Diagnosis and Treatment of Schistosomiasis in Children in the Era of Intensified Control

Stefanie Knopp; Sören L Becker; Katrin J Ingram; Jennifer Keiser; Jürg Utzinger

Disclosures

Expert Rev Anti Infect Ther. 2013;11(11):1237-1258. 

In This Article

Schistosomiasis Co-infections

In most schistosome-endemic areas, several other viral, bacterial and parasitic pathogens are commonly found, thus leading to a substantial amount of co-infections. The impact of multiple concurrent infections on acute and chronic morbidity and on the susceptibility to other infections is poorly understood and thus constitutes an important research need. We present some key co-infections and discuss their clinical significance.

HIV/AIDS

Experimental studies in mice and monkeys led to the hypothesis that S. mansoni infections would accelerate replication of HIV and possibly the clinical course in co-infected individuals.[45] These observations are generally explained by the effects of schistosomiasis on the host's immune response, specifically on the two important subsets of CD4-positive T lymphocytes, that is, Th1 and Th2.[202] Intestinal schistosomiasis stimulates the Th2-type cytokine production (e.g., interleukins 4, 5 and 13) that leads to eosinophilia. In contrast, the Th1-type response (e.g., cytotoxic T lymphocytes, γ-interferon production) is reduced, which results in less efficient control of HIV replication in the host. Additionally, mast cells of the intestinal mucosa have been identified as a potential link between HIV infection and schistosomiasis.[203] Although the exact immunological mechanisms still need to be elucidated, there is a growing body of evidence from clinical and epidemiological studies of a cause–effect relationship between both urogenital and intestinal schistosomiasis and HIV infection. Schistosomiasis appears to favor an elevated susceptibility to HIV, a more rapid disease progression, and transmission of HIV to others.[45,204] The potential public health impact of antischistosomal treatment, particularly preventive chemotherapy targeting entire communities, on HIV/AIDS remains to be elucidated.

Viral Hepatitis

Viral hepatitis and schistosomiasis are co-endemic in many tropical areas. The hepatitis B and C viruses share some important features with schistosomiasis, particularly the hepatotropism and the high rate of chronic infections. Co-infections are common,[205] yet rarely taken into account in the clinical assessment of patients from co-endemic areas.[206] A schistosome co-infection in patients with hepatitis C is significantly associated with failure to respond to antiviral therapy.[207] Similar to tuberculosis, schistosomiasis might alter the host's immune response, thus leading to a weak or absent response to the hepatitis B vaccine. A recent in vivo study with S. japonicum in the mouse model demonstrated that this inhibited vaccine response was reversible following anthelmintic treatment, thus underscoring the potential of periodic deworming as an important public health measure in co-endemic areas.[208]

Tuberculosis

A study from Tanzania reported a co-infection with S. mansoni in every third hospitalized patient with tuberculosis.[209] Moreover, several studies made an interesting observation according to which schistosomiasis may reduce the host's immune response to the bacille calmette–guerin vaccine, which is widely used in endemic areas for protection against Mycobacterium tuberculosis, and hence may lower the protective efficacy of the vaccine.[210]

Salmonellosis

Typhoidal and nontyphoidal serovars of Salmonella enterica, a Gram-negative bacterium, are important water- and foodborne pathogens of diarrheal and systemic infections, with the highest morbidity observed in tropical and subtropical areas. Systemic infections can often be fatal and require immediate antibiotic treatment. In co-infected patients where both Salmonella and adult schistosomes are present in blood vessels, the bacterium can attach to the parasite's tegument via a specific fimbrial adherence protein. Interestingly, this docking mechanism protects Salmonella against systemic antibiotic therapy. Several studies found that different antibiotics commonly used to treat salmonellosis were not effective in individuals co-infected with schistosomiasis. Even if antibiotics tested to be active against Salmonella strains in vitro were administered, they were of no clinical use to cure salmonellosis.[211] Moreover, once the refuge-providing schistosomes are eliminated following praziquantel treatment, life-threatening Salmonella bacteremia may rapidly develop in co-infected patients.[212] Hence, this co-infection is of considerable clinical relevance and new research is urgently required.

Malaria (Infection With Plasmodium spp.)

A considerable amount of work has been carried out over the past decade to investigate potential links between malaria and schistosomiasis (and other helminth infections). Although many studies suggest a positive association between the infection intensities in people harboring a concurrent PlasmodiumSchistosoma infection,[213,214] others reported antagonistic results. For example, in comparison to individuals without schistosomiasis, a Senegalese study observed less severe P. falciparum infection intensities in children who were co-infected with S. haematobium at a light intensity.[215] Such conflicting results may be due to the fact that most co-infection studies were carried out in SAC or adults, while there is a paucity of data in very young children who are at highest risk of developing severe malaria. Hence, studies of malaria in schistosomiasis- endemic regions in PSAC have been identified as an urgent research need for a comprehensive understanding of the interactions between both parasites.[216]

Soil-transmitted Helminthiasis

Co-infections between schistosomes and the soil-transmitted helminths (i.e., Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis and hookworm) have been studied in laboratory animals and humans. Data are conflicting with some studies reporting a multiplication of disease severity, whereas in other studies, infection with one helminth appeared to confer protection from a subsequent infection with another helminth species. However, epidemiological studies observed a strong association between hookworm and S. mansoni co-infection[217,218] and higher infection intensities and elevated levels of anemia in co-infected individuals.[217,219] Moreover, several recent case reports draw attention to severe co-infections of S. mansoni and S. stercoralis that warrant further investigation.[220,221]

Other Infections

Co-infection studies have been conducted for several other bacteria (e.g., Helicobacter pylori and Staphylococcus aureus), protozoa (e.g., Entamoeba, Leishmania and Toxoplasma) and helminths (e.g., Fasciola and Echinostoma).[222] Very recently, a first report suggested an association between schistosomiasis and eumycetoma, a neglected fungal disease that frequently occurs in tropical settings.[223]

Discussion Point

There is ample evidence for associations (positive and negative) and interactions between schistosomiasis and other infectious diseases, and many of them are co-endemic in tropical and subtropical areas. The health effects of schistosomiasis are not limited to the disease itself, but also the trematodes' ability to negatively influence on the course and prognosis of other infections and to impair the effectiveness of preventive measures such as vaccines. There is a particular lack of research targeting the interactions between schistosomiasis and viral hepatitis, tuberculosis and invasive salmonellosis. Hence, in-depth experimental studies and well-designed epidemiological studies should be launched without delay. Moreover, studies assessing the impact of praziquantel treatment on the incidence and severity of the aforementioned co-infections in populations with different Schistosoma infection levels are sorely needed. The EC-funded multicountry IDEA project will generate new evidence about the interaction of schistosomiasis with HIV, tuberculosis and malaria and the impact of antischistosomal treatment on disease outcome and immunological markers.[304] Indeed, IDEA will longitudinally follow-up well-characterized HIV, tuberculosis and malaria cohorts, and study the effect of helminth co-infections, which are rigorously assessed by a suite of diagnostic methods (i.e., examination of stool and urine samples with a broad set of quality-controlled parasitological methods).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....