Despite consistent public health efforts for over half a century for mitigation of its spread, malaria—caused by five species of plasmodium—remains a widely prevalent disease affecting 84 countries as of today (1). Newer challenges continue to plague malaria control programs, with a recent example being disruption of services due to the COVID-19 pandemic. An undeniable rise in the incidence, morbidity, and mortality attributable to Plasmodium vivax in the last decade has led to a renewed interest in its pathogenicity and an acute need of realistic estimates of its global disease burden (2, 3).
P. vivax is the most geographically spread of malarial parasites. Although the World Health Organization (WHO) captures a decline in case proportions of P. vivax (1), an increasing body of evidence emphasizes the not-so-benign nature of vivax malaria. P. vivax has broken the evolutionary barrier and is increasingly reported from Duffy blood group-negative sub-Saharan Africa (4, 5). The WHO's global technical strategy for malaria operates under a highly ambitious target of eliminating malaria from 35 countries by 2030 and reducing incidence and mortality rates worldwide by 90%. P. vivax has been recognized as a major epidemiological challenge to achieving these targets, chiefly due to key differences in parasite and vector biology (3) (Table 1).
Challenges to public health measures for control of vivax malaria
Likewise, host factors contribute to enhanced pathogenicity in vivax malaria. Pronounced inflammatory response despite low parasitemia (6); higher cytokine production (interferon-γ/interleukin-10 ratio and C-reactive protein) (7); endothelial stimulation (8); capillary sequestration (8); and persistent hepatic, splenic, and bone marrow reservoir formation lead to severe disease with multi-organ dysfunction not unlike that with Plasmodium falciparum. P. vivax disproportionately affects other high-risk groups, such as pregnant women and children, in areas of high transmission (3, 9–11).
Cytoadherence leading to formation of rosettes and clumps is implicated in impaired microcirculation and organ damage in vivax malaria. Coupled with hypovolemia and shock, this contributes to acute kidney injury (AKI) (Figure 1). Malarial kidney biopsies show acute tubular necrosis, acute cortical necrosis, thrombotic microangiopathy, glomerulonephritis, or tubulo-interstitial nephritis (12–17). Postinfectious glomerulonephritis (18) and crescentic glomerulonephritis (19) have also been reported. Recent studies have demonstrated the presence of P. vivax DNA in kidney biopsies (14). Sequestrated parasites in donor organs can lead to symptomatic disease in transplant recipients (20–23). Curiously, one of the early reports describes synchronous, high-grade fever in two kidney transplant recipients attributed to P. vivax acquired from the same deceased donor (24).
Pathophysiology of renal involvement in vivax malaria
Citation: Kidney News 15, 3
Multiple large case series of malarial AKI from the Indian subcontinent report the proportion of P. vivax as 15.2% (25), 20.4% (26), 41.79% (27), and 54.4% (28). Renal replacement therapy was required in 33.3%–76.6% of these cases. Mortality was observed to be 15%–20%. Predictive factors for mortality varied across studies; however, most pointed toward advanced multi-organ dysfunction reflecting severe malaria. Prognosis of vivax malaria-associated kidney injury is favorable. Approximately two-thirds of cases show complete recovery within 2–3 weeks. Appropriate anti-malarial drugs, anti-hypnozoite therapy (Primaquine), non-dialytic supportive care and timely initiation of renal replacement therapy for AKI (most effectively, hemodialysis), and treating multi-organ dysfunction are the cornerstones of management.
The conventional perspective of human malaria needs to evolve to accommodate the obscure disease burden and changing epidemiology of vivax malaria. P. vivax has proven to be a tenacious parasite. Newer research directed towards detection, accurate estimation of morbidity and mortality, preventive, and curative therapy is imperative for further progress.
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