was 18.9% and 14.6% in Sarangani Province respectively. In Tawi-Tawi Province the overall seroprevalence to P. falciparum and P. vivax was 18.2% and 12.9% respectively. The opposite was observed in South Cotabato Province where overall seroprevalence to P. falciparum (3.4%) was lower than the overall seroprevalence to P. vivax. The seroconversion rates (λ) for P. falciparum and P. vivax malaria were estimated using simple reversible catalytic models. In Sarangani Province the SCR for P. falciparum (0.014, 95%CI 0.010-0.020) was lower than SCR for P. vivax (0.019, 95% CI 0.010-0.036). A model allowing two forces of infection was used to estimate SCR for P. falciparum in Tawi-Tawi. Results suggested that there was a change in P. falciparum transmission in Tawi-Tawi Province approximately 25 years before the survey was conducted. The estimated SCR for P. falciparum was 0.041 (95% CI 0.017-0.098) in Tawi-Tawi Province before 1987. The model suggested that SCR was reduced to 0.007 (95% CI 0.005-0.009) after 1987 to the time of survey. In South Cotabato the SCR for P. falciparum was very low (0.004, 95% CI 0.001-0.016). There was no SCR estimated for P. vivax in South Cotabato because seropositivity was equally distributed across age groups. Findings in this study were held back by sample size and low-density parasite infections in small number of infected humans. Nevertheless, this provided important baseline data for malaria epidemiology in Mindanao.