Abstract
Plasmodium falciparum malaria and non-typhoid Salmonella (NTS) bacteraemia are both major causes of morbidity and mortality in children in sub-Saharan Africa. Co-infections are expected to occur because of their overlapping geographical distribution, but accumulating evidence indicates that malaria is a risk factor for NTS bacteraemia. A literature review was undertaken to provide an overview of the evidence available for this association, the epidemiology of malaria-NTS co-infection (including the highest risk groups), the underlying mechanisms, and the clinical consequences of this association, in children in sub-Saharan Africa. The burden of malaria-NTS co-infection is highest in young children (especially those less than three years old). Malaria is one of the risk factors for NTS bacteraemia in children, and the risk is higher with severe malaria, especially severe malarial anaemia. There is insufficient evidence to determine whether asymptomatic parasitaemia is a risk factor for NTS bacteraemia. Many mechanisms have been proposed to explain how malaria causes susceptibility to NTS, ranging from macrophage dysfunction to increased gut permeability, but the most consistent evidence is that malarial haemolysis creates conditions which favour bacterial growth, by increasing iron availability and by impairing neutrophil function. Few discriminatory clinical features have been described for those with malaria and NTS co-infection, except for a higher risk of anaemia compared to those with either infection alone. Children with malaria and NTS bacteraemia co-infection have higher case fatality rates compared to those with malaria alone, and similar to those with bacteraemia alone. Antimicrobial resistance is becoming widespread in invasive NTS serotypes, making empirical treatment problematic, and increasing the need for prevention measures. Observational studies indicate that interventions to reduce malaria transmission might also have a substantial impact on decreasing the incidence of NTS bacteraemia.
Highlights
There are thousands of serotypes of Salmonella, including those grouped as Salmonella enterica subspecies enterica, which can cause disease in humans, and are normally dichotomized into those causing typhoid fever (i.e., S. enterica subsp. enterica serotype Typhi, and Paratyphi), and non-typhoid salmonella (NTS) serotypes which include Enteritidis and Typhimurium [1,2]
Numerous hospitalbased studies have shown higher prevalence of malaria parasites among children hospitalized with non-typhoid Salmonella (NTS) compared to other bacteraemia/other admitted children [6,13,15,16,20,21], or a higher prevalence of NTS bacteraemia among those with malaria parasites compared to aparasitaemic children [4,22,23], but their interpretation is very challenging, as they could be subject to selection bias
Mor rapid diagnostic test (RDT) More NTS in rainy season; recent malaria (RDT positive) but not current bacteraemia malaria was a risk factor for NTS bacteraemia compared to nonbacteraemic patients (OR = 1.8, 95% CI 1.0-3.1)
Summary
There are thousands of serotypes of Salmonella, including those grouped as Salmonella enterica subspecies enterica, which can cause disease in humans, and are normally dichotomized into those causing typhoid fever (i.e., S. enterica subsp. enterica serotype Typhi, and Paratyphi), and non-typhoid salmonella (NTS) serotypes which include Enteritidis and Typhimurium [1,2]. Most of the epidemiological evidence in humans is based on these studies, and on studies showing parallel decreases in incidence of malaria and NTS bacteraemia in the same geographical area over time [18,19]. One of these published reports included suitable community controls [14]. Other Plasmodium species are less common, and their association with NTS has not been systematically studied Both pathophysiological and/or epidemiological factors may account for the absence of any reported association, there are a few reports of bacteraemia and P. vivax co-infection outside sub-Saharan Africa [39]. These taken together, may suggest that, malaria increases the risk of NTS bacteraemia in those who are already infected (carriers) rather than increasing the risk of carriage of NTS, but further studies are needed to confirm this hypothesis
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