Effects of ConcomitantSchistosoma haematobiumInfection on the Serum Cytokine Levels Elicited by AcutePlasmodium falciparumMalaria Infection in Malian Children

Abstract

Polyparasitism is common in the developing world, and interactions that alter disease severity may occur. We previously demonstrated that infection with Schistosoma hematobium was associated with protection against Plasmodium falciparum infection in children who were 4 to 8 years old. In this study, we determined whether underlying helminth infections affected the cytokine responses to acute falciparum malaria. A total of 338 schistosomiasis-positive [Sch(؉)] children who were 4 to 14 years old were matched by age, residence, and sex with 338 schistosomiasis-negative [Sch(؊)] children and monitored for a malaria transmission season (25 weeks). Serologic cytokine levels were measured at the time of the first clinical malaria episode and in children who did not contract malaria. Elevated background levels of interleukin-6 (IL-6) (37.1 pg/ml versus 10.9 pg/ml [P ‫؍‬ 0.04]), IL-4 (27.7 pg/ml versus 6.9 pg/ml [P ‫؍‬ 0.02]), IL-10 (18.2 pg/ml versus 7.2 pg/ml [P < 0.001]), and gamma interferon (18.2 pg/ml versus 4.7 pg/ml [P ‫؍‬ 0.006]) were noted in Sch(؉) children compared to Sch(؊) children without malaria. IL-6 and IL-10 levels were elevated in association with acute malaria, but the levels appeared to be blunted in Sch(؉) children compared to Sch(؊) children who were 4 to 8 years old (for IL-6, 96.2 pg/ml versus 137.2 pg/ml [P ‫؍‬ 0.08]; for IL-10, 195.9 pg/ml versus 282.2 pg/ml [P ‫؍‬ 0.06]). The level of IL-10 was similarly lower in Sch(؉) children than in Sch(؊) children who were 9 to 14 years old (91.2 pg/ml versus 141.2 pg/ml [P ‫؍‬ 0.03]). IL-4 levels were inversely correlated with the time until the first malaria infection in both the Sch(؉) children (P < 0.001) and the Sch(؊) children (P < 0.001) who were 4 to 8 years old. We postulate that the Th2-enriched environment induced by schistosomiasis protects against malaria and alters the cytokine milieu during an actual infection.

Coinfection with Plasmodium falciparum and Schistosoma haematobium: Additional Evidence of the Protective Effect of Schistosomiasis on Malaria in Senegalese Children

“…23 A study on children conducted in Mali in 2002-2003 presented both epidemiological and biological approaches and concluded on a protective effect of infection with urinary schistosomiasis on malaria. 8,9 In contrast, other studies suggested an additive or synergistic effect of coinfection.…”

“…[4][5][6]17 In this study, we focused on the interaction between schistosomiasis and malaria infection. Several biological studies have shown a synergistic effect of coinfection, 16,[18][19][20][21] whereas other studies suggested an acceleration or regulation toward protective profile of the acquired immunity against malaria in children coinfected with malaria and schistosomiasis 9,22 and another study did not find an association. 23 A study on children conducted in Mali in 2002-2003 presented both epidemiological and biological approaches and concluded on a protective effect of infection with urinary schistosomiasis on malaria.…”

“…7 Another study among children in Mali in [2002][2003] with both an epidemiological and a biological approach, showed an age-dependent protection in children infected with urinary schistosomiasis against acute P. falciparum malaria. 8,9 However, other studies suggested an additive or synergic effect of coinfection, 10,11 as for example, Wilson and others 11 who showed that concurrent chronic exposure to Schistosoma mansoni and P. falciparum could have a synergistic effect on childhood morbidity.…”

Pathogen Interactions, Population Cycles, and Phase Shifts

“…This has led to suggestions that interspecific interactions are of little importance in shaping pathogen communities under natural conditions [6][7][8][9][10][11][12][13][14][15][16]. This debate continues despite the fact that the importance of pathogen interactions is becoming increasingly obvious in clinical settings [17][18][19][20][21]. One possible explanation for the apparent lack of interactions between pathogen species in wild host systems is that the pathogens may be temporally asynchronous within their hosts, resulting in a form of niche segregation and reducing the likelihood of direct interaction [12,22].…”

Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens

“…However, studies that have assessed this question have yielded conflicting results indicating that larger and better designed studies are needed. [17][18][19][20] To date, studies assessing the coinfection of helminths and malaria have mainly focused on the asexual forms of P. falciparum (reviewed in reference 21). However, there are indications that helminth infections may also influence the prevalence or density of P. falciparum gametocytes, the parasite stage responsible for transmission of infections to mosquitoes.…”