Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India.

BACKGROUND: Duffy blood group antigens serve as receptors for Plasmodium vivax invasion into erythrocytes, and they are determined by polymorphisms of the Duffy antigen receptor for chemokines (DARC), also known as Fy glycoprotein (FY). Duffy negativity, i.e., absence of the antigens, protects against P. vivax infection and is rare among non-African populations. However, data on DARC polymorphisms and their impact on Plasmodium infection in India are scarce. METHODS: In a case-control study among 909 malaria patients and 909 healthy community controls in Mangaluru, southwestern India, DARC polymorphisms T-33C (rs2814778), G125A (rs12075), C265T (rs34599082), and G298A (rs13962) were genotyped. Associations of the polymorphisms with the odds of malaria, parasite species and manifestation were assessed. RESULTS: Among patients, vivax malaria (70%) predominated over falciparum malaria (9%) and mixed species infections (21%). DARC T-33C was absent and C265T was rare (1%). FYB carriage (deduced from DARC G125A) was not associated with the risk of malaria per se but it protected against severe falciparum malaria (P = 0.03), and hospitalization (P = 0.006) due to falciparum malaria. Vice versa, carriage of DARC 298A was associated with increased odds of malaria (aOR, 1.46 (1.07-1.99), P = 0.015) and vivax malaria (aOR, 1.60 (1.14-2.22), P = 0.006) and with several reported symptoms and findings of the patients. CONCLUSION: This report from southern India is the first to show an independent effect of the DARC 298A polymorphism on the risk of malaria. Functional studies are required to understand the underlying mechanism. Moreover, FYB carriage appears to protect against severe falciparum malaria in southern India.

Manifestation of malaria in Mangaluru, southern India.

BACKGROUND: Severe and fatal vivax malaria is increasingly reported from India. In Mangaluru, southern India, malaria is focused in urban areas and associated with importation by migrant workers. In Wenlock Hospital, the largest governmental hospital, the clinical, parasitological and biochemical characteristics of malaria patients were assessed. METHODS: During the peak malaria season in 2015 (June to December), outpatients were interviewed and clinically assessed. Malaria was ascertained by microscopy and PCR assays, concentrations of haemoglobin, creatinine and bilirubin, as well as thrombocyte count, were determined, and severe malaria was defined according to WHO criteria. RESULTS: Among 909 malaria patients, the vast majority was male (93%), adult (median, 26 years) and of low socio-economic status. Roughly half of them were migrants from beyond the local Karnataka state, mostly from northern and northeastern states. Vivax malaria (69.6%) predominated over mixed Plasmodium vivax-Plasmodium falciparum infection (21.3%) and falciparum malaria (9.0%). The geometric mean parasite density was 3412/µL. As compared to vivax malaria, patients with falciparum malaria had higher parasite density and more frequently showed impaired general condition, affected consciousness and splenomegaly. Also, they tended to more commonly have anaemia and increased creatinine levels, and to be hospitalized (7.3%). Mixed-species infections largely assumed an interim position. Severe malaria (3.5%) was not associated with parasite species. No fatality occurred. CONCLUSION: In this study, uncomplicated cases of malaria predominated, with P. falciparum causing slightly more intense manifestation. Severe malaria was infrequent and fatalities absent. This contrasts with the reported pattern of manifestation in other parts of India, which requires the analysis of underlying causes.

The Effect of Socioeconomic Factors and Indoor Residual Spraying on Malaria in Mangaluru, India: A Case-Control Study.

India faces 0.5 million malaria cases annually, including half of all Plasmodium vivax malaria cases worldwide. This case-control study assessed socioeconomic determinants of urban malaria in coastal Mangaluru, Karnataka, southwestern India. Between June and December 2015, we recruited 859 malaria patients presenting at the governmental Wenlock Hospital and 2190 asymptomatic community controls. We assessed clinical, parasitological, and socioeconomic data. Among patients, p. vivax mono-infection (70.1%) predominated. Most patients were male (93%), adult (median, 27 years), had no or low-level education (70.3%), and 57.1% were daily labourers or construction workers. In controls (59.3% male; median age, 32 years; no/low-level education, 54.5%; daily labourers/construction workers, 41.3%), 4.1% showed asymptomatic Plasmodium infection. The odds of malaria was reduced among those who had completed 10th school grade (aOR, 0.3; 95% CI, 0.26-0.42), lived in a building with a tiled roof (aOR, 0.71; 95% CI, 0.53-0.95), and reported recent indoor residual spraying (aOR, 0.02; 95% CI, 0.01-0.04). In contrast, migrant status was a risk factor for malaria (aOR, 2.43; 95% CI, 1.60-3.67). Malaria in Mangaluru is influenced by education, housing condition, and migration. Indoor residual spraying greatly contributes to reducing malaria in this community and should be promoted, especially among its marginalised members.

MiRNA-146a Polymorphism Was Not Associated with Malaria in Southern India.

Micro-RNAs (miRNAs) play a crucial role in immune regulation, and a common miRNA-146a polymorphism (rs2910164) increased the odds of falciparum malaria in pregnant African women. Here, we examined whether this association holds true in a different population, that is, 449 mainly male and adult malaria patients and 666 community controls in southwestern India. Plasmodium vivax malaria (67%) predominated over falciparum malaria (11%) and mixed species infections (22%). Overall, 59% of the study participants carried the miRNA-146a polymorphism. However, it was not associated with the odds of malaria, irrespective of parasite species. This underlines the importance of considering the complexities of clinical manifestations of malaria, genetic background, and parasite species when disentangling the role of human genetic variation, including those of miRNAs in malaria.

Malaria Severity in Mangaluru City in the Southwestern Coastal Region of India.

Dakshina Kannada district in the Southwestern region of Karnataka state, India, including Mangaluru city is endemic to malaria. About 80% of malaria infections in Mangaluru and its surrounding areas are caused by Plasmodium vivax and the remainder is due to Plasmodium falciparum. Malaria-associated clinical complications significantly occur in this region. Here, we report the pathological conditions of 41 cases of fatal severe malaria, admitted to the district government hospital in Mangaluru city during January 2013 through December 2016. The results of clinical, hematological, and biochemical analyses showed that most of these severe malaria cases were associated with thrombocytopenia, anemia, metabolic acidosis, acute respiratory distress, and single or multi-organ dysfunction involving liver, kidney, and brain. Of the 41 fatal malaria cases, 24, 10, and seven patients had P. vivax, P. falciparum, and P. vivax and P. falciparum mixed infections, respectively. These data suggest that besides P. falciparum that is known to extensively cause severe and fatal malaria illnesses, P. vivax causes fatal illnesses substantially in this region, an observation that is consistent with recent findings in other regions.

Characterization of Plasmodium vivax pvmdr1 Polymorphisms in Isolates from Mangaluru, India.

India accounts for approximately half of the global Plasmodium vivax cases, but information as to the presence of chloroquine (CQ) resistance is scarce. In an observational study in Mangaluru, south-western India, of 116 vivax malaria patients analyzed, 89.5% (102/114) had cleared parasitemia on days two or three of CQ treatment. Two remaining patients presented on days four and five without parasitemia. One hundred eight isolates of these 116 patients were successfully sequenced for pvmdr1 polymorphisms. Eight non-synonymous polymorphisms but no wild-type isolate were detected. Ten pvmdr1 haplotypes were observed with mutations T958M and F1076L occurring in all isolates, whereas the candidate CQ resistance marker Y976F was present in one isolate only. Pvmdr1 polymorphisms were not associated with early parasite clearance. The high proportion of early parasite clearance and the virtual absence of pvmdr1 Y976F and of sextuple pvmdr1 mutants suggest that CQ in the study area is still sufficiently effective. However, the abundance of pvmdr1 mutations in the local parasite population warrants monitoring.

Molecular Evidence for Plasmodium falciparum Resistance to Sulfadoxine-Pyrimethamine but Absence of K13 Mutations in Mangaluru, Southwestern India.

In most of India, sulfadoxine-pyrimethamine (SP) plus artesunate serves as first-line treatment for uncomplicated falciparum malaria. In 112 clinical Plasmodium falciparum isolates from Mangaluru, southwestern India, we sequenced molecular markers associated with resistance to SP, lumefantrine, and artemisinin (pfdhfr, pfdhps, pfmdr1, and K13). The pfdhfr double mutation 59R-108N combined with the dhps 437G mutation occurred in 39.3% and the pfdhfr double mutation plus the pfdhps double mutation 437G-540E in additional 24.1%. As for pfmdr1, the allele combination N86-184F-D1246 dominated (98.2%). K13 variants were absent. No evidence for artemisinin resistance was seen. However, the antifolate resistance alleles compromise the current first-line antimalarial sulfadoxine-pyrimethamine plus artesunate, which may facilitate the emergence of artemisinin resistance. Artemether-lumefantrine, introduced in northeastern parts of the country, in the study area faces the predominant pfmdr1 NFD genotype, known to impair lumefantrine efficacy. Further monitoring of resistance alleles and treatment trials on alternative artemisinin-based combination therapies are required.