Addressing low-density malaria infections in India and other endemic part of the world—the opportune time?

Shifting from high- to low-malaria transmission accompanies a higher proportion of asymptomatic low-density malaria infections (LDMI). Currently, several endemic countries, such as India, are experiencing this shift as it is striving to eliminate malaria. LDMI is a complex concept for which there are several important questions yet unanswered on its natural history, infectiousness, epidemiology, and pathological and clinical impact. India is on the right path to eliminating malaria, but it is facing the LDMI problem. A brief discussion on the concept and definitions of LDMI is beforehand presented. Also, an exhaustive review and critical analysis of the existing literature on LDMI in malaria-endemic areas, including India, are included in this review. Finally, we opine that addressing LDMI in India is ethically and pragmatically achievable, and a pool of sine qua non conditions is required to efficiently and sustainably eliminate malaria.</p

Global polymorphism of <i>Plasmodium falciparum</i> histidine rich proteins 2/3 and impact on malaria rapid diagnostic test detection: a systematic review and meta-analysis

This review presents an overview of field findings on sequence variation of Plasmodium falciparum histidine-rich proteins 2/3 (PfHRP2/3) for which reference types (1–24) have been identified, and its critical impact on PfHRP2-based rapid diagnostic test (RDT) detection. This systematic review and meta-analysis was registered with PROSPERO, CRD42022316027, and conducted as per the PRISMA guidelines, and the methodological quality of studies was assessed. Of the 2184 records identified, 34 studies were included mostly from Africa (47.1%) and Asia (35.3%). The reference PfHRP2 types 1, 2, 3, 6, and 7 are invariably found at proportions ≥ 80–100% in all areas with the exception of The Americas where their proportion is very low. The proteins exhibited high diversity of variants/unknown types, especially for types 1, 2, 4, and 7. Eleven major PfHRP2 epitopes were found at pooled proportion > 90%. The existing models to predict RDT detection are greatly limited by the impact of factors such as low (very low) parasitemia, RDT brand, and PfHRP3 cross-reactivity. PfHRP2 length and presence/number of a given reference repeat type/variant did not seem to impact RDT detection. PfHRP2/3 are highly polymorphic and current findings are insufficient, conflicting and not convincing enough to conclude on the role of PfHRP2/3 sequence polymorphism in PfHRP2-based RDT detection.</p