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

Morbidity Due to Schistosoma Infection

The clinical manifestations of schistosomiasis can be grouped into several phases, and they differ between people living in endemic areas and nonimmune travelers upon primary infection. In the earliest stage, a cutaneous rash might develop at the site where the percutaneous penetration of the cercariae occurred. This localized eruption typically appears within the first week of infection and disappears after some hours. A first generalization of disease can be seen in the so-called 'Katayama fever' (sometimes also referred to 'Katayama syndrome'), which is named after a Japanese district that was once endemic for schistosomiasis japonica.[31] This immune-mediated syndrome constitutes a hypersensitivity reaction and may develop around 2–8 weeks after Schistosoma infection when maturing schistosomes migrate within the host and start egg production. Katayama fever is mainly seen in nonimmune individuals after their first exposure to schistosomes, and hence is an important differential diagnosis in returning travelers with fever. However, Katayama fever is rarely seen in endemic areas.[32] Despite the syndrome's name, fever is absent in at least one-third of symptomatic patients, and a good knowledge of other typical symptoms is mandatory to suspect acute schistosomiasis in affected individuals.[33] Dry cough, abdominal pain, general fatigue, myalgia, headache and diarrhea or abdominal tenderness are commonly seen and often accompanied by a peripheral blood eosinophilia.[34] Severe, possibly life-threatening complications are rare and include cardiac and central nervous involvement. Table 1 summarizes the clinical symptomatology of acute schistosomiasis.

Although acute schistosomiasis is a relevant health problem in returning travelers, morbidity due to chronic schistosomiasis is by far more significant in affected populations who live in schistosome-endemic areas. Adult schistosomes produce and excrete eggs, about half of which get trapped in small blood vessels of the bladder (S. haematobium) or liver (S. japonicum and S. mansoni) where the eggs and their secretions constitute a continuous antigenic stimulus, leading to granuloma formation around the eggs as an attempt to protect the affected organs from damage.[35] This persistent inflammatory immune response mechanism, however, leads to chronic genitourinary and renal disease (S. haematobium) as well as hepatic, gastrointestinal and even pulmonary morbidity (other species). Chronic complications account for most of the schistosomiasis burden.[4,36,37]Schistosoma mansoni and S. japonicum commonly cause hepatic fibrosis that favors the development of portal hypertension with devastating health consequences, such as variceal bleeding and hypersplenism, whereas S. haematobium typically leads to bladder lesions.[38] Inflammation and ulceration of the bladder give rise to persistent hematuria and dysuria, and the ever present urothelial alterations constitute an important risk factor for the development of squamous cell bladder cancer. Obstructive changes of the bladder wall in hosts chronically infected with S. haematobium might eventually lead to life-threatening upstream renal complications (hydronephrosis, nephrotic syndrome and glomerulonephritis).[38,39] In contrast, bloody diarrhea, colonic obstruction and abdominal pain are common features of S. mansoni and S. japonicum infections. Much less frequent, aberrant schistosome oviposition (all species) leads to neuroschistosomiasis that may present as acute paraplegia (when the spinal cord is affected) or encephalomyelitis (when brain involvement occurs).[40,41]

The chronic complications of schistosomiasis only occur after years of infection, and hence are generally seen in the adult population. However, schistosomiasis has an enormous impact on SAC and preschool-aged children (PSAC). Although SAC are the age group in which the highest prevalence and intensities of infection are usually observed,[42] there is growing recognition that PSAC might be considerably affected by schistosomiasis where the disease is highly endemic.[43,44] Negative effects on the nutritional status and anemia, impaired cognitive development, reduced physical fitness and higher susceptibility to co-infections have been reported.[37,45] However, subtle morbidity is much more complex to assess than specific organ alterations, and the causal attribution to a chronic infection is difficult. Most frequently, cognition is assessed by a battery of tests examining the learning and memory domains,[46] whereas the physical fitness can be assessed by using quality of life questionnaires and measurement of the oxygen uptake in a standardized 20-m shuttle run test.[47–50] Infants and PSAC are estimated to be most heavily affected by growth faltering and chronic morbidity, and recent epidemiological studies found that schistosomiasis can be quite prevalent in this age group.[43,51–54] However, research and schistosomiasis control activities have largely neglected PSAC.

Discussion Point

There is a paucity of high-quality, confounder-controlled studies examining morbidity in SAC and PSAC, and additional scientific evidence base with regard to a potentially negative impact of schistosomiasis on aerobic fitness and children's cognition needs to be generated. Growing awareness that schistosomiasis affects children at very young age will hopefully lead to new research in this neglected age group to further our understanding of the epidemiology and the acute and chronic morbidity patterns. Due to the manifold clinical manifestations of schistosomiasis, clinicians may not recognize the disease in young patients presenting with diffuse symptomatology. Hence, there is a need for the development of easily applicable algorithms for diagnosis and treatment of common syndromes in resource-constrained settings. Such algorithms should take schistosomiasis into account whenever necessary, for example, for the assessment of persistent diarrhea[55] or unexplained neurological disorders,[56] to improve our knowledge of its contribution to common clinical problems in schistosome- endemic countries. The 5-year multicountry NIDIAG study, funded by the European Commission (EC), aims to develop improved diagnosis–treatment algorithms for three clinical syndromes that frequently occur in resource-constrained tropical settings (i.e., persistent fever, neurological disorders and digestive disorders).[302] Hence, ongoing research by the NIDIAG consortium will contribute to fill an important identified gap.

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