Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella During Current or Convalescent Plasmodium falciparum Infection in Malawian Children (original) (raw)
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016
Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2...
Scientific Reports, 2021
Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence ...
Parasitology Research, 2019
Malaria-associated bacteremia accounts for up to one-third of deaths from severe malaria, and non-typhoidal Salmonella (NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during Plasmodium infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial or endothelial sites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry. P. chabaudi infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice. Plasmodium infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to P. chabaudi infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.
East African Health Research Journal
Background: Plasmodium falciparum and Salmonella typhi are major causes of fever in the tropics. Although these infections are caused by different organisms and are transmitted via different mechanisms, they have similar epidemiologic and clinical features. This study aimed to determine the prevalence of S. typhi and P. falciparum infections and their associations with fever at 2 sites in Northern Tanzania. Methods: This was a community-based, cross-sectional study, conducted from February to June 2016, involving 128 randomly selected individuals, aged between 1 and 70 years. Sixty-three (49.2%) participants were recruited from Bondo Ward, Tanga Region, and 65 (50.8%) were recruited from Magugu Ward, Manyara Region. Blood samples were collected by venepuncture into sterile microtubes. Detection of pathogen DNA was achieved via a multiplex real-time polymerase chain reaction assay. Data analysis was done using Stata, version 14. Prevalence data were presented as numbers and percentages, and chi-square analysis was used to assess associations. P values of .05 or less were considered statistically significant. Results: Of 128 participants, 31 (24.2%) and 17 (13.3%) tested positive for P. falciparum and S. typhi infection, respectively. Of the 63 participants from Bondo, 31 (49.2%) had P. falciparum parasitaemia. None of the participants from Magugu tested positive for Plasmodium parasitaemia. S. typhi bacteraemia was detected in 11 (17.5%) of 63 and 6 (9.2%) of 65 participants in Bondo and Magugu, respectively. P. falciparum-S. typhi coinfection was only detected in Bondo (n=6, 9.5%). Age was the only variable that showed a significant association with both P. falciparum and S. typhi infection; falling within the 5-to 9-year or 10-to 15-year age groups was associated with both infections (X 2 =2.1; P=.045). Among the 30 patients with Plasmodium parasitaemia, 7 (23.3%) had fever, whereas 2 (12.5%) of 16 patients infected by S. typhi had fever. P. falciparum infection (X 2 =12.4, P<.001) and P. falciparum-S. typhi coinfection (X 2 =5.5, P=.019) were significantly associated with fever, while S. typhi infection alone was not. Conclusion: S. typhi and P. falciparum were considerably prevalent in the area. One-third of the P. falciparum-S. typhi coinfected individuals in Bondo had fever. P. falciparum infection was an important contributor to febrile illness in Bondo. In the presence of coinfections with P. falciparum and S. typhi, the use of malaria rapid diagnostic tests should be emphasised to reduce irrational use of medications.
Infection and Immunity, 2010
Severe pediatric malaria is an important risk factor for developing disseminated infections with nontyphoidal Salmonella serotypes (NTS). While recent animal studies on this subject are lacking, early work suggests that an increased risk for developing systemic NTS infection during malaria is caused by hemolytic anemia, which leads to reduced macrophage microbicidal activity. Here we established a model for oral Salmonella enterica serotype Typhimurium challenge in mice infected with Plasmodium yoelii nigeriensis. Initial characterization of this model showed that 5 days after coinoculation, P. yoelii nigeriensis infection increased the recovery of S. Typhimurium from liver and spleen by approximately 1,000-fold. The increased bacterial burden could be only partially recapitulated by antibody-mediated hemolysis, which increased the recovery of S. Typhimurium from liver and spleen by 10-fold. These data suggested that both hemolysis and P. yoelii nigeriensis-specific factors contributed to the increased susceptibility to S. Typhimurium. The mechanism by which hemolysis impaired resistance to S. Typhimurium was further investigated. In vitro, S. Typhimurium was recovered 24 h after infection of hemophagocytic macrophages in 2-fold-higher numbers than after infection of mock-treated macrophages, making it unlikely that reduced macrophage microbicidal activity was solely responsible for hemolysis-induced immunosuppression during malaria. Infection with P. yoelii nigeriensis, but not antibodymediated hemolysis, reduced serum levels of interleukin-12p70 (IL-12p70) in response to S. Typhimurium challenge. Collectively, studies establishing a mouse model for this coinfection suggest that multiple distinct malaria-induced immune defects contribute to increased susceptibility to S. Typhimurium.
Sumerianz Journal of Biotechnology, 2021
Study on the prevalence of co-infection between Plasmodium falciparum and Salmonella typhi among patients in Northern Nigeria was carried out. The study is cross-sectional designed to determine the socio-demographic characteristics as well as the risk factors for malaria and typhoid. A total of 100 consented patients of age group of 21-40 years were recruited for the study. A structured questionnaire was administered, and venous blood samples were collected and analyzed using standard microbiological methods. The isolated salmonella species were biochemically characterized, and subjected to antimicrobial susceptibility test using Kirby-Bauer disc diffusion method. The prevalence of malaria and typhoid was found to be 56% and 68% respectively. The prevalence of malarial parasite and Salmonella typhi infections was 40%. Females recorded low malarial infection of 56.9% compared to their male counterparts 43.1% (P= 0.510). The age group, educational levels and occupations of the study participants were not associated with the likelihood of having malarial parasite infection (P= 0.297, 0.15 and 0.503 respectively). Participants who did not sleep under the insecticide treated nets were more likely to have malaria than those who did (P ≤ 0.0001). The educational levels of the study participants were statistically associated with Salmonella typhi infection (P= 0.026). Water sources, use of pit latrine, hand washing before and after meal were significantly associated with Salmonella typhi infections (P= <0.0001 and P= 0.003 respectively). The isolates of Salmonella typhi and Salmonella paratyphi were found to be sensitive to chloramphenicol (86.8%), ciprofloxacin (80.9%) and amoxicillin (79.4%), but relatively resistant to penicillin and augmentin that recorded sensitivities of 19.1% and 35.3% respectively. The prevalence of malaria and typhoid infections as well as malarial parasite and Salmonella typhi co-infections is high among the study population. Fortunately, the isolated bacteria are highly sensitive to chloramphenicol and ciprofloxacin.
Mediators of inflammation, 2016
Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[-]) enteric Bacilli and Plasmodium falciparum (Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/μL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n = 206, aged <3 yrs): healthy; Pf[+] alone; G[-] coinfected; and G[+] coinfected. Staphylococcus aureus and non-Typhi Salmonella were the most frequently isolated G[+] and G[-] organisms, respectively. Coinfected children, particularly those with G[-] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-α and decreased TNF-α relative to ma...