Allelic diversity of merozoite surface protein-1 (MSP 1) and MSP 2 genes, and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia

Abstract

Background Malaria control programme in Indonesia has successfully brought down malaria incidence in many parts of the country, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein genes among the P. falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation. Methods Screening of over 500 malaria cases admitted to the 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and Polymerase Chain Reaction (PCR) amplified for the MSP1 and MSP2 allelic subfamilies. Results Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases classified as severe and 71 as mild malaria. Analysis of MSP 1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of MSP 2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects (carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp2 alleles is slightly higher than MSP 1 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and MSP 1 and MSP 2 alleles revealed that liver function abnormal value was associated with the MSP 2 mixed alleles (p < 0.05; odds ratio = 0.13; CI95%= 0.03–0.53). Malaria severity was associated with the mixed MSP 1 of K1 + RO33 with severe malaria (p < 0.05; odds ratio = 28.50; CI 95%= 1.59-1532.3). Conclusion This study found a strong association between severe malaria in Aceh with subjects carrying the MSP 1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the MSP 2 mixed allelic subfamilies. Further study in different geographic areas is recommended.