Table 1.
Summary of the clinical impact and translational aspects of some of the research projects undertaken by the Center
| Research area, reference | Research finding | Clinical impact and/or translational aspect and/or further research suggested |
|---|---|---|
| Epidemiology | ||
| Use of mosquito repellents17 | Mosquito repellants (vaporizers, coils, creams) widely used in India, influenced by socioeconomic status, and not always associated with less malaria | Further clinical testing and evaluation of safety necessary for an evidence-based public health recommendation about how to choose and use repellents |
| Male behavior a risk factor for malaria18 | Repellents used by ∼30% of 234 households in Sundargarh district, Odisha, but insecticide creams not used at all | Promotion of repellent cream use by at-risk groups could be explored in addition to mass screen or treat programs |
| Malaria symptoms and asymptomatic infections16 | Many differences in complaints and symptoms between our sites, and factors associated with asymptomatic Plasmodium infections |
|
| Reactive case detection20 | RCD in areas of low malaria transmission and/or Plasmodium vivax is a labor-intensive strategy, and its benefit is not clear | Further studies are needed to assess how RCD can be optimized or to determine alternatives where interventions are targeted to family members, hotspots, or using serological markers (SeroTAT) |
| Transmission | ||
| Anopheles stephensi breeding habitat29 | Wells and overhead tanks are major breeding sources of the urban vector An. stephensi in Chennai | Overhead tanks as potential vector breeding sites could be targeted for intensified vector intervention measures |
| Zoophilic vectors24 | Shift in vector species toward increased zoophilic behavior in recent years; modeling of regions dominated by zoophilic vectors indicate existing vector control tactics will be insufficient to achieve elimination | Cattle sheds could be targeted by control methods to focus on zoophilic behavior of Anopheles mosquitoes |
| Genome-wide studies | ||
| P. falciparum and P. vivax whole genome sequences38 | P. vivax exhibits twice as much genetic diversity than P. falciparum, suggesting a more stable and older association of this species with humans and suggests an increased capacity for functional variation in the global P. vivax population | P. vivax will be the more difficult species to eliminate. |
| P. vivax population genomics39 | Analysis of 182 clinical isolate genomes from 11 countries identified signals of natural selection suggesting that P. vivax is evolving in response to antimalarial drugs, adapting to regional differences in the human host and mosquito vector | P. vivax has the more variable epidemiology, requiring greater sampling of P. vivax in different endemic regions to capture the standing genetic variation |
| Antibody responses to genome-wide Plasmodium antigens22 | 515 P. vivax and 500 P. falciparum antigens assayed with 353 plasma samples identified most immunogenic antigens of both species and P. falciparum antigens associated with asymptomatic infections | Range of immune responses characterized in different endemic settings in India argues for targeted surveillance approaches tailored to the diverse epidemiology |
| Pathogenesis | ||
| Clinical characterization of CM45 | Posterior reversible encephalopathy syndrome is associated with a reversible nature of the blood–brain barrier and is often associated with nonfatal CM | Evaluation of compounds aimed at reversing vasogenic edema is needed to provide potential new adjunct therapies |
| CM pathology53 | Fatal CM is associated with severe brain swelling in children and with global brain hypoxia in adults | Adjunctive treatment highly likely to differ between the two age groups based on the predominance of cytotoxic edema in adults; focus should be made on decreasing brain hypoxia in adults |
| CM pathogenesis60 | Endothelial protein C receptor-binding PfEMP-1 variants induce endothelial cell swelling and disrupt the blood-brain barrier in CM | Parasite ingress into brain endothelium is a contributing factor to the pathology of human CM |
| CM diagnosis/prognosis46 | hsa-miR-3158-3p represents a promising biomarker candidate for CM prognosis across age groups | hsa-miR-3158-3p may be considered instead of neuroimaging to diagnose and monitor disease progression |
| CM pathogenesis48 | CM-associated brain swelling has common determinants in both African and Indian populations | Adjunct therapies targeting brain swelling in CM patients may be effective in both children and adults, through restoration of normal function of the cytoprotective APC-EPCR signaling pathway |
| Clinical definition of CM52 | Brain changes are frequent in P. falciparum infection, irrespective of the presence of coma | Spectrum of “cerebral” malaria is wider than initially thought; development of neurological sequelae in both uncomplicated malaria and severe noncerebral malaria groups must be evaluated |
CM = cerebral malaria; RCD = reactive cased detection.