Renal detection of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in malaria associated acute kidney injury: a retrospective case–control study

Abstract

Objective: Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues. Results: We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono-and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

Association of Dengue Virus and Leptospira Co-Infections with Malaria Severity

“…P. knowlesi, which was previously believed to be localized to Southeast Asia, has now been reported from various parts of the world as single case reports of travelers' infections from areas including Oceania, Europe, and the Middle East (39)(40)(41). From India, P. knowlesi infection has been reported from the Andaman and Nicobar Islands in the context of drug resistance and in a recent study by our group in the context of acute kidney injury (26,42). Historically, P. knowlesi infection was discovered as a naturally occurring human infection in Malaysia in 1965 (43).…”

“…Patients positive for malaria by PCR were classified as having severe malaria according to World Health Organization 2015 guidelines (https:// www.who.int/docs/default-source/documents/ publications/gmp/guidelines-for-the-treatment-ofmalaria-eng.pdf?sfvrsn=a0138b77_2). These guidelines define severe malaria as creatinine level >3 mg/dL, bilirubin level >3 mg/dL, bicarbonate level <15 mmol/L, hemoglobin level <7 g/dL for adults and <5 g/dL for children, parasite count 10%, hypoglycemia <2.2 mM, substantial bleeding, impaired consciousness, shock, prostration (defined as myalgia and arthralgia), multiple convulsions, and pulmonary edema) (26). The remaining patients were classified as having mild malaria.…”

“…We constructed a map of India based on the official maps provided by the Survey of India (http://www. surveyofindia.gov.in/pages/display/235-politicalmap-of-india), as described previously (26). In brief, we downloaded an India map shapefile (http://www.…”

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

“…64,65 Renal biopsies have also demonstrated malaria pigment and parasite DNA in the kidney tissue of patients with severe malaria-associated AKI. 66 These findings are supported by studies in adults and children with severe malaria with elevated levels of cellfree hemoglobin and free heme in severe malaria patients with AKI. [67][68][69][70] Hemolysis-mediated kidney injury occurs due to increased oxidative stress, inflammation, endothelial dysfunction, and reduced nitric oxide bioavailability (reviewed in 71 ), all of which are implicated in severe malaria pathogenesis.…”

“…61 Renal biopsies have demonstrated vascular changes, including cortical necrosis, tubular necrosis, and thrombotic microangiopathy in kidney tissue of patients with AKI, supporting a central role for vascular involvement in AKI. 66 An accumulation of uremic toxins is associated with endothelial damage and microvascular injury in AKI. 73 Endothelial activation is a central feature of severe malaria pathogenesis and is strongly associated with AKI in severe malaria.…”