Schistosomiasis: Treatment and prevention

INTRODUCTION — Schistosomiasis is a disease caused by infection with parasitic blood flukes. The three major species are Schistosoma mansoni (Africa and South America), Schistosoma japonicum (East Asia), and Schistosoma haematobium (Africa and the Middle East). The four minor species are Schistosoma mekongi (Laos, Cambodia), Schistosoma malayi (Peninsular Malaysia), Schistosoma intercalatum, and Schistosoma guineensis (West and Central Africa).

The treatment and prevention of schistosomiasis will be reviewed here. The epidemiology, pathogenesis, clinical features, and diagnosis of schistosomiasis are discussed separately. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis".)

TREATMENT — Treatment of schistosomiasis serves three purposes: reversing acute or early chronic disease, preventing complications associated with chronic infection, and preventing neuroschistosomiasis. The goal of treatment is reduction of egg production via reduction of worm load; this reduces morbidity and mortality even in the absence of complete worm eradication [1]. In endemic areas, repeated treatment is essential for schistosomiasis elimination [2].

Benefits of treatment include reversal of hydronephrosis and regression of periportal fibrosis in its early stage [3]. However, anthelmintic treatment has little effect on reversing late-stage fibrosis of the hepatic or urinary tract or reversing secondary complications such as portal hypertension with esophageal varices or cor pulmonale.

Clinical approach

Acute infection

Swimmer's itch — Swimmer's itch is usually caused by repeated exposure to nonhuman schistosome species; humans are not suitable hosts, so the organism dies while in the skin. The rash typically clears within a few days; treatment consists of symptomatic management for pruritus. (See "Pruritus: Therapies for localized pruritus".)

Acute schistosomiasis syndrome — Acute schistosomiasis syndrome (also known as Katayama fever) is a systemic hypersensitivity reaction to schistosome antigens and circulating immune complexes that occurs three to eight weeks after infection; clinical manifestations are discussed further separately. (See "Schistosomiasis: Epidemiology and clinical manifestations", section on 'Acute schistosomiasis syndrome'.)

Our approach to management of acute schistosomiasis syndrome is as follows:

●Initial management consists of reduction of inflammation with corticosteroids [4,5]. The optimal dose and duration of corticosteroids are uncertain; in general, we treat with prednisolone (1 mg/kg per day) until symptoms subside and for 48 hours thereafter (typically 3 to 10 days) [6,7].

●Subsequently, we favor administration of praziquantel (40 mg/kg once) 8 to 12 weeks after infection, together with prednisolone (1 mg/kg per day for 1 to 3 days), and only after the initial acute symptoms have been fully suppressed with corticosteroids alone. Failure to do so may cause symptoms to (re)appear [8-13].

Praziquantel is administered to prevent chronic infection and serious complications such as early neuroschistosomiasis [13,14]. Data on optimal timing of treatment are limited. In general, praziquantel is effective only when given at least 4 to 8 weeks following exposure (ie, once infection is well established and the worms have fully matured) [8]. In one animal model, praziquantel had no activity in the first 21 days after infection, low activity at day 28, and 100 percent activity at day 52 [15].

Corticosteroids are given with initial treatment because administration of praziquantel within 12 weeks after infection may be associated with aggravation of symptoms [4,9,16]. Corticosteroids reduce plasma levels of praziquantel; however, data are limited regarding whether the praziquantel dosing warrants adjustment in the setting of corticosteroids [17].

●Finally, we administer praziquantel (40 mg/kg once) once again four to six weeks later, but not earlier than three months after infection (without corticosteroids), to eliminate the remaining schistosomes that matured in the interim period since the previous treatment [10,12].

Chronic infection

Overview — Among individuals in endemic areas, the goal of treatment is to reduce parasite burden and morbidity (given that reinfection is unavoidable). Among individuals outside of endemic areas, the goal of treatment is definitive cure.

Patients with known recent exposure should have treatment deferred until diagnostic serology and/or microscopy can be performed (generally positive 6 to 12 weeks after exposure) and symptoms of acute disease (if present) have subsided. (See 'Acute schistosomiasis syndrome' above.)

In endemic areas, a single dose of praziquantel is curative in 20 to 100 percent of cases [18]; among individuals who are not cured, praziquantel reduces the parasite burden by 30 to 90 percent depending on the diagnostic methods used [18-23]. Retreatment of patients with residual infection only marginally increases cure rates [23-26].

Among travelers and expatriates, whose parasite burden is usually low, a single dose of praziquantel is generally sufficient to reduce the worm burden to negligible levels [12,27]. Some use higher doses for and/or prolonged duration of treatment; however, data to support this approach are limited [28].

Dosing of praziquantel for infection due to S. haematobium, S. mansoni, or S. intercalatum consists of 40 mg/kg in one or two (divided) doses [26]. Dosing for infection due to S. japonicum or S. mekongi consists of 60 mg/kg in two divided doses [19,20,27]. A repeat dose of praziquantel given two to six weeks after the initial dose may improve cure rate or further reduce the intensity of S. mansoni infection, although this is not a standard practice [28]. This may apply to other schistosome species as well.

Follow-up after treatment includes monitoring of clinical manifestations, eosinophil count (in patients with eosinophilia), microscopy evaluation for eggs in stool or urine. Neither serology nor serum polymerase chain reaction tests are suitable as a useful monitoring tool, as both remain positive for prolonged periods following treatment [10].

Eosinophil levels may increase shortly after treatment and subsequently decrease over several weeks [29]. Persistent eosinophilia for more than three months after treatment may reflect insufficient reduction of parasite burden and/or may indicate the presence of an additional helminth infection.

In endemic areas, follow-up microscopy of stool or urine for assessment of parasite load reduction and cure should be performed no sooner than six weeks following treatment. In nonendemic areas, follow-up microscopy may be performed three to six months after treatment, since there is no risk of intercurrent reinfection [30]. Egg excretion may continue for a few weeks after treatment and differentiating viable from nonviable eggs may be difficult. In addition, treatment may cause temporary cessation of egg production from adult worms that are not killed.

Presence of viable eggs 6 to 12 weeks after initial therapy warrants repeat treatment with praziquantel. The same dose of praziquantel (40 mg/kg for infection due to S. haematobium, S. mansoni, or S. intercalatum; 60 mg/kg for infection due to S. japonicum or S. mekongi) may be administered [27]. There does not appear to be an advantage to increasing the dose in retreatment [31,32].

In populations with a high parasite burden, radiographic imaging (abdominal ultrasound or magnetic resonance imaging) is essential to document long-term reversal of urinary tract lesions and of periportal liver disease following repeated mass treatment [33].

Detection of circulating anodic antigen in serum and urine offers a promising development in monitoring treatment efficacy in S. haematobium complex infection, but is not yet routinely available [34]. For S. mansoni, results of a point-of care circulating cathodic antigen urine test lacked sensitivity and specificity in low-endemic areas [35].

Issues related to population deworming are discussed separately. (See "Mass drug administration for control of parasitic infections", section on 'Clinical approach'.)

Genitourinary schistosomiasis — Urinary schistosomiasis can cause genital lesions during childhood. Repeated treatment with praziquantel may reverse such lesions, more so in younger patients [36]. Genital schistosomiasis increases vaginal mucosal fragility and bleeding in adult women and has been associated with increased risk of HIV acquisition in several studies [37]. While genital lesions in adults are chronic, it is assumed that early and repeated treatment with praziquantel could substantially reduce local tissue inflammation and HIV incidence [38]. Genital schistosomiasis has been associated with female infertility [39].

Issues related to schistosomiasis and glomerular disease are discussed separately. (See "Schistosomiasis and glomerular disease".)

Hepatosplenic schistosomiasis — Hepatosplenic schistosomiasis associated with intestinal schistosomiasis can cause severe portal hypertension and gastrointestinal bleeding. Repeated mass treatment with praziquantel has substantially reduced both splenomegaly and hepatic fibrosis especially in younger patients [36]. In adult patients with established hepatic fibrosis with portal hypertension, variceal bleeding is the most common complication. Treatment options include surgical portosystemic shunt or esophagogastric devascularization with splenectomy, and medical treatment with beta-blockers [40]; the optimal approach is uncertain [41-44]. In one case series including 45 patients with hepatosplenic schistosomiasis who underwent splenectomy, reduction in portal hypertension and improvement in coagulation factors and liver function tests were observed [41].

Hepatosplenic schistosomiasis is associated with glomerular dysfunction. Patients with hepatosplenic schistosomiasis living in endemic regions warrant annual screening for glomerular disease and renal dysfunction via measurement of serum creatinine and urine dipstick testing (to evaluate for presence of proteinuria and/or hematuria) [45]. If an abnormal urine dipstick result is observed, the urine sediment should be examined, and proteinuria should be quantified with a urine protein-to-creatinine ratio.

Issues related to schistosomiasis and glomerular disease are discussed separately. (See "Schistosomiasis and glomerular disease".)

Neuroschistosomiasis — Neuroschistosomiasis develops as a result of embolization of adult worms to the spinal cord or cerebral microcirculation, with subsequent release of eggs leading to an intense inflammatory reaction with local tissue destruction and scarring. It can cause cerebral disease or myelopathy; the latter is more common. Clinical manifestations are discussed further separately. (See "Schistosomiasis: Epidemiology and clinical manifestations", section on 'Neuroschistosomiasis'.)

Prompt corticosteroid treatment (prednisone 1 to 2 mg/kg per day) is essential to limit irreversible tissue damage that occurs as a result of the intense inflammatory response mainly towards the embolized eggs [46-48]. If the diagnosis of neuroschistosomiasis is suspected but not proven, corticosteroid therapy should be administered, nonetheless. The approach to diagnosis is discussed separately. (See "Schistosomiasis: Diagnosis", section on 'Neuroschistosomiasis'.)

The duration of corticosteroid therapy is uncertain; in general, treatment should be continued for several months but could be tapered off gradually, tailored to individual circumstances. Premature interruption or tapering off steroid dosage too quickly may result in clinical relapse [49]. In one study including 16 patients with myeloradiculopathy due to neuroschistosomiasis, the best clinical outcome was achieved among patients who received steroid treatment for at least two months [50]. In the setting of prolonged corticosteroid use, concomitant infection with Strongyloides should be excluded or treated to prevent the syndrome of strongyloidiasis hyperinfection. (See "Strongyloidiasis".)

Praziquantel (40 mg/kg single dose) can provoke an inflammatory response with paradoxical worsening of neurologic symptoms and should therefore be administered a few days after initiation of corticosteroid treatment [51-53]. Praziquantel may be sufficient for elimination of adult worms and halting egg production, but it does not inactivate eggs embedded at ectopic sites, hence the need for prolonged corticosteroid treatment [54]. In neuroschistosomiasis, repeated doses of praziquantel (40 to 60 mg/kg per day for 3 days) are often given, but the added benefit is uncertain [49]. In the setting of associated seizures, anticonvulsant therapy should be administered. (See "Overview of the management of epilepsy in adults", section on 'Antiseizure medication therapy'.)

Anthelminthic therapy

Praziquantel — Praziquantel alters the tegument structure of adult worms and increases calcium ion permeability. Calcium ions accumulate in the cytosol, leading to muscular contractions and subsequent paralysis. Damage to the tegument membrane also induces a host immune response to parasite antigens [55]. Therefore, the efficacy of praziquantel depends on both the parasite burden of infection and the host immune defense [56].

Praziquantel is readily absorbed when taken orally with food and has a short plasma half-life [17]. Adverse effects of praziquantel occur in approximately one-third of patients and are generally mild. They include dizziness, headache, vomiting, abdominal pain, diarrhea, and pruritus. These symptoms may be attributable to the drug itself and/or to the host immune response to dying parasites. Therefore, adverse effects may be observed more frequently among patients with high parasite burden [57]. Paradoxical hypersensitivity reactions following treatment with praziquantel may be observed among travelers with acute infection and/or in the setting of early chronic schistosomiasis [9,11,57].

Praziquantel may be used in pregnancy [58-62]. One trial including 370 pregnant women randomized to receive praziquantel or placebo noted no significant differences in safety outcomes including abortion, fetal death in utero, and congenital abnormalities [62]. Praziquantel is excreted in human breast milk, although no adverse effects during lactation have been reported; most favor discontinuation of breastfeeding at the time of treatment and for 72 hours thereafter or delaying treatment until after breastfeeding.

Drug resistance — True resistance to praziquantel remains exceptional, despite its extensive use in endemic regions for many years [18]. Praziquantel probably acts on multiple pharmacologically relevant targets, with a combined detrimental effect on the parasite [63]. Schistosome species with reduced sensitivity to praziquantel in vivo and in vitro have been described [57,64-69]; it is unclear if these observations represent resistance or reinfection. In addition, the distinction between worm burden reduction and failure to eradicate infection in these reports is not always clear.

In a region of S. mansoni transmission in Senegal, praziquantel was curative among only 35 percent of individuals; this may be related to high parasite burden and intense transmission with rapid reinfection [65,66]. Another report noted that S. mansoni parasites demonstrated reduced killing upon exposure to praziquantel in vitro [69]. Therapeutic failure has also been reported in travelers [67,68,70,71].

Alternative therapies — Oxamniquine is occasionally used for refractory S. mansoni infection. It is contraindicated in pregnancy and is not as effective as praziquantel [72,73]. Research is ongoing to develop derivatives of oxamniquine as a broad-spectrum anti-schistosome treatment [74]. Artemisinin derivatives act on the glucose metabolism of immature schistosomes [75] and could be of use in very early infection [8]. The concentration of praziquantel may be increased by coadministration of dihydroartemisinin-piperaquine [76], and a trial has demonstrated that combination therapy with these drugs is more effective than praziquantel alone [77]. Mefloquine has limited action on mature worms. The addition of mefloquine or artesunate to praziquantel is of limited value [78,79].

CONTROL AND PREVENTION — Schistosomiasis control strategies for endemic areas include periodic mass treatment, water sanitation programs, and vaccine development. In areas with intense transmission, the principal objectives of control programs include infection control and reduction of schistosome morbidity. The association between parasite burden and morbidity is species specific; it is much more pronounced in S. haematobium infection than in S. mansoni infection [80].

The main control activity advocated by the World Health Organization (WHO) consists of periodic mass drug administration, which reduces the adult worm burden and ensuing morbidity; this approach also reduces the intensity of reinfection over time [81-86]. Periodic mass treatment is particularly beneficial among school age children, who usually carry the highest parasite burden. Repeated treatment accelerates immunologic resistance against reinfection in this age group, significantly reducing morbidity.

The approach to mass treatment consists of praziquantel administration (single dose 40 mg/kg orally) to school children and adults (including pregnant women). Most treatment programs are school centered; preschool children are less affected and praziquantel is relatively contraindicated for toddlers <4 years.

Praziquantel treatment is given on an annual or biannual basis depending on regional species and transmission intensity [59,60,87]. In one study including more than 12,000 children with urinary schistosomiasis in Cote d'Ivoire, the prevalence of S. haematobium was lower among those who received biannual treatment rather than annual treatment (0.6 versus 7.5 percent); however, interruption of transmission was not achieved [88].

Annual mass drug administration is appropriate for disease control in most settings. In some settings, multiple rounds of mass praziquantel administration have been associated with diminished efficacy, particularly in regions with high endemicity levels [89]. However, there is no clear evidence for emergence of praziquantel resistance. In a 2022 treatment guideline, the WHO recommended to treat a larger section of the population more frequently, even in lower schistosome prevalence settings [90].

Praziquantel kills adult larvae but does not kill eggs or immature worms that may sustain transmission in between treatment rounds. [8,9]. As an example, in a systematic review of multiyear data from control programs implementing mass praziquantel administration as the key intervention strategy in several countries (Mali, Niger, Burkina Faso, Rwanda, Uganda, Burundi, Tanzania, Malawi, and Yemen), a reduction in prevalence of heavy-intensity S. mansoni and S. haematobium infection among school-age children to <5 percent was observed in all countries except Niger [91]. Elimination (reduction in prevalence to <1 percent) was achieved in half of the countries, for S. mansoni infection only. Sustained control of schistosomiasis requires repeated therapeutic intervention and concerted action to eliminate transmission at the long run. In many settings with high transmission rates, periodic mass drug administration alone may not be sufficient to eradicate schistosomiasis infection; additional measures are needed [92-94]. These include environmental measures targeting the transmission dynamics by (1) interfering with the biology of the intermediate host and (2) reducing the risk of reinfection from water sources. In some regions with less intense or more focal transmission, combining these measures may render eradication feasible. More precise diagnostics may be needed to achieve eradication [23]. These and other measures have facilitated eradication of schistosomiasis in Japan and have been adopted as a national strategy in China [92,94,95].

Minimizing contact with fresh water containing infectious cercarial larvae is an important control measure. Interventions include provision of safe water supplies with proper sewage control and community education regarding wearing protective clothing and footwear in the setting of freshwater exposure [96]. Other measures include vigorous toweling of exposed skin and/or applying insect repellent DEET (N,N-diethyl-m-toluamide) following fresh water exposure [97]. Eradication of snail species via molluscicides (eg, niclosamide, copper sulphate) or control of snail breeding sites has been attempted, although such measures difficult to sustain because repopulation can occur rapidly and because of downstream environmental effects [96,98].

Vaccination could play a significant role in resistance to infection. Vaccines may alter the outcome of schistosomiasis infection by acting upon the delicate interplay between T helper cell reactions (Th1 and Th2) directed towards schistosome egg antigens embedded in tissues. Vaccines targeting the invasive stage (cercariae, schistosomules) may increase resistance to infection. Several schistosome antigens have been identified as vaccine candidates, and various vaccine platforms have been considered [99,100]. Others have been extensively tested in animal models of zoonotic schistosomiasis (S. japonicum) with variable results. The S. mansoni controlled human infection (CHI-S) model offers an exciting platform to test schistosome vaccine candidates in humans [101-105].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Schistosomiasis".)

SUMMARY AND RECOMMENDATIONS

●Treatment of schistosomiasis serves three purposes: reversing acute or early chronic disease, preventing complications associated with chronic infection, and preventing neuroschistosomiasis. The goal of treatment is reduction of egg production via reduction of worm load. (See 'Treatment' above.)

●For patients with acute schistosomiasis syndrome, our approach consists of initial management with corticosteroids to reduce inflammation. Thereafter, we suggest administration of praziquantel 8 to 12 weeks after infection (together with prednisolone), followed by repeat praziquantel treatment 4 to 6 weeks later (without corticosteroids) (Grade 2C). Corticosteroids are given with initial treatment because administration of praziquantel within 12 weeks following infection may be associated with aggravation of symptoms (See 'Acute schistosomiasis syndrome' above.)

●For patients with chronic infection, we suggest treatment with praziquantel (single dose) (Grade 2C). Dosing of praziquantel for treatment of infection due to Schistosoma haematobium, Schistosoma mansoni, or Schistosoma intercalatum consists of 40 mg/kg (in one or two divided doses). Praziquantel dosing for treatment of infection due to Schistosoma japonicum or Schistosoma mekongi consists of 60 mg/kg (in two divided doses). (See 'Clinical approach' above.)

●Follow-up after treatment includes monitoring of clinical manifestations, eosinophilia, and microscopy evaluation for eggs in stool or urine. In endemic areas, follow-up microscopy should be performed no sooner than six weeks following treatment. In nonendemic areas, follow-up microscopy may be performed three to six months after treatment. Persistence of viable eggs after treatment with praziquantel warrants repeat treatment. (See 'Clinical approach' above.)

●Treatment of neuroschistosomiasis consists of prompt and sustained corticosteroid treatment. Praziquantel should be administered a few days after initiation of corticosteroid treatment; the two therapies should be given concomitantly. (See 'Neuroschistosomiasis' above.)

●Schistosomiasis control strategies for endemic areas include mass treatment and water sanitation programs. (See 'Control and prevention' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Karin Leder, MD, and Peter Weller, MD, who contributed to an earlier version of this topic.