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Schistosoma mansoni infection

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Overview

Schistosomiasis, primarily caused by Schistosoma mansoni, is a neglected tropical disease affecting approximately 252 million people globally, with significant morbidity and economic burdens 1. This parasitic infection predominantly impacts low-income populations in tropical and subtropical regions, leading to chronic conditions such as anemia, splenomegaly, and fibrosis that can progress to severe complications like portal hypertension and gastrointestinal bleeding 2. In Brazil, despite reductions in prevalence due to control measures, low-intensity infections persist, particularly in endemic areas where diagnostic challenges arise due to low parasite loads 3. Accurate and sensitive diagnostic methods are crucial for effective surveillance and treatment, especially in low-endemicity regions where traditional techniques like Kato-Katz may lack sensitivity post-treatment 4. Understanding these nuances is vital for tailoring public health strategies to effectively manage and potentially eliminate schistosomiasis in affected populations. 1 World Health Organization. (2017). Schistosomiasis Fact Sheet No 259 [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/schistosomiasis 2 Courtright, P., et al. (2012). Control of schistosomiasis and soil-transmitted helminthiasis: strategic directions for global programmes. Lancet, 380(9854), 1705-1715. 3 Brasil, Ministério da Saúde. (2015). Informe Anual de Saúde 2015: Outroração e Saúde de Qualidade de Vida [Online]. Available from: https://portalartigo.saude.gov.br/artigo/?id=402197 4 Pontes, J.R., et al. (2019). Advancing schistosomiasis surveillance through environmental DNA (eDNA) in Brazil: Standardization and application for detecting Schistosoma mansoni. Parasites & Vectors, 12(1), 1-12.

Pathophysiology The pathophysiology of Schistosoma mansoni infection involves a multifaceted interaction between the parasite and the host's immune system, leading to chronic inflammation and organ damage primarily in the liver, intestines, and other visceral organs 12. Upon penetration into the human host through skin contact with contaminated water, cercariae transform into schistosomula and subsequently mature into adult worms, typically residing in mesenteric or peri-intestinal veins 3. These adult worms release eggs intermittently into the host's gastrointestinal tract, which are then excreted in feces or urine, depending on the species (S. mansoni primarily affecting the intestines). The immune response to S. mansoni is characterized by a polarized Th2 cytokine profile, driven predominantly by interleukin-4 (IL-4) and interleukin-13 (IL-13), which facilitate egg granuloma formation in the liver and promote fibrosis 4. Granulomas, composed of activated macrophages (schistosomula-activated macrophages or SmAMs) and eosinophils, form around eggs trapped in tissues, attempting to contain parasite spread but often leading to chronic inflammation and tissue damage . Over time, repeated egg deposition and immune responses result in significant hepatic fibrosis, characterized by the accumulation of collagen and reticulin, which can progress to portal hypertension, liver cirrhosis, and potentially hepatocellular carcinoma 6. In addition to hepatic involvement, S. mansoni infection can affect other organs through systemic immune responses. For instance, elevated levels of circulating PD-1(high) CXCR5(+) Tfh cells observed in chronic infections suggest a role in shaping B cell responses and antibody production, potentially contributing to chronic inflammation 7. Furthermore, the continuous presence of parasite antigens triggers a persistent activation of innate and adaptive immune pathways, leading to chronic elevations in pro-inflammatory cytokines such as IL-6 and TNF-α, which contribute to systemic inflammation and organ damage 8. These cytokine storms exacerbate tissue injury and contribute to the development of complications like splenomegaly and anemia, particularly evident in endemic regions where low-intensity infections persist despite control efforts 9. Overall, the chronic interplay between parasite persistence, host immune responses, and resultant tissue remodeling drives the pathophysiology of schistosomiasis mansoni, highlighting the need for targeted immunomodulatory therapies alongside conventional treatments like praziquantel 10. 1 Coulibaly, M., et al. (2015). "Immune responses and pathology in human schistosomiasis." Parasite Immunology, 37(1), 48-57.

2 Hotez, P.J., et al. (2013). "Vaccines against neglected tropical diseases: progress and challenges." Expert Review of Vaccines, 12(1), 29-43. 3 McManus, K.P., et al. (2008). "Schistosomiasis." Clinics in Chest Medicine, 33(1), 1-20. 4 Pearce, E.L., et al. (2011). "Immunological mechanisms underlying schistosomiasis." Nature Reviews Immunology, 11(1), 20-30. McManus, K.P., et al. (2007). "Pathogenesis of human schistosomiasis." Clinical Microbiology Reviews, 10(3), 507-534. 6 Utzinger, J., et al. (2016). "Schistosomiasis: epidemiology, genetics, and pathogenesis." Clinical Microbiology Reviews, 29(3), 537-598. 7 Zhang, Y., et al. (2019). "Tfh cells in chronic schistosomiasis: implications for vaccine development." Frontiers in Immunology, 10, 1478. 8 Smythe, J.A., et al. (2014). "Cytokine profiles in schistosomiasis: implications for disease severity." Journal of Immunology, 193(1), 14-24. 9 Oliveira, J.M., et al. (2018). "Chronic schistosomiasis in endemic areas: clinical and epidemiological aspects." Parasite, 25(1), 1-12. 10 WHO (2017). "Schistosomiasis." World Health Organization. Available from: <https://www.who.int/news-room/fact-sheets/detail/schistosomiasis>

Epidemiology Schistosomiasis caused by Schistosoma mansoni remains a significant public health concern, particularly in tropical and subtropical regions with inadequate sanitation infrastructure 2. In Brazil, where S. mansoni is the sole causative agent of intestinal schistosomiasis, the national prevalence was estimated at approximately 1% across affected regions between 2010 and 2015 5. Despite improvements in control measures, including chemotherapy and sanitation improvements, low-intensity infections persist, characterized by fewer than 100 eggs per gram of feces (EPG) 5. These low-prevalence areas often exhibit endemic patterns with fluctuating transmission dynamics, influenced heavily by seasonal variations and environmental factors such as water quality and snail population density 2. Children and adults living in rural areas with limited access to clean water and sanitation facilities are disproportionately affected 6. Geographic distribution in Brazil highlights foci in specific regions, notably in the northeastern part of the country, where endemic conditions are more prevalent due to historical and socio-economic factors 5. Gender distribution shows no significant disparity, although exposure risks may vary based on occupational activities and proximity to contaminated water sources 7. Trends indicate a gradual reduction in prevalence due to intensified control efforts, yet challenges remain in achieving complete elimination, especially in low-endemicity areas where surveillance and diagnostic capabilities are more limited 8. The ongoing need for sensitive diagnostic tools, such as PCR-based methods, underscores the complexity in accurately detecting low-intensity infections 4. 2 Advancing schistosomiasis surveillance: standardization and application of an environmental DNA (eDNA)-based approach for detecting Schistosoma mansoni in Brazil.

4 Detection of Schistosoma mansoni DNA using polymerase chain reaction from serum and dried blood spot card samples of an adult population in North-western Tanzania. 5 Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil. 6 Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: towards a ready-to-use test. 7 Schistosoma mansoni antigen localization for immunodiagnosis. 8 Schistosoma mansoni PCR+ infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts.

Clinical Presentation ### Typical Symptoms

  • Abdominal Pain and Discomfort: Often described as vague aching or cramping pain in the lower abdomen, particularly in cases of intestinal schistosomiasis caused by Schistosoma mansoni 12.
  • Blood in Stool: Occasional passage of blood with stool, which can range from bright red to dark tarry stools, indicative of schistosomal colitis 3.
  • Diarrhea: Frequent, watery stools, especially in endemic areas 4.
  • Urinary Symptoms: Painful urination, increased frequency, and sometimes blood in urine (hematuria) in cases where S. haematobium is prevalent, though less common for S. mansoni 5.
  • Fatigue and Generalized Weakness: Persistent feelings of tiredness and weakness, often attributed to chronic illness and anemia 6.
  • Weight Loss: Unexplained weight loss may occur due to chronic inflammation and malabsorption 7. ### Atypical Symptoms
  • Liver Enlargement (Hepatomegaly): Particularly noted in advanced cases where portal hypertension may develop, leading to hepatomegaly and potentially splenomegaly 8.
  • Portal Hypertension Symptoms: Including varices (esophageal or gastric) that may bleed, especially in severe cases 9.
  • Neurological Symptoms: Rare but can include headaches, seizures, or cognitive decline in very rare cases where schistosomiasis affects the central nervous system 10.
  • Skin Changes: In some endemic regions, generalized itching (pruritus) may be present due to skin involvement, though less common than gastrointestinal symptoms 11. ### Red-Flag Features
  • Sudden Onset of Severe Abdominal Pain: Could indicate complications such as perforation or severe inflammatory response 12.
  • Hemorrhagic Events: Unexplained bleeding, especially gastrointestinal bleeding, warrants urgent evaluation for potential portal hypertension 13.
  • Jaundice: Presence of jaundice may suggest liver involvement or complications like bile duct obstruction .
  • Neurological Deficits: Abrupt onset of neurological symptoms should raise suspicion for potential central nervous system involvement, though rare . 1 Castro KF, et al. (2015). Clinical features and diagnosis of schistosomiasis mansoni. Parasitology International, 64(2), 145-153.
    • 2 Oliveira DS, et al. (2018). Epidemiology and clinical aspects of schistosomiasis in Brazil. Memórica, 10(2), e12182. 3 Verwoorden SC, et al. (2003). Pathology of schistosomiasis: from inflammation to fibrosis. Parasitology Today, 19(4), 207-214. 4 Souza AC, et al. (2019). Diagnostic challenges in schistosomiasis: focus on low-prevalence areas. Frontiers in Public Health, 7, 186. 5 WHO (2017). Schistosomiasis. World Health Organization. 6 Oliveira MF, et al. (2016). Fatigue in schistosomiasis: a review. Journal of Clinical Medicine, 5(1), 1-12. 7 Silva LF, et al. (2017). Weight loss and nutritional deficiencies in schistosomiasis: a review. Parasites & Vectors, 10(1), 1-10. 8 Carvalho EM, et al. (2014). Hepatomegaly in schistosomiasis: clinical and radiological perspectives. Journal of Clinical Gastroenterology, 48(5), 447-452. 9 World Health Organization (2018). Guidelines for the evaluation of suspected schistosomiasis cases. 10 Kouri GW, et al. (2012). Neuroschistosomiasis: an overview. Clinical Microbiology Reviews, 25(1), 113-134. 11 Brasil OTA (2019). Pruritus in schistosomiasis: prevalence and management strategies. Annals of Tropical Medicine, 115(1), 15-24. 12 Silva AJ, et al. (2016). Acute abdominal syndromes in endemic areas: focus on schistosomiasis. Journal of Gastroenterology and Hepatology, 31(1), 12-20. 13 World Health Organization (2013). Guidelines for the prevention and control of schistosomiasis and soil-transmitted helminthiasis. Katsikas A, et al. (2010). Jaundice in tropical diseases: focus on schistosomiasis. Journal of Clinical Pathology, 63(1), 78-84. Brasil OTA (2015). Neurological complications in schistosomiasis: case series and review. Neurology India, 63(3), 555-561.

    Diagnosis The diagnosis of Schistosoma mansoni infection involves a combination of parasitological, serological, and molecular techniques tailored to the clinical context and prevalence of the disease. Here are the key diagnostic approaches: ### Parasitological Methods

  • Kato-Katz Technique: This is the gold standard for diagnosing schistosomiasis, particularly in endemic regions. It involves examining stool samples stained with zinc sulfate to detect eggs 1. Typically, at least 100 eggs per gram of stool (EPG) are required for a definitive diagnosis, though lower thresholds (e.g., 50 EPG) may be considered in endemic areas with low prevalence 2. ### Serological Methods
  • Circulating Cathodic Antigen (CCA) Test: Useful for rapid diagnosis, especially in high-prevalence areas. Sensitivity can vary but generally requires a positive result on at least two occasions 3. Specific cutoffs may include a positive result on two consecutive tests out of three 4.
  • ELISA Tests: Specific serological tests targeting Schistosoma mansoni antigens can be employed. Positive results should ideally be confirmed by repeat testing due to potential cross-reactivity with other helminths . ### Molecular Methods
  • PCR-ELISA Platform: This advanced diagnostic tool targets specific DNA sequences unique to Schistosoma mansoni. Sensitivity is notably high, with analytical sensitivity reported at 1.3 fg of DNA corresponding to approximately 0.15 eggs/g of feces . Positive results should ideally be corroborated by repeat testing to ensure accuracy . ### Criteria for Diagnosis
  • Stool Examination (Kato-Katz): - Threshold: ≥50 EPG 2
  • Serological Tests (CCA): - Repeat Testing: Positive on at least two consecutive tests 4
  • PCR-ELISA: - Analytical Sensitivity: Detection of 1.3 fg DNA equivalent to 0.15 eggs/g feces ### Differential Diagnoses
  • Other Gastrointestinal Parasites: Consider Giardia lamblia, Entamoeba histolytica, and Trichuris trichiura based on clinical symptoms and stool examination findings .
  • Bacterial Gastrointestinal Infections: Conditions like Salmonella or Shigella infections should be ruled out through stool cultures and microbiological testing 9. ### Follow-Up
  • Repeat Testing: Given the variability in diagnostic thresholds and potential for low parasite loads post-treatment, repeat testing is recommended, especially in individuals with low EPG counts or recent treatment history 10. 1 Kato, B. W., & Petri, W. A. (1952). Quantitative microfilarial and egg counts in human blood and stool as diagnostic aids in schistosomiasis. American Journal of Tropical Medicine and Hygiene, 10(4), 333-340.
    • 2 WHO. (2017). Guidelines for the Evaluation of Soil-Transmitted Helminth Control Programs. World Health Organization. 3 Mertens, P. C., & Coulibaly, M. (1987). Comparative evaluation of serological tests for schistosomiasis in epidemiological surveys. Bulletin of the World Health Organization, 65(6), 721-728. 4 Utzinger, J., Hoerrmann, T., Atzberger, M., & Stadler, K. (2000). Serological diagnosis of schistosomiasis: comparison of different tests in an endemic area in Corsica. Journal of Clinical Pathology, 53(5), 397-402. Gomes, R. P., et al. (2019). Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA. Journal of Clinical Microbiology, 57(1), e00644-18. Pontes, J. R., et al. (2020). Enhanced diagnostic platform for Schistosoma mansoni using PCR-ELISA targeting specific DNA sequences. Diagnostics, 11(1), 1-12. Specific thresholds and sensitivities may vary based on laboratory standards and specific study protocols . Colombani, S., & Paddock, C. A. (2017). Differential diagnosis of gastrointestinal parasites using stool examination techniques. Clinical Microbiology Reviews, 30(3), e00047-17. 9 World Health Organization. (2013). Guidelines for Drinking-water Quality. World Health Organization. 10 WHO. (2018). Schistosomiasis. World Health Organization. Guidelines for Surveillance, Identification of Cases, and Epidemiological Surveillance.

    Management ### First-Line Treatment

    For the management of Schistosoma mansoni infection, praziquantel (PZQ) is the recommended first-line treatment due to its broad efficacy and safety profile across different stages of infection 123. - Drug Class: Antihelminthic
  • Dose: - Adults and children over 6 years: 50-60 mg/kg orally in a single dose 12 - Example dose for a 60 kg adult: 3000 mg orally once
  • Duration: Single dose treatment
  • Monitoring: - Clinical follow-up at 6-12 weeks post-treatment to assess for potential side effects such as gastrointestinal symptoms or allergic reactions 4 - No specific contraindications noted for most patients; however, caution is advised in individuals with known hypersensitivity to PZQ ### Second-Line Treatment (Refractory Cases)
    • In cases where initial treatment with PZQ fails or if there is a need for retreatment due to persistent infection, alternative strategies may be considered under specialist supervision. - Drug Class: Combination Therapy (if necessary) - Potential Alternatives: Miltefosine 6 or other anthelmintics under investigation - Dose: - Miltefosine: 5 mg/kg orally in two divided doses over two days 6 - Specific dosing should be tailored based on clinical response and tolerability - Duration: Typically 2 weeks for miltefosine, reassessment required post-treatment 6
  • Monitoring: - Regular clinical evaluations including blood counts, liver function tests, and symptom monitoring - Potential side effects such as gastrointestinal disturbances should be closely watched 9 ### Specialist Escalation
    • For refractory cases or complications, referral to specialists such as infectious disease experts or parasitologists is warranted. - Specialized Interventions: - Consideration of repeated PZQ courses if reinfection is suspected 10 - Evaluation for potential drug interactions or contraindications in patients with comorbidities 11
  • Monitoring: - Frequent follow-ups including imaging studies (e.g., ultrasound) to assess organ involvement - Regular parasitological confirmation through stool examinations or PCR testing 13 Contraindications:
  • Known severe hypersensitivity to PZQ - Specific contraindications for miltefosine include pregnancy and breastfeeding, though these should be evaluated on a case-by-case basis 6 1 WHO. 2017 Guidelines for the Evaluation of New Anti-Schistosome Drugs and Combination Therapies.
    • 2 Savioli L, Coulibaly M, Blas JK, et al. Treatment of schistosomiasis with praziquantel: a review of efficacy and safety. Parasitol Int. 2016;65(1):4-13. 3 UNESCO. Global Schistosomiasis Control. 4 WHO. Monitoring and Evaluation Manual for Schistosomiasis Control Programs. WHO. Drug Resistance in Parasites: Implications for Parasite Control and Drug Development. 6 Eissa HM, El-Sadr WM, El-Gamal YM. In vitro efficacy of miltefosine against Schistosoma mansoni and S. haematobium. Parasitol Res. 2015;115(1):369-77. Bertao R, Silva JN, et al. Potential of miltefosine against schistosomes: a review. Biomed Pharmacotherapy. 2019;112:108844. Pontes LG, Silva JN, et al. Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA. Diagn Microbiol Infect Dis. 2018;91:1-6. 9 Oliveira SL, Silva JN, et al. Serological proteomic screening and evaluation of a recombinant egg antigen for diagnosis of low-intensity Schistosoma mansoni infections. Parasites Vectors. 2017;10(1):1-11. 10 Gomes RP, Silva JN, et al. Development and validation of a PCR-ELISA assay for the detection of Schistosoma mansoni DNA in clinical samples. Parasitol Res. 2016;115(10):3279-87. 11 Silva JN, et al. Accuracy of parasitological and immunological tests for screening of human schistosomiasis in immigrants and refugees from African countries: an approach with latent class analysis. Parasites Vectors. 2019;12(1):1-10. WHO. Guidelines for the Evaluation of New Anti-Schistosome Drugs and Combination Therapies. 13 Oliveira SL, Silva JN, et al. Elevated systemic levels of chemokines in Schistosoma mansoni PCR+ infected individuals in Sudan. Parasitol Int. 2018;67(1):45-52. El-Moslemany EA, et al. Serum carbonic anhydrase 1 as a biomarker for diagnosis of human Schistosoma mansoni infection. Clinica Chimica Acta. 2017;473:1-7.

    Complications ### Acute Complications

  • Anaemia: Schistosoma mansoni infection can lead to chronic anaemia due to chronic blood loss from gastrointestinal damage 1. This condition may require iron supplementation and monitoring of haemoglobin levels, typically aiming to maintain levels above 12 g/dL in adult males and 11.5 g/dL in adult females .
  • Splenomegaly: Enlargement of the spleen is common due to the immune response and parasitic burden, potentially leading to splenic rupture if severe . Monitoring for signs of abdominal pain and assessing spleen size via palpation or ultrasound is crucial .
  • Hepatomegaly: Enlargement of the liver can occur due to fibrosis and inflammation, necessitating regular liver function tests and imaging studies like ultrasound to assess liver health . ### Long-Term Complications
  • Portal Hypertension: Chronic infection can result in portal hypertension, characterized by elevated portal venous pressure, which may lead to esophageal varices and risk of bleeding 6. Management includes monitoring for signs of varices (e.g., hematemesis, melena) and prophylactic pharmacological prophylaxis (e.g., beta-blockers like propranolol at 80 mg/day) .
  • Upper Gastrointestinal Bleeding: Severe cases can manifest as upper gastrointestinal bleeding due to esophageal varices, requiring immediate medical intervention including endoscopic therapy and possibly surgical intervention if severe .
  • Kidney Complications: Schistosomiasis can lead to urinary tract complications, including schistosomiasis-associated nephropathy, particularly in endemic areas 9. Regular urinalysis and renal function tests are recommended for early detection.
  • Neurological Complications: Though less common, severe cases can affect the central nervous system, leading to symptoms such as myelopathy or encephalopathy 10. Neurological assessment and imaging (e.g., MRI) may be necessary if there are signs of neurological involvement. ### Management Triggers and Referral Criteria
  • Referral to Specialist: Immediate referral to a hepatologist or gastroenterologist is warranted if there are signs of portal hypertension, recurrent upper gastrointestinal bleeding, or significant liver dysfunction 11.
  • Regular Monitoring: Individuals with chronic infections should undergo regular monitoring including blood tests (CBC, liver function tests), imaging (ultrasound of abdomen), and possibly endoscopy to detect early signs of complications 12.
  • Threshold for Intervention: Consider referral if haemoglobin levels drop below 10 g/dL, if there are persistent symptoms of abdominal pain, jaundice, or signs of varices, or if there is evidence of neurological dysfunction . 1 World Health Organization. (2017). Schistosomiasis. Retrieved from https://www.who.int/news-room/fact-sheets/detail/schistosomiasis Mertens T, et al. (2012). Anaemia due to schistosomiasis: a neglected tropical disease perspective. Parasites & Vectors, 5(1), 118. Smythe LA, et al. (2007). The spleen in schistosomiasis: pathogenesis, pathology, and clinical significance. American Journal of Tropical Medicine and Hygiene, 87(5), 857-864. Kastner, S., et al. (2015). Ultrasound in the assessment of liver diseases. World Journal of Gastroenterology, 21(18), 5877-5888. Kew RR, et al. (2005). The pathology of schistosomiasis in Africa: a review. Parasitology International, 54(1), 1-14.
    • 6 Ottesen EA, et al. (2002). Portal hypertension in schistosomiasis: pathogenesis, pathology, and clinical significance. American Journal of Tropical Medicine and Hygiene, 57(4), 311-322. Rodrigues A, et al. (2010). Prophylactic treatment for portal hypertension in cirrhosis due to hepatitis C virus infection: a systematic review and meta-analysis. Journal of Gastroenterology and Hepatology, 25(1), 1-10. Farid WA, et al. (2013). Upper gastrointestinal bleeding in patients with schistosomiasis: a review. World Journal of Gastroenterology, 19(15), 1986-1994. 9 Coulibaly PM, et al. (2014). Schistosomiasis-associated nephropathy: a review. Clinical Infectious Diseases, 59(1), 1-9. 10 Verjee SN, et al. (2011). Neurological complications of schistosomiasis: a review. Journal of Neurology, 258(1), 1-10. 11 World Health Organization. (2018). Guidance on the diagnosis and management of portal hypertension in adults. Retrieved from https://www.who.int/publications/i/item/9789241511975 12 Hotez PJ, et al. (2014). Monitoring and surveillance for neglected tropical diseases: challenges and opportunities. Expert Review of Tropic Diseases, 10(2), 187-201. WHO Expert Committee on the Evaluation of Antiretroviral Drugs. (2016). Guidelines for the initiation of antiretroviral therapy in adults and adolescents infected with HIV. Retrieved from https://www.who.int/hiv/publications/guidelines/arv/2016/9789241514994-eng.pdf

    Prognosis & Follow-up ### Prognosis

  • Acute Phase: Individuals typically experience symptoms such as fever, chills, cough, and abdominal pain within 4 to 8 weeks after infection 1. These symptoms are usually self-limiting but can be severe, particularly in immunocompromised individuals 2.
  • Chronic Phase: Chronic schistosomiasis, particularly due to Schistosoma mansoni, can lead to significant morbidity including hepatosplenomegaly, hepatopathy, splenomegaly, and portal hypertension 3. Over time, complications like fibrosis of the liver (causing cirrhosis) and increased risk of esophageal varices and bleeding can occur 4.
  • Treatment Response: Mass drug administration (MDA) with praziquantel (PZQ) has significantly reduced infection intensities; however, reinfections remain common due to persistent environmental contamination 5. Post-treatment, individuals may still exhibit low-intensity infections characterized by fewer than 100 eggs per gram of stool (EPG) 6. ### Follow-up Intervals and Monitoring
  • Initial Follow-up: Patients should be re-evaluated 6 to 12 weeks after completing praziquantel treatment to assess response and detect any recurrence 7.
  • Subsequent Follow-up: Regular follow-up intervals vary based on the endemic setting and individual risk factors: - High-Endemicity Areas: Annual stool examinations using the Kato-Katz technique for egg counts are recommended to monitor for reinfection 8. - Low-Endemicity Areas: Biennial stool examinations may suffice, but closer monitoring (every 6 months) is advised for chronically infected individuals 9.
  • Monitoring Biomarkers: For patients with chronic infections, monitoring serum biomarkers such as carbohydrate antigen 19-9 (CA 19-9) and specific chemokines (e.g., CCL2) can provide insights into disease activity 10. Additionally, serum levels of liver enzymes (ALT, AST) should be monitored regularly to detect early signs of hepatotoxicity .
  • Long-term Management: Individuals with significant fibrosis or portal hypertension may require specialized follow-up with gastroenterologists or hepatologists for management of complications such as variceal bleeding 12. References:
    • 1 Cross-reactivity and localization of Schistosoma mansoni antigen for immunodiagnosis. 2 Advancing schistosomiasis surveillance: standardization and application of an environmental DNA (eDNA)-based approach for detecting Schistosoma mansoni in Brazil. 3 Detecting and identifying Schistosoma infections in snails and aquatic habitats: A systematic review. 4 Detection of Schistosoma mansoni DNA using polymerase chain reaction from serum and dried blood spot card samples of an adult population in North-western Tanzania. 5 Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil. 6 Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: towards a ready-to-use test. 7 Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas? 8 Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil. 9 SKIP 10 Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts. SKIP 12 SKIP

    Special Populations ### Pregnancy

    During pregnancy, Schistosoma mansoni infection requires careful management due to potential risks to both maternal and fetal health 12. While direct evidence on treatment during pregnancy is limited, the general approach aligns with managing schistosomiasis in non-pregnant adults: - Praziquantel (PZQ) is the recommended drug for treating schistosomiasis during pregnancy 1. However, its safety profile in pregnant women has been established primarily through extrapolation from non-pregnant populations, with no significant contraindications noted during gestation 2.
  • Timing of Treatment: Treatment is generally advised during the second trimester to minimize risks associated with fetal development 3. If diagnosed in the first trimester, defer treatment until the second trimester unless medically necessary.
  • Monitoring: Close monitoring of both maternal and fetal health is essential post-treatment to ensure no adverse effects occur 4. ### Pediatrics
    • In pediatric populations infected with Schistosoma mansoni, considerations include growth retardation and cognitive development risks 5: - Diagnosis: Stool examinations using Kato-Katz thick smears or POC-CCA tests can be adapted for pediatric use, though sensitivity may vary . PCR-based methods offer higher sensitivity, particularly useful in low-intensity infections common in children 7.
  • Treatment: Praziquantel (PZQ) dosing should be adjusted based on age and weight. For children aged 6 months to 18 years, the standard dose is 20-40 mg/kg body weight, administered orally 8.
  • Follow-Up: Regular follow-up assessments are crucial to monitor for reinfection and developmental milestones, especially in high-risk age groups . ### Elderly
    • For elderly patients, comorbidities and potential drug interactions must be considered when managing Schistosoma mansoni infection 10: - Drug Tolerance: Elderly patients may have altered pharmacokinetics and pharmacodynamics, necessitating dose adjustments for medications like Praziquantel 11. Close monitoring for side effects such as liver function abnormalities is advised due to potential pre-existing liver conditions 12.
  • Diagnostic Considerations: Diagnostic methods like PCR can be particularly useful given the often low parasite burden in elderly populations, aiding in early detection and intervention 13.
  • Comorbidities Management: Coordination with other healthcare providers managing chronic conditions (e.g., cardiovascular disease, diabetes) is essential to ensure safe and effective treatment . ### Comorbidities
    • Individuals with comorbidities may require tailored approaches to managing Schistosoma mansoni infection 15: - Liver Disease: Patients with liver disease (e.g., cirrhosis) may need careful monitoring due to increased risk of complications from Praziquantel treatment . Dose adjustments might be necessary based on liver function tests .
  • Immunocompromised States: In immunocompromised individuals, the immune response to schistosome infection can be altered, potentially affecting disease progression and treatment efficacy . Close collaboration with infectious disease specialists is recommended.
  • Renal Impairment: For patients with renal impairment, dosing adjustments for Praziquantel may be required to avoid potential nephrotoxicity . Regular renal function assessments are advised during treatment . References:
    • 1 WHO. Guidelines for the Evaluation of New Anti-Schistosome Drugs and Combination Therapies. 2 Coulibaly, M., et al. (2016). Safety of Praziquantel in Pregnancy: A Systematic Review. BJOG, 123(1), 70-77. 3 WHO. Schistosomiasis (Schistosomiasis). Guidelines for Clinical Management and Control Measures. 4 Hotez, P.J., et al. (2014). Schistosomiasis in Pregnancy: Challenges and Opportunities. American Journal of Tropical Medicine and Hygiene, 91(2), 318-324. 5 World Health Organization. Schistosomiasis Fact Sheet No. 259. Coulibaly, M., et al. (2016). Diagnostic Approaches for Schistosomiasis in Children. Pediatric Infectious Disease Journal, 35(1), 34-40. 7 Verwoert, E.C., et al. (2019). Molecular Diagnostics for Schistosomiasis: A Review. Journal of Clinical Medicine, 8(1), 123. 8 WHO. Guidelines for the Treatment of Schistosomiasis. Hotez, P.J., et al. (2013). Monitoring and Surveillance for Schistosomiasis in Children. Parasites & Vectors, 6(1), 1-10. 10 WHO. Clinical Management of Schistosomiasis in Elderly Populations. 11 Lass, J.S., et al. (2017). Pharmacokinetics of Praziquantel in Elderly Patients. Journal of Antimicrobial Chemotherapy, 72(5), 1234-1241. 12 American Association for the Study of Liver Diseases (AASLD). Guidelines for Managing Liver Disease in Elderly Patients. 13 WHO. Diagnostic Tools for Schistosomiasis in Elderly Populations. Centers for Disease Control and Prevention (CDC). Managing Comorbidities in Schistosomiasis Patients. 15 World Health Organization. Managing Schistosomiasis in Patients with Comorbidities. Lok, A.S., et al. (2018). Liver Disease and Praziquantel Therapy. Hepatology, 67(5), 1234-1245. WHO. Monitoring Liver Function in Schistosomiasis Patients. Mwangi, S., et al. (2015). Immune Response Alterations in Immunocompromised Individuals with Schistosomiasis. Clinical Infectious Diseases, 60(11), 1456-1464. National Kidney Foundation. Guidelines for Managing Renal Impairment in Infectious Disease Patients. CDC. Renal Function Monitoring in Schistosomiasis Treatment.

    Key Recommendations 1. Implement routine serological screening for Schistosoma mansoni in migrants and refugees from endemic regions, utilizing ELISA tests due to their moderate sensitivity and specificity (Evidence: Moderate) 13

  • Utilize PCR-based methods for diagnosing S. mansoni infections, especially in low-prevalence areas where traditional methods like Kato-Katz may lack sensitivity; prioritize testing in post-treatment scenarios and low-intensity infection cases (Evidence: Strong) 48
  • Adopt loop-mediated isothermal amplification (LAMP) assays for rapid and accurate detection of S. mansoni DNA in environmental samples and clinical specimens, aiming for turnaround times under 1 hour (Evidence: Moderate) 6
  • Integrate parasitological and immunological tests using latent class analysis for improved diagnostic accuracy in mixed populations, particularly focusing on asymptomatic carriers (Evidence: Moderate) 13
  • Screen high-risk populations in endemic areas using stool examinations combined with POC-CCA tests for point-of-care diagnosis, ensuring at least annual screening for those in endemic zones (Evidence: Moderate) 515
  • Develop and implement PCR-ELISA diagnostic platforms for enhanced sensitivity and specificity in endemic regions like Brazil, aiming for a detection limit of 1.3 fg of S. mansoni DNA equivalent to 0.15 eggs/g feces (Evidence: Moderate) 10
  • Consider serological proteomic screening with recombinant egg antigens for diagnosing low-intensity S. mansoni infections, particularly useful in areas with reduced parasite loads (Evidence: Moderate) 8
  • Monitor systemic chemokine levels in S. mansoni-infected individuals for biomarker potential, especially in endemic regions like Sudan, comparing infected vs. uninfected cohorts (Evidence: Weak) 9
  • Explore alternative therapeutic options such as miltefosine for S. mansoni infections, particularly in cases where praziquantel resistance or suboptimal efficacy is suspected (Evidence: Expert) 11
  • Utilize serum biomarkers like Carbonic Anhydrase 1 for diagnostic purposes, aiming for thresholds that correlate strongly with active infection status (Evidence: Weak) 14

    • References

    Showing 100 priority papers (full text preferred, most recent first) of 149 indexed.

    1 Alajmi FE. Cross-reactivity and localization of Schistosoma mansoni antigen for immunodiagnosis. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 2026. link 2 Gava SG, de Carvalho IR, Sato MO, Sato M, Fava NMN, Parreiras PM et al.. Advancing schistosomiasis surveillance: standardization and application of an environmental DNA (eDNA)-based approach for detecting Schistosoma mansoni in Brazil. BMC infectious diseases 2025. link 3 Kamel B, Laidemitt MR, Lu L, Babbitt C, Weinbaum OL, Mkoji GM et al.. Detecting and identifying Schistosoma infections in snails and aquatic habitats: A systematic review. PLoS neglected tropical diseases 2021. link 4 Fuss A, Mazigo HD, Mueller A. Detection of Schistosoma mansoni DNA using polymerase chain reaction from serum and dried blood spot card samples of an adult population in North-western Tanzania. Infectious diseases of poverty 2021. link 5 Bezerra DF, Pinheiro MCC, Barbosa L, Viana AG, Fujiwara RT, Bezerra FSM. Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil. Parasitology 2021. link 6 García-Bernalt Diego J, Fernández-Soto P, Crego-Vicente B, Alonso-Castrillejo S, Febrer-Sendra B, Gómez-Sánchez A et al.. Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: towards a ready-to-use test. Scientific reports 2019. link 7 Silva-Moraes V, Shollenberger LM, Siqueira LMV, Castro-Borges W, Harn DA, Grenfell RFQE et al.. Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas?. Memorias do Instituto Oswaldo Cruz 2019. link 8 Silva-Moraes V, Shollenberger LM, Castro-Borges W, Rabello ALT, Harn DA, Medeiros LCS et al.. Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil. PLoS neglected tropical diseases 2019. link 9 Arndts K, Elfaki TEM, Jelden N, Ritter M, Wiszniewsky A, Katawa G et al.. Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts. Clinical and experimental immunology 2019. link 10 Senra C, Gomes LI, Siqueira LMV, Coelho PMZ, Rabello A, Oliveira E. Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA. BMC research notes 2018. link 11 El-Faham MH, Eissa MM, Igetei JE, Amer EI, Liddell S, El-Azzouni MZ et al.. Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. PLoS neglected tropical diseases 2017. link 12 Vonghachack Y, Sayasone S, Khieu V, Bergquist R, van Dam GJ, Hoekstra PT et al.. Comparison of novel and standard diagnostic tools for the detection of Schistosoma mekongi infection in Lao People's Democratic Republic and Cambodia. Infectious diseases of poverty 2017. link 13 Beltrame A, Guerriero M, Angheben A, Gobbi F, Requena-Mendez A, Zammarchi L et al.. Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis. PLoS neglected tropical diseases 2017. link 14 Kardoush MI, Ward BJ, Ndao M. Serum Carbonic Anhydrase 1 is a Biomarker for Diagnosis of Human Schistosoma mansoni Infection. The American journal of tropical medicine and hygiene 2017. link 15 Zhang Y, Jiang Y, Wang Y, Liu H, Shen Y, Yuan Z et al.. Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. International journal of biological sciences 2015. link 16 Siqueira LM, Gomes LI, Oliveira E, Oliveira ER, Oliveira ÁA, Enk MJ et al.. Evaluation of parasitological and molecular techniques for the diagnosis and assessment of cure of schistosomiasis mansoni in a low transmission area. Memorias do Instituto Oswaldo Cruz 2015. link 17 Espírito-Santo MC, Alvarado-Mora MV, Dias-Neto E, Botelho-Lima LS, Moreira JP, Amorim M et al.. Evaluation of real-time PCR assay to detect Schistosoma mansoni infections in a low endemic setting. BMC infectious diseases 2014. link 18 Mduluza T, Mutapi F, Ruwona T, Kaluka D, Midzi N, Ndhlovu PD. Similar cellular responses after treatment with either praziquantel or oxamniquine in Schistosoma mansoni infection. Malawi medical journal : the journal of Medical Association of Malawi 2009. link 19 Wilson RA, Langermans JA, van Dam GJ, Vervenne RA, Hall SL, Borges WC et al.. Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?. PLoS neglected tropical diseases 2008. link 20 Ndegwa D, Krautz-Peterson G, Skelly PJ. Protocols for gene silencing in schistosomes. Experimental parasitology 2007. link 21 Turner P, Lalloo K, Bligh J, Armstrong M, Whitty CJ, Doenhoff MJ et al.. Serological speciation of human schistosome infections by ELISA with a panel of three antigens. Journal of clinical pathology 2004. link 22 Chitsulo L, Engels D, Montresor A, Savioli L. The global status of schistosomiasis and its control. Acta tropica 2000. link00122-4) 23 Lima MS, Gazzinelli G, Nascimento E, Parra JC, Montesano MA, Colley DG. Immune responses during human Schistosomiasis mansoni. Evidence for antiidiotypic T lymphocyte responsiveness. The Journal of clinical investigation 1986. link 24 Boctor FN, Shaheen HI. Immunoaffinity fractionation of Schistosoma mansoni worm antigens using human antibodies and its application for serodiagnosis. Immunology 1986. link 25 Vadas MA, David JR, Butterworth AE, Houba V, Sturrock RF, David L et al.. Functional studies on purified eosinophils and neutrophils from patients with Schistosoma mansoni infections. Clinical and experimental immunology 1980. link 26 Kelsoe GH, Weller TH. Immunodiagnosis of infection with Schistosoma mansoni: enzyme-linked immunosorbent assay for detection of antibody to circulating antigen. Proceedings of the National Academy of Sciences of the United States of America 1978. link 27 Araujo FG, Coelho PM, Pereira LH, Pellegrino J. Schistosoma mansoni: impairment of the cell-mediated immune response in mice. Clinical and experimental immunology 1977. link 28 Pires EHM, Costa NARDS, Barbosa Júnior WL, Gomes ECS. Application of the Sm1-7-qPCR system for identifying S. mansoni DNA in experimentally infected mice. Acta tropica 2025. link 29 Ruas ACL, Brito RMM, Grossi de Oliveira AL, Pinto JC, Cirilo TM, Viana AG et al.. Immunoinformatic predictions and characterization of Schistosoma mansoni peptides as candidates for immunodiagnostic. Diagnostic microbiology and infectious disease 2025. link 30 Ramos LMS, Pereira DSCA, Oliveira LOV, Graeff-Teixeira C. Accuracy of commercial ELISA and ICT for screening schistosomiasis infections at a low endemicity area in Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene 2024. link 31 Allam AF, Kamel MA, Farag HF, Raheem HG, Shehab AY, Hagras NA. Performance of loop-mediated isothermal amplification (LAMP) for detection of Schistosoma mansoni infection compared with Kato-Katz and real-time PCR. Journal of helminthology 2022. link 32 Tanaka M, Kildemoes AO, Chadeka EA, Cheruiyot BN, Sassa M, Moriyasu T et al.. Potential of antibody test using Schistosoma mansoni recombinant serpin and RP26 to detect light-intensity infections in endemic areas. Parasitology international 2021. link 33 Graeff-Teixeira C, Favero V, de Souza RP, Pascoal VF, Bittencourt HR, Fukushige M et al.. Use of Schistosoma mansoni soluble egg antigen (SEA) for antibody detection and diagnosis of schistosomiasis: The need for improved accuracy evaluations of diagnostic tools. Acta tropica 2021. link 34 Fernandes LGV, Fernandes RS, Nascimento ALTO, Leite LCC. A Modified ELISA Method to Evaluate the Interaction of Schistosoma mansoni Proteins with Plasminogen. Methods in molecular biology (Clifton, N.J.) 2020. link 35 Ferrer E, Villegas B, Mughini-Gras L, Hernández D, Jiménez V, Catalano E et al.. Diagnostic performance of parasitological, immunological and molecular tests for the diagnosis of Schistosoma mansoni infection in a community of low transmission in Venezuela. Acta tropica 2020. link 36 Comelli A, Riccardi N, Canetti D, Spinicci M, Cenderello G, Magro P et al.. Delay in schistosomiasis diagnosis and treatment: a multicenter cohort study in Italy. Journal of travel medicine 2020. link 37 Viana AG, Gazzinelli-Guimarães PH, Castro VN, Santos YLOD, Ruas ACL, Bezerra FSM et al.. Discrepancy between batches and impact on the sensitivity of point-of-care circulating cathodic antigen tests for Schistosoma mansoni infection. Acta tropica 2019. link 38 Bezerra FSM, Leal JKF, Sousa MS, Pinheiro MCC, Ramos AN, Silva-Moraes V et al.. Evaluating a point-of-care circulating cathodic antigen test (POC-CCA) to detect Schistosoma mansoni infections in a low endemic area in north-eastern Brazil. Acta tropica 2018. link 39 Ogongo P, Kariuki TM, Wilson RA. Diagnosis of schistosomiasis mansoni: an evaluation of existing methods and research towards single worm pair detection. Parasitology 2018. link 40 Candido RRF, Pierre TGS, Jones MK, Graeff-Teixeira C. Evaluation of the immunogenicity of Schistosoma mansoni egg surface. Revista da Sociedade Brasileira de Medicina Tropical 2017. link 41 Beltrame A, Buonfrate D, Gobbi F, Angheben A, Marchese V, Monteiro GB et al.. The hidden epidemic of schistosomiasis in recent African immigrants and asylum seekers to Italy. European journal of epidemiology 2017. link 42 Espirito-Santo MC, Sanchez MC, Sanchez AR, Alvarado-Mora MV, Castilho VL, Gonçalves EM et al.. Evaluation of the sensitivity of IgG and IgM ELISA in detecting Schistosoma mansoni infections in a low endemicity setting. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2014. link 43 Sarhan RM, Aminou HA, Saad GA, Ahmed OA. Comparative analysis of the diagnostic performance of adult, cercarial and egg antigens assessed by ELISA, in the diagnosis of chronic human Schistosoma mansoni infection. Parasitology research 2014. link 44 Othman RA. Indirect haemagglutination test and ELISA as compared to Kato thick-smear in diagnosing Schistosoma mansoni. Journal of the Egyptian Society of Parasitology 2013. link 45 Hussein HM, El-Tonsy MM, Tawfik RA, Ahmed SA. Experimental study for early diagnosis of prepatent schistosomiasis mansoni by detection of free circulating DNA in serum. Parasitology research 2012. link 46 Carvalho GB, Silva-Pereira RA, Pacífico LG, Fonseca CT. Identification of Schistosoma mansoni candidate antigens for diagnosis of schistosomiasis. Memorias do Instituto Oswaldo Cruz 2011. link 47 Clerinx J, Bottieau E, Wichmann D, Tannich E, Van Esbroeck M. Acute schistosomiasis in a cluster of travelers from Rwanda: diagnostic contribution of schistosome DNA detection in serum compared to parasitology and serology. Journal of travel medicine 2011. link 48 Gentile R, Gonçalves MM, da Costa Neto SF, da Costa MM, Peralta RH, Peralta JM. Evaluation of immunological, parasitological and molecular methods for the diagnosis of Schistosoma mansoni infection before and after chemotherapy treatment with praziquantel in experimentally infected Nectomys squamipes. Veterinary parasitology 2011. link 49 El Aswad Bel D, Doenhoff MJ, El Hadidi AS, Schwaeble WJ, Lynch NJ. Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the serodiagnosis of Schistosoma mansoni. Immunobiology 2011. link 50 Bligh J, Schramm G, Chiodini PL, Doenhoff MJ. Serological analysis of the outcome of treatment of Schistosoma mansoni infections with praziquantel. Annals of tropical medicine and parasitology 2010. link 51 Tararam CA, Farias LP, Wilson RA, Leite LC. Schistosoma mansoni Annexin 2: molecular characterization and immunolocalization. Experimental parasitology 2010. link 52 Helleberg M, Thybo S. High rate of failure in treatment of imported schistosomiasis. Journal of travel medicine 2010. link 53 Nicolls DJ, Weld LH, Schwartz E, Reed C, von Sonnenburg F, Freedman DO et al.. Characteristics of schistosomiasis in travelers reported to the GeoSentinel Surveillance Network 1997-2008. The American journal of tropical medicine and hygiene 2008. link 54 Morais CN, Souza JR, Melo WG, Aroucha ML, Miranda P, Domingues AL et al.. Cytokine profile associated with chronic and acute human schistosomiasis mansoni. Memorias do Instituto Oswaldo Cruz 2008. link 55 Reis EA, Athanazio DA, Cavada BS, Teixeira EH, de Paulo Teixeira Pinto V, Carmo TM et al.. Potential immunomodulatory effects of plant lectins in Schistosoma mansoni infection. Acta tropica 2008. link 56 Helmy MM. Touchdown PCR, ELISA and stool examination for early diagnosing of Schistosoma mansoni in mice. Journal of the Egyptian Society of Parasitology 2007. link 57 Igreja RP, Matos JA, Gonçalves MM, Barreto MM, Peralta JM. Schistosoma mansoni-related morbidity in a low-prevalence area of Brazil: a comparison between egg excretors and seropositive non-excretors. Annals of tropical medicine and parasitology 2007. link 58 Carlo JM, Osman A, Niles EG, Wu W, Fantappie MR, Oliveira FM et al.. Identification and characterization of an R-Smad ortholog (SmSmad1B) from Schistosoma mansoni. The FEBS journal 2007. link 59 Oliveira EJ, Kanamura HY, Takei K, Hirata RD, Nguyen NY, Hirata MH. Application of synthetic peptides in development of a serologic method for laboratory diagnosis of schistosomiasis mansoni. Memorias do Instituto Oswaldo Cruz 2006. link 60 Gonçalves MM, Barreto MG, Peralta RH, Gargioni C, Gonçalves T, Igreja RP et al.. Immunoassays as an auxiliary tool for the serodiagnosis of Schistosoma mansoni infection in individuals with low intensity of egg elimination. Acta tropica 2006. link 61 Suzuki T, Osada Y, Kumagai T, Hamada A, Okuzawa E, Kanazawa T. Early detection of Schistosoma mansoni infection by touchdown PCR in a mouse model. Parasitology international 2006. link 62 Ganley-Leal LM, Guarner J, Todd CW, Da'Dara AA, Freeman GL, Boyer AE et al.. Comparison of Schistosoma mansoni irradiated cercariae and Sm23 DNA vaccines. Parasite immunology 2005. link 63 Bethony J, Williams JT, Brooker S, Gazzinelli A, Gazzinelli MF, LoVerde PT et al.. Exposure to Schistosoma mansoni infection in a rural area in Brazil. Part III: household aggregation of water-contact behaviour. Tropical medicine & international health : TM & IH 2004. link 64 Doenhoff MJ, Wheeler JG, Tricker K, Hamilton JV, Sturrock RF, Butterworth AE et al.. The detection of antibodies against Schistosoma mansoni soluble egg antigens (SEA) and CEF6 in ELISA, before and after chemotherapy. Annals of tropical medicine and parasitology 2003. link 65 Burlandy-Soares LC, de Souza Dias LC, Kanamura HY, de Oliveira EJ, Ciaravolo RM. Schistosomiasis mansoni: follow-up of control program based on parasitologic and serologic methods in a Brazilian community of low endemicity. Memorias do Instituto Oswaldo Cruz 2003. link 66 Idris MA, Shaban M, Richter J, Moné H, Mouahid G, Ruppel A. Emergence of infections with Schistosoma mansoni in the Dhofar Governorate, Oman. Acta tropica 2003. link00197-9) 67 Kamel MI, Moustafa YA, Foda N, Khashab S, Moemen M, Abo el-Naga RM. Impact of schistosomiasis on quality of life and productivity of workers. Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit 2002. link 68 Degu G, Mengistu G, Jones J. Some factors affecting prevalence of and immune responses to Schistosoma mansoni in schoolchildren in Gorgora, northwest Ethiopia. Ethiopian medical journal 2002. link 69 Mostafa NE, Awad A, Shalaby M. Low avidity IgG antibodies in diagnosis of recent human schistosomiasis. Journal of the Egyptian Society of Parasitology 2002. link 70 Sayed HA, El Ayyat AA, Sabry HY, Amer NM. Upgrading of Kato-Katz technique for diagnosis of S. mansoni infection in rural Egypt. Journal of the Egyptian Society of Parasitology 2002. link 71 Viana Lde G, Rabello A, Katz N. Antibody subclass profile and avidity during acute and chronic human Schistosoma mansoni infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 2001. link90038-0) 72 Polman K, Diakhate MM, Engels D, Nahimana S, Van Dam GJ, Falcão Ferreira ST et al.. Specificity of circulating antigen detection for schistosomiasis mansoni in Senegal and Burundi. Tropical medicine & international health : TM & IH 2000. link 73 Santos MM, Garcia TC, Orsini M, Disch J, Katz N, Rabello A. Oral fluids for the immunodiagnosis of Schistosoma mansoni infection. 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    Original source

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      Cross-reactivity and localization of Schistosoma mansoni antigen for immunodiagnosis. — Alajmi FE Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (2026)
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      Advancing schistosomiasis surveillance: standardization and application of an environmental DNA (eDNA)-based approach for detecting Schistosoma mansoni in Brazil. — Gava SG, de Carvalho IR, Sato MO, Sato M, Fava NMN, Parreiras PM et al. BMC infectious diseases (2025)
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      Detecting and identifying Schistosoma infections in snails and aquatic habitats: A systematic review. — Kamel B, Laidemitt MR, Lu L, Babbitt C, Weinbaum OL, Mkoji GM et al. PLoS neglected tropical diseases (2021)
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      Detection of Schistosoma mansoni DNA using polymerase chain reaction from serum and dried blood spot card samples of an adult population in North-western Tanzania. — Fuss A, Mazigo HD, Mueller A Infectious diseases of poverty (2021)
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      Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil. — Bezerra DF, Pinheiro MCC, Barbosa L, Viana AG, Fujiwara RT, Bezerra FSM Parasitology (2021)
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      Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: towards a ready-to-use test. — García-Bernalt Diego J, Fernández-Soto P, Crego-Vicente B, Alonso-Castrillejo S, Febrer-Sendra B, Gómez-Sánchez A et al. Scientific reports (2019)
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      Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil. — Silva-Moraes V, Shollenberger LM, Castro-Borges W, Rabello ALT, Harn DA, Medeiros LCS et al. PLoS neglected tropical diseases (2019)
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      Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts. — Arndts K, Elfaki TEM, Jelden N, Ritter M, Wiszniewsky A, Katawa G et al. Clinical and experimental immunology (2019)
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      Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. — Zhang Y, Jiang Y, Wang Y, Liu H, Shen Y, Yuan Z et al. International journal of biological sciences (2015)
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