Severe Malaria in Contemporary Times: Etiologies, Tools, and Translational Research

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Public Health Microbiology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 3907

Special Issue Editor


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Guest Editor
School of Medicine, University of St Andrews, Medical and Biological Sciences Building, North Haugh, St Andrews KY16 9TF, UK
Interests: Plasmodium knowlesi; malaria and other parasites of the tropics; innate immune response in malaria infection; comparative genetics; cloning, sequencing, haplotyping; molecular epidemiology of malaria parasites; development of sensitive molecular tools for blood-borne parasite detection; stage-specific expression of parasite surface proteins; third generation MinION genome sequencing, emerging infectious diseases; pathogen genomics; virulence and pathophysiology

Special Issue Information

Dear Colleagues,

The health burden of malaria is the sum of a myriad of complex component parts from parasite species and intraspecies diversity, through location, climate, economics, and infrastructures to informed care options for the severely ill. 

The complexity and geographic spread of malaria are reflected in the disjointed and indeed limited information available to specifically tackle the urgent medical needs of the acutely ill.

The most recent figures released by the World Health Organization (WHO) to evaluate the global burden of malaria (2020) are: 241 million cases, 95% of which are in the WHO African region; 627,000 deaths, 96% in the WHO African Region and 80% of those in children younger than 5 years old.  The numbers are grim and translate into at least 501,600 children under the age of 5 years having died in the year 2020 as a direct result of acute malaria.  This represents 8% of all deaths globally in 1–59-month-olds; however, the numbers for malaria deaths in this age group are not global but concentrated in the malaria endemic areas of African nations.

Children, pregnant women, and the unborn are most vulnerable to malaria in endemic areas, and one Plasmodium species in particular is the most harmful: Plasmodium falciparum.

This Special Issue on ‘Severe Malaria’ aims to assemble a collection of articles and reviews representing the multiple disciplines striving to reduce the health burden of malaria and, in particular, those focusing on malaria pathophysiology, anemia, and translational pathways to benefit human health. How can we best develop therapies to save those acutely ill with severe malaria?

Dr. Janet Cox-Singh
Guest Editor

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Keywords

  • severe malaria
  • virulence
  • anemia
  • pathophysiology
  • poverty
  • non-human primate models
  • translational research
  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium knowlesi
  • gene editing
  • disease phenotyping

Published Papers (2 papers)

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Research

16 pages, 1554 KiB  
Article
Respiratory Distress Complicating Falciparum Malaria Imported to Berlin, Germany: Incidence, Burden, and Risk Factors
by Bodo Hoffmeister
Microorganisms 2023, 11(6), 1579; https://doi.org/10.3390/microorganisms11061579 - 14 Jun 2023
Cited by 1 | Viewed by 1184
Abstract
While European healthcare systems face resource shortages as a consequence of the coronavirus pandemic, numbers of imported falciparum malaria cases increased again with re-intensifying international travel. The aim of the study was to identify malaria-specific complications associated with a prolonged intensive care unit [...] Read more.
While European healthcare systems face resource shortages as a consequence of the coronavirus pandemic, numbers of imported falciparum malaria cases increased again with re-intensifying international travel. The aim of the study was to identify malaria-specific complications associated with a prolonged intensive care unit (ICU) length of stay (ICU-LOS) in the pre-COVID-19 era and to determine targets for their prevention. This retrospective observational investigation included all the cases treated from 2001 to 2015 at the Charité University Hospital, Berlin. The association of malaria-specific complications with the ICU-LOS was assessed using a multivariate Cox proportional hazard regression. The risk factors for the individual complications were determined using a multivariate Bayesian logistic regression. Among the 536 included cases, 68 (12.7%) required intensive care and 55 (10.3%) suffered from severe malaria (SM). The median ICU-LOS was 61 h (IQR 38–91 h). Respiratory distress, which occurred in 11 individuals (2.1% of the total cases, 16.2% of the ICU patients, and 20% of the SM cases), was the only complication independently associated with ICU-LOS (adjusted hazard ratio for ICU discharge by 61 h 0.24, 95% confidence interval, 95%CI, 0.08–0.75). Shock (adjusted odds ratio, aOR, 11.5; 95%CI, 1.5–113.3), co-infections (aOR 7.5, 95%CI 1.2–62.8), and each mL/kg/h fluid intake in the first 24 treatment hours (aOR 2.2, 95%CI 1.1–5.1) were the independent risk factors for its development. Respiratory distress is not rare in severe imported falciparum malaria, and it is associated with a substantial burden. Cautious fluid management, including in shocked individuals, and the control of co-infections may help prevent its development and thereby reduce the ICU-LOS. Full article
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20 pages, 1187 KiB  
Article
Pediatric Malaria with Respiratory Distress: Prognostic Significance of Point-of-Care Lactate
by Catherine Mitran, Robert O. Opoka, Andrea L. Conroy, Sophie Namasopo, Kevin C. Kain and Michael T. Hawkes
Microorganisms 2023, 11(4), 923; https://doi.org/10.3390/microorganisms11040923 - 2 Apr 2023
Viewed by 2325
Abstract
Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed [...] Read more.
Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed a pooled analysis of Ugandan children under five years of age hospitalized with malaria and RD from three past studies. In total, 1324 children with malaria and RD (median age 1.4 years, 46% female) from 21 health facilities were included. Median lactate level at admission was 4.6 mmol/L (IQR 2.6–8.5) and 586 patients (44%) had hyperlactatemia (lactate > 5 mmol/L). The mortality was 84/1324 (6.3%). In a mixed-effects Cox proportional hazard model adjusting for age, sex, clinical severity score (fixed effects), study, and site (random effects), hyperlactatemia was associated with a 3-fold increased hazard of death (aHR 3.0, 95%CI 1.8–5.3, p < 0.0001). Delayed capillary refill time (τ = 0.14, p < 0.0001), hypotension (τ = −0.10, p = 0.00049), anemia (τ = −0.25, p < 0.0001), low tissue oxygen delivery (τ = −0.19, p < 0.0001), high parasite density (τ = 0.10, p < 0.0001), and acute kidney injury (p = 0.00047) were associated with higher lactate levels. In children with malaria and RD, bedside lactate may be a useful triage tool, predictive of mortality. Full article
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