Background: Despite the high infectivity of SARS-CoV-2, the incidence of COVID-19 in Africa has been slower than predicted. We aimed to investigate a possible association between parasitic infections and COVID-19. Results:Of the global 3.34 million COVID-19 cases and 238,628 deaths as at May 4 th 2020, Africa reported 0.029/3.3 million (0.88%) cases and 1,064/238,628 (0.45%) deaths. In 2018, Africa reported 213/229 million (93%) of all malaria cases, 204/229 million (89%) of schistosomiasis cases, and 271/1068 million (25%) of soil-transmitted helminth cases globally. In contrast, Europe reported 1.5/3.3 million (45%) of global COVID-19 cases and 142,667/238,628 (59%) deaths. Europe had 5.8/1068 million (0.55%) soil-transmitted helminths cases and no malaria/schistosomiasis cases in 2018. We found an inverse correlation between the incidence of COVID-19 and malaria (r -0.17, p =0.002) and COVID-19 and soil-transmitted helminths (r -0.25, p <0.001). Malaria-endemic countries were less likely to have COVID-19 (OR 0.51, 95% CI 0.29-0.90; p =0.02). Similarly, countries endemic for soil-transmitted helminths were less likely to have COVID-19 (OR 0.24, 95% CI 0.13-0.44; p <0.001), as were countries endemic for schistosomiasis (OR 0.22, 95% CI 0.11-0.45; p<0.001). Conclusions:One plausible hypothesis for the comparatively low COVID-19 cases/deaths in parasite-endemic areas is immunomodulation induced by parasites. Studies to elucidate the relationship between parasitic infections and susceptibility to COVID-19 at an individual level are warranted.

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.

Radiation‐attenuated sporozoites induce sterilizing immunity and remain the 'gold standard' for malaria vaccine development. Despite practical challenges in translating these whole sporozoite vaccines to large‐scale intervention programmes, they have provided an excellent platform to dissect the immune responses to malaria pre‐erythrocytic (PE) stages, comprising both sporozoites and exoerythrocytic forms. Investigations in rodent models have provided insights that led to the clinical translation of various vaccine candidates—including RTS,S/AS01, the most advanced candidate currently in a trial implementation programme in three African countries. With advances in immunology, transcriptomics and proteomics, and application of lessons from past failures, an effective, long‐lasting and wide‐scale malaria PE vaccine remains feasible. This review underscores the progress in PE vaccine development, focusing on our understanding of host‐parasite immunological crosstalk in the tissue environments of the skin and the liver. We highlight possible gaps in the current knowledge of PE immunity that can impact future malaria vaccine development efforts.

Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a two-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10 [IQR 0.03, 0.19]) than those with CM (0.24 [0.14, 0.69]; P=0.006) or asymptomatic malaria (0.19 [0.09, 0.46]; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL [4.7, 49.8]) and hepcidin/ferritin ratios (0.03 [0.01, 0.22]) than those with NTS alone (105.8 ng/mL [17.3, 233.3]; P=0.02 and 0.31 [0.06, 0.66]; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole (SCV), we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidinferroportin axis might mediate susceptibility to NTS in severely anemic children.