Schistosoma haematobium

In brief

What it is, and how it gets in

Schistosomiasis is caused by blood flukes of the genus Schistosoma, flatworms that live inside human blood vessels. It is caught not by swallowing anything but by skin contact with fresh water: larvae released by particular freshwater snails penetrate unbroken skin, and the infection that follows is chronic, persisting for years unless treated ¹. The first weeks can bring a self-limiting allergic illness known as Katayama fever; after that the disease settles into one of two patterns depending on species. The intestinal pattern brings abdominal pain and bloody diarrhea and can end in scarring of the liver and dangerously high pressure in the vein that carries blood from the gut to it, called portal hypertension. The urogenital pattern, which is this species, brings painful urination and blood in the urine, and its recognized complications are kidney failure and squamous-cell carcinoma of the bladder ¹.

The life cycle cannot be completed without the snail, which is why snail control is a lever on transmission. S. haematobium uses Bulinus truncatus and its relatives, S. mansoni uses Biomphalaria glabrata, and S. japonicum uses Oncomelania hupensis ³. The loop closes through water. Eggs that leave in urine hatch in fresh water into a miracidium, a swimming larva that must find a Bulinus snail, and what happens inside the snail decides transmission: a 2026 review of snail immunity describes outcomes running from full resistance to high compatibility, with the divergence set in the first 12 to 48 hours after penetration, according to whether the invading miracidia are eliminated or go on to develop sporocysts ²⁵. In a compatible snail they do, and the snail then sheds the cercaria, a second and different larval stage, and the one that penetrates human skin ^1,25. One egg can therefore become many infective larvae, which is why breaking the snail step breaks the cycle. Snail control also has more to work with than it did: by 2024 genome assemblies were public for all three vector genera, including the first for African vectors, Bulinus truncatus among them, which is what a search for molecular targets in the snail requires ²⁶. Adult worms colonize human blood vessels for years, evading the immune system while a single pair sheds hundreds to thousands of eggs a day; in this species the pair settles in the vesical venous plexus, the mesh of small veins wrapped around the bladder, so the eggs are laid where they can cross the bladder wall and leave in urine ^1,4. The worm survives that long partly because of its tegument, a single fused layer of cytoplasm covering its whole surface that can carry host molecules on its outer face ¹⁸.

The eggs are the point. Colley and colleagues put it plainly: eggs must either leave the body in excreta or become trapped in nearby tissues, and trapped eggs induce a distinct immune-mediated granulomatous response — a tight ball of immune cells around something the body can neither kill nor expel. That response, not the worm, produces anemia, stunted growth, impaired thinking, reduced fitness, and the organ damage that includes urogenital inflammation and scarring ⁴. Every mechanism later proposed for cancer starts from a trapped egg.

The genomes arrived late and were candid about how little was known. The S. mansoni genome, published in 2009, is 363 megabases and at least 11,809 genes, with deficits in fat metabolism that make the worm dependent on its host and more than 300 proteases ⁶. A high-quality genome for S. haematobium itself followed in 2019, whose authors called it "this carcinogenic worm" and wrote that at the molecular level little was known about the fluke or the disease it causes ²⁷. That sentence, from the specialists, is the honest baseline for everything in the mechanism section below.

The whole history, including the parts that were overturned

The arc runs from a worm found at autopsy in Cairo to a cancer classification, and then to the quiet inversion of the pathology that classification was built on. Theodor Bilharz, who lived from 1825 to 1862, is credited with discovering the parasite ³⁹; the finding is conventionally dated 1851 and the published description the year after, which is why the formal species authority carried in current papers is Schistosoma haematobium (Bilharz, 1852) Weinland, 1858 — the two dates are the finding and the naming, not a disagreement ². The cancer suspicion came half a century later, with Goebel in 1905, and was made concrete in 1911 by A. R. Ferguson, professor of pathology in Cairo, who reported a likely association between bladder carcinoma and egg granulomas in a series of 40 autopsies ⁴⁰.

For most of the twentieth century the case rested on circumstance: bladder cancer was common where the parasite was common, the patients were young men rather than older people of both sexes, and squamous carcinoma predominated in endemic areas while urothelial carcinoma predominated where the parasite was absent ⁴⁰. A French review summarizing the field states the limitation squarely: evidence of a positive correlation came only many decades later, from case-control studies adjusted for age, sex, type of dwelling and tobacco ⁴⁰. The classification of 1994 sits on top of that long circumstantial period and a short run of adjusted studies.

Then the ground moved. Egyptian control of the parasite improved from about 1970 onward ⁴⁰, and three independent Egyptian series covering 1970 to 2010 found that the cancer had changed type: squamous carcinoma collapsed and urothelial carcinoma took its place ^13,20,21. By 2019 Egyptian pathologists were arguing in print that the old concept should be re-evaluated and that the histological method used to confirm the infection in tumors was not accurate ⁴¹. In 2020 a Danish study with no schistosomiasis in it found chronic urinary infection associated with bladder squamous carcinoma far more strongly than the parasite ever was in Egypt ⁴². Both findings point the same way: toward sustained inflammation rather than this organism in particular. One caution about geography belongs here. The inversion is an Egyptian observation, and it is not yet the picture everywhere transmission persists: a review of 481 histologically confirmed bladder cancers diagnosed over ten years at a referral pathology department in Tanzania’s Lake Victoria zone found squamous carcinoma still the commonest type at 57.0%, against 37.6% transitional-cell and 5.4% adenocarcinoma, with S. haematobium eggs seen in 25.2% of specimens and significantly associated with the squamous type (p = 0.001), at a mean age of 55 ¹². Read together, the two bodies of work say the histology follows the infection rather than the calendar.

The drug has its own history of not being understood. Praziquantel was in clinical use for roughly four decades, given to hundreds of millions of people, before its molecular target was identified in 2021 as a calcium-permeable TRPM channel (transient receptor potential melastatin, a family of pores through the cell membrane) in the worm, engaged at a hydrophobic pocket, which floods the parasite with calcium and paralyzes it ⁴³. In 2022 WHO rewrote the public health strategy around it ⁷, and in 2023 a child-friendly form reached a published phase 3 result ¹⁷.

What it does to a body

The clinical picture of urogenital schistosomiasis is dysuria — pain on passing urine — and hematuria, blood in the urine, with renal failure and bladder squamous carcinoma as the recognized complications of long infection ¹. The damage is cumulative and mostly silent in between: eggs pushed into the bladder wall are walled off in granulomas, the wall thickens and scars, and the lining changes character. In a cross-sectional study of 54 patients at an Egyptian university hospital, squamous metaplasia was present in 38 (70.4%) — non-keratinizing in 20 and keratinizing in 18 — and invasive squamous carcinoma in 11 (20.4%) ²³. That is a referral series with no comparison group, so it describes what the pathology looks like, not how common it is in the population.

A 2024 systematic review of 94 studies drew the biology together: a mixed immune response dominated by the type 2 pattern, more regulatory T and B cells, molecular changes that weaken the epithelial barrier including raised metalloproteinase expression, more of the proteins p53 and BCL2 — p53 is the tumor-suppressor protein that normally stops a damaged cell dividing, so more of it marks cells under stress rather than better protection, and the same gene, written TP53, is found mutated in a third of bilharzial bladder tumors ³⁷; BCL2 is a protein that blocks the cell’s self-destruct program — and disturbance of the bacterial communities of the urinary, intestinal and genital tracts. Its authors conclude that the parasite promotes cellular transformation with oncogenic potential — a careful phrase that claims a direction, not a completed cancer ⁵.

In women the eggs also lodge in the genital tract, producing female genital schistosomiasis, which is both a disease in itself and a link to another infection. In a rural Zimbabwean community, 527 sexually active women aged 20 to 49 were examined; among the permanent residents — those with more than three years’ residency — the human immunodeficiency virus (HIV) was present in 41% (29/70) of those with laboratory-proven genital schistosomiasis against 26% (96/375) of egg-negative women, an odds ratio of 2.1 (95% CI 1.2–3.5, P = 0.008) and 2.9 (95% CI 1.11–7.5, P = 0.030) after adjustment. Community-wide HIV prevalence was 29%. All seven women who became HIV positive during the study had signs of the parasite at baseline ²⁴. That is a cross-sectional study with a small incident group, so it establishes an association that the authors themselves said needed prospective confirmation.

A recognized carcinogen sitting in genital tissue raises a second cancer question, and the answer is not yet in. Whether this parasite also acts on the cervix, directly or through the human papillomavirus, has been asked properly and cannot yet be answered. A systematic review searching five databases to April 2024 found only six eligible studies and 1,081 women, all in sub-Saharan Africa: one Zimbabwean study reported more high-risk human papillomavirus — the virus that causes cervical cancer — in women with genital schistosomiasis at baseline (adjusted odds ratio 1.9, 95% CI 1.1–3.6) but no association after five years of follow-up; a KwaZulu-Natal study found more human papillomavirus of any type (adjusted odds ratio 1.71, 95% CI 1.14–2.56); and a Madagascan study found none (odds ratio 1.0, 95% CI 0.82–1.2). Of four studies of pre-cancer, one found more abnormalities on visual inspection with acetic acid in women with molecular disease (adjusted odds ratio 6.08, 95% CI 1.58–23.37) and three found no association. The reviewers concluded that the data were too few and too weak either to confirm or to exclude a link ⁴⁶. A 2025 pilot went to the tissue instead. Cervical brush samples from 39 Tanzanian women — 20 infected, 19 not — were sequenced before and four to twelve months after praziquantel: nine genes were expressed differently in infection, 29 differed between women whose infection had been cleared and women who had never been infected, and most of the differentially expressed genes in both groups were genes reported as raised in cancers ⁴⁷. Thirty-nine women is a pilot and its authors say so, but it is the first molecular evidence here, and it points the uncomfortable way.

The genital form remains badly served. Morbidity comes from inflammation around trapped eggs in the genital tract of women and men; awareness is largely absent among affected communities and health workers; there are no agreed screening or diagnostic methods, no reliable burden estimates, and no WHO guidelines to inform practice — the conclusions of a 2022 research-network meeting in Lusaka attended by more than 150 researchers and stakeholders ⁴⁸. In one Nigerian pilot, 23.4% of the 47 women examined were passing eggs in urine — an “egg-patent” infection, meaning one heavy enough to be found down a microscope — while 38.3% had yellow sandy patches on colposcopy, and every cervical smear showed atypia ⁴⁹.

Three years on from that meeting there is a framework, if still no guideline. A 2026 Lancet Microbe series proposes splitting the condition by how it was found — visual, histological and molecular female genital schistosomiasis — because those three definitions do not pick out the same women ⁵⁰, and its companion paper places it among the other infections of the same tissue, the human immunodeficiency virus and human papillomavirus by sexual transmission, bacterial vaginosis and thrush by other routes, and flags the zoonotic and hybrid schistosomes now turning up in it ⁵¹. Field numbers have arrived too. In two endemic areas of southern Malawi, 950 women were examined by hand-held colposcopy with cervicovaginal swabs: 26.9% had the visual disease and 8.2% had parasite DNA in the genital tract, while only 6.5% were passing eggs in urine — and some villages had high molecular prevalence although fewer than 10% of their schoolchildren had urinary infection, which is the threshold that decides whether a village is treated at all ⁵². The burden now commonly quoted is 40 to 56 million women and girls, a number still built from modeling rather than measurement ⁵³.

The proposed mechanisms, and what class of evidence each rests on

Nine mechanisms are in circulation, and they are not equally supported. The honest summary is that the human evidence is almost entirely associational, the causal experiments are in rodents and cell culture, and a 2020 paper from the leading bladder-schistosomiasis laboratory still described the mechanisms as largely unknown, partly because of a historical lack of animal models ²⁸. A 2017 review reached the same conclusion from the clinical side: the mechanisms are poorly understood for want of a convenient animal model ⁴⁰. A 2026 review of infection-driven bladder cancer says the same of the present: mechanistic insight remains limited for most of the pathogens implicated, this one included ⁵⁴.

The strongest experimental result is also the most awkward for the simple story. When mouse bladders were injected with S. haematobium eggs with or without a chemical nitrosamine, squamous metaplasia appeared in the eggs-plus-nitrosamine group at week 12 and in no other group, and the proliferation marker Ki-67 rose where eggs were combined with a bladder carcinogen ⁵⁵. Read strictly, eggs alone did not produce the change in that experiment. If that holds, the parasite is a co-factor rather than a sufficient cause — which fits the Egyptian observation, made in 1987, that heavily infected and egg-negative tumors looked the same ³⁰.

The host's own immune wiring carries a large share of the mechanism. Mice lacking the interleukin-4 receptor mounted significantly weaker granulomatous responses to injected eggs, and the urothelial proliferation, extra chromosome copies and cell-cycle skewing seen in normal mice did not occur in them; exposing bladder lining cells to interleukin-4 directly shifted their cell cycle and increased phosphorylation of AKT, a growth signal ²⁸. The egg protein IPSE — short for the interleukin-4-inducing principle of schistosome eggs — which only the egg stage makes, enters human bladder cells in culture and is carried into the nucleus by its own address sequence ³⁴; but given to mice before a bacterial bladder infection it reduced rather than increased the resulting damage, so its role in the bacterial co-infection story is unresolved ³⁵.

The chemical arms are older and thinner. Nitrosamines were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer, and nitrosating bacteria were more common in infected people, especially at higher infection intensity ²⁹. Beta-glucuronidase, which reactivates detoxified carcinogens, rose in infected hamsters ³¹, and the enzyme and a bacterial nitrate reductase were the mechanism an Egyptian pathologist proposed in 1987 ³⁰ — both bacterial products, which makes the parasite the thing that lets the chemistry happen rather than the source of it. The parasite-derived catechol estrogens are the one proposed carcinogen the worm might make itself, measured in human urine, with catechol estrogen quinones and quinone-DNA adducts identified in the cases and metabolites derived directly from 8-oxo-dG — 8-oxo-7,8-dihydro-2'-deoxyguanosine, the standard chemical marker of oxidative DNA damage — found in all 40 Angolan urines in one series ^32,33.

How strong the cancer link actually is

Two things are true at once, and the page exists to hold both. The International Agency for Research on Cancer places S. haematobium in Group 1 — the category for agents where the evidence of causing cancer in humans is judged sufficient — and has done since 1994 ^9,11. In endemic regions squamous carcinoma accounted for 53–69% of bladder carcinoma cases, a pattern not seen where the parasite is absent ¹¹. And the parasite is still on IARC's current list of 12 Group 1 infectious agents ¹⁰.

But the best-adjusted measurement of individual risk is modest. In Alexandria between 1994 and 1996, 190 people with newly diagnosed, histologically confirmed invasive bladder cancer were compared with 187 hospital controls. Forty-five percent of cases and 37% of controls reported a history of urinary schistosomiasis, and after adjustment for age, sex, education, smoking, other urinary infections and high-risk occupations the odds ratio was 1.72, with a 95% confidence interval of 1.0 to 2.9 — a lower bound sitting exactly on no effect. The authors' own words were "significantly, but modestly, associated", explaining some 16% of bladder cancers in that population ¹⁴. In the companion paper, on the same population, cigarette smoking gave an odds ratio of 6.6 (95% CI 3.1–13.9) and explained about 75% of male cases ¹⁵.

The same Alexandria data carry the best available signal about timing. Risk was higher in people whose infection was first diagnosed before age 15 (odds ratio 3.3) and in those diagnosed 35 or more years earlier (3.0), and the two exposures together were much worse than either alone: male ever-smokers with a schistosomiasis history had an odds ratio of 15.8 against never-smokers without one ¹⁴. No study reports a measured latency interval, so decades-long latency is an inference from this pattern rather than a measurement.

Then there is the control experiment nobody designed. In Denmark, where the parasite does not occur, 12,271 histologically verified bladder cancers from 2000 to 2015 were compared with matched cancer-free controls, using prescriptions for urinary-infection antibiotics as a proxy for chronic infection. The 333 squamous carcinomas — 2.7% of all bladder cancers — were associated with heavy antibiotic use at an odds ratio of 11.4 (95% CI 7.6–17.2) with a clear dose-response (P < 0.001), while urothelial carcinoma was not associated at all (1.13, 95% CI 0.97–1.32). An antibiotic not used for urinary infection showed no association ⁴². The study lacked smoking data, which its authors addressed with a bias analysis. Read beside the Egyptian odds ratio of 1.72, it suggests that what selects the squamous phenotype is sustained lower urinary tract inflammation, and that this parasite is an unusually durable way of producing it rather than a uniquely genotoxic organism.

How it is found, and how it is missed

Conventional diagnosis is finding eggs down a microscope, in urine for this species and stool for the intestinal ones, and the Lancet review notes in the same breath that sensitivity might be low ¹. How low has now been measured carefully. In Pemba, Tanzania, in 2025, with five days of urine filtration microscopy as the reference, a single sample found 61.2% of infections (95% CI 55.3–67.1). The best single-sample test was a microscopy-based artificial-intelligence scanner at 76.7% — a figure to read alongside the study’s own disclosure that two of its authors are employed by the company that makes the scanner — with quantitative PCR, the polymerase chain reaction, which copies a target stretch of DNA until it can be counted, at 76.0%, recombinase polymerase amplification at 56.1%, a dipstick for blood at 44.6%, and a circulating-antigen assay at 30.6%. Specificity was above 92% for everything except qPCR and recombinase amplification ⁵⁶.

That matters for more than clinical care. Cure rates, prevalence thresholds and the historical estimates of how many bladder cancers were schistosomal all rest on egg detection, and an insensitive test flatters every one of them. Cochrane's review of 90 studies found that the dipstick for microscopic blood in urine was the best of the simple tests against microscopy, at 75% sensitivity (95% CI 71–79) and 87% specificity (95% CI 84–90) across 102,447 participants, and that the point-of-care circulating cathodic antigen test performed badly for this species, with a pooled sensitivity of 39% and a confidence interval from 6% to 73% ⁵⁷.

Molecular and antigen methods do better in principle and vary enormously in practice. A real-time PCR for the species-specific Dra1 repeat detected infection in 22 of 23 serum samples from confirmed cases and could find the equivalent of half an egg per gram ⁵⁸. A laboratory antigen assay reached 97% sensitivity by latent class analysis — a way of estimating a test’s accuracy when no available test is good enough to serve as the truth, which means the figure depends on the model as well as on the test — in a low-prevalence Zanzibari setting, and found roughly three times as many infections as microscopy ⁵⁹. A 2026 systematic review of field tests put loop-mediated isothermal amplification and recombinase polymerase amplification highest, at 94.7% and 94.1% sensitivity, with the point-of-care antigen strip at 49.8% ⁶⁰, and a 2026 Gabonese study of parasite DNA in 20 microliters of plasma estimated 74.0% sensitivity, with microscopy still the most specific test at 94.9% ⁶¹.

Tissue is its own problem. Calcified eggs in a bladder biopsy are how a tumor gets called schistosomal, and the pathologists who use that method have said it does not work well: in a 2019 Egyptian series, schistosomiasis was histologically confirmed in only 19 cancer cases, of which exactly one was squamous, and the authors wrote that relying on histopathology to confirm the infection appears to be non-accurate and leads to irrelevant results ⁴¹. Two things make that method leak, and they leak in opposite directions. Eggs lie in patches in the bladder wall, so whether any are seen depends on which blocks of tissue happened to be cut and read — a negative section is not a negative bladder. And a calcified egg is durable: it records that eggs were laid there at some point, not that a living worm was present when the tumor began, so egg positivity in a specimen can no more date the exposure than a mutation can. Since the historical case-mix estimates used that same method, they are uncertain in both directions, and soft at both ends. For the genital form there is no reference test at all: two expert reviewers of the same 527 sets of cervical images agreed only slightly, with a kappa of 0.16 — a scale on which 0 is the agreement expected by chance and 1 is perfect. Reviewer 1 diagnosed disease in 35.3% (165/468) of the images he judged interpretable and Reviewer 2 in 63.6% (265/417) of his, and the two agreed on a diagnosis for only 38.7% (204/527) of the women ⁶². That disagreement is now being treated as an engineering problem rather than a fact of nature: the group behind the image review argues that cervical photographs are a good target for computer vision precisely because the egg-related changes are subtle, patchy and inconsistently graded by trained humans, and sets out why accurately labeling the training images, not the model, is the obstacle ⁶³.

• Urine filtration microscopy with an egg count, and the dipstick that stands in for itA measured volume of urine is passed through a filter and the eggs on it are counted; it is the test WHO programs are built on, and the threshold for a heavy infection is 50 eggs or more per 10 mL ⁶⁷. Where microscopy is impractical, a reagent strip read for microscopic blood is used as a cheap proxy — a test for bleeding, not for the worm ⁵⁷.The program standard, and still the reference test in accuracy studies ⁵⁶Against five days of filtration as the reference, one sample of urine found 61.2% (95% CI 55.3–67.1) of infections in a near-elimination setting in Pemba, Tanzania, in 2025, and a strip found 44.6% ⁵⁶. Pooled against microscopy across 74 studies and 102,447 participants, the strip was 75% sensitive (95% CI 71–79) and 87% specific (95% CI 84–90) ⁵⁷.Light infections, and anything shed on a day you did not sample; sensitivity rises with infection intensity, and multiple days are better but hard to run in the field ⁵⁶. The strip misses infections that do not bleed and flags other causes of blood in urine ⁵⁷.
• Circulating antigen tests (CAA, circulating anodic antigen; CCA, circulating cathodic antigen)These look for a sugar-protein the living worm sheds into blood or urine, so a positive means active infection rather than past exposure ⁵⁹.Surveillance in low-transmission settings, and researchThe laboratory up-converting-particle CAA assay reached 97% sensitivity (95% CI 91–100) by latent class analysis on Pemba, Zanzibar, in samples collected in 2013 and published in 2015 ⁵⁹, but in the 2025 Pemba comparison the same family of assay found only 30.6% of infections ⁵⁶. The simpler point-of-care CCA strip performs poorly for this species: pooled sensitivity 39% (95% CI 6–73) in Cochrane's review ⁵⁷ and 49.8% in a 2026 meta-analysis ⁶⁰.Performance depends heavily on format, sample handling and the reference test used, and the published range is wide enough that a single quoted figure is misleading ^56,57,59,60.
• DNA amplification: PCR (polymerase chain reaction), LAMP (loop-mediated isothermal amplification), RPA (recombinase polymerase amplification)These copy a repeated stretch of parasite DNA — for this species the Dra1 repeat — from urine, stool, serum or plasma until it can be detected ⁵⁸.Travelers and migrants with low egg output, and research surveysA Dra1 real-time PCR detected the parasite in 22 of 23 serum samples from parasitologically confirmed cases, with an analytical limit of 0.5 eggs per gram ⁵⁸. In Pemba in 2025, qPCR on one sample found 76.0% of infections ⁵⁶; in a 2026 systematic review the field methods LAMP and RPA reached sensitivities of 94.7% and 94.1% ⁶⁰; and a 2026 Gabonese study of plasma cell-free DNA estimated 74.0% sensitivity (95% credible interval 57.2–90.8) ⁶¹.Specificity is the weak side — in Pemba every test but qPCR and RPA exceeded 92% specificity, and those two did not ⁵⁶. DNA can also persist after cure, so a positive does not prove a living worm.
• Eggs in a tissue sectionPathologists look for schistosome eggs, often calcified, in bladder biopsies; this is how tumors were historically labeled schistosomal ^23,41.Diagnosis of the cancer, and the basis of every historical estimate of how many bladder cancers were schistosomalIt finds a great deal when infection is heavy: squamous metaplasia in 38 of 54 Egyptian biopsies (70.4%) and invasive squamous carcinoma in 11 of 54 (20.4%) ²³.Egyptian pathologists reported in 2019 that schistosomiasis was histologically confirmed in only 19 of their cancer cases, and concluded that relying on histopathology to confirm the infection "appears to be non-accurate" ⁴¹. It leaks in both directions: eggs lie in patches, so a negative section is not a negative bladder, and a calcified egg is durable, so finding one records that eggs were laid there at some point rather than that a living worm was present when the tumor began. Since the same method produced the historical numbers, those numbers are uncertain in both directions.
• Hand-held colposcopy for female genital schistosomiasisThe cervix and vagina are inspected for sandy patches, rubbery papules and abnormal vessels, the agreed visual signs of eggs in the genital tract ⁶².The current reference standard for female genital schistosomiasis, for want of anything better ^48,62Poor as a standard: two expert physicians read the same 527 Zambian image sets and diagnosed visual disease in 35.3% (165/468 of the images Reviewer 1 judged interpretable) and 63.6% (265/417 for Reviewer 2), agreeing on a diagnosis for only 38.7% (204/527) of the women — a kappa of 0.16, which is "slight" agreement ⁶².There is no diagnostic reference test and no WHO guideline for the condition, so prevalence estimates and treatment decisions rest on a reading that two experts do not reproduce ^48,62.

What is done about it

There is one drug. Praziquantel is first-line treatment, and it is also what is given to whole communities in what public health calls preventive chemotherapy — treating everyone in a place whether or not anyone has been tested, a term that has nothing to do with cancer chemotherapy ¹. Its honest numbers come from a meta-analysis of 55 trials and 19,499 subjects given praziquantel, a comparator or placebo, with cure rate assessed in 17,017 and tolerability in 12,435: at the recommended single dose of 40 mg/kg, the cure rate was 77.1% (95% CI 68.4–85.1) for S. haematobium, 76.7% for S. mansoni, 94.7% for S. japonicum, and 63.5% for mixed infections. Egg reduction averaged 94.1% for this species. More than half of treated people — 56.9% (95% CI 47.4–67.9) — had an adverse event, most often abdominal pain at 31.1%. The authors concede that efficacy may be lower than expected at some sites and that the test of cure is imperfect ¹⁶, which means the true failure rate is plausibly higher than the reported one. The dose itself is no longer settled at the young end. A double-blind, placebo-controlled randomized trial in Uganda gave 354 children aged 12 to 47 months either the recommended single 40 mg/kg or two 40 mg/kg doses three hours apart, and cure at four weeks was 67% on the standard dose against 90% on the double, with no difference in adverse events ⁶⁴. That trial treated S. mansoni, not this species, in preschool children, and it is a phase 2 result, so it does not rewrite the 77.1% figure for S. haematobium. It does show the recommended dose failing a third of the patients hardest to treat.

The drug also has a hard biological limit that is usually stated loosely and can be stated exactly: it does not kill young worms — the stages that have already entered a human body but have not yet matured — and juveniles three to four weeks into an infection shrug off drug concentrations that paralyze adults ⁶⁵. So a dose clears the worms a person has grown, not the ones still maturing, and not the ones acquired next week in the same water. The same paper notes field isolates with heritable reductions in susceptibility and laboratory selection of resistance ⁶⁵ — a real concern for a single-drug strategy, and the reason the 2021 identification of praziquantel's molecular target matters: that target is a TRPM channel, and a single amino acid substitution in its binding pocket is enough to change sensitivity ⁴³. That work was done in part by employees of Merck KGaA, which manufactures praziquantel and runs the largest donation program for it, and the conflict belongs on the record ⁴³.

Until recently the youngest children were left out, because the standard tablet is large, bitter and hard to dose in a toddler ⁶⁶. The Pediatric Praziquantel Consortium developed a dispersible tablet of the active half of the molecule, arpraziquantel, and the 2023 phase 3 trial in Côte d'Ivoire and Kenya prescreened 2,663 children and enrolled 288 aged three months to six years. Its one randomized comparison, in 4-to-6-year-olds infected with S. mansoni, gave a cure rate of 87.8% (95% CI 79.6–93.5) on arpraziquantel 50 mg/kg against 81.3% (95% CI 67.4–91.1) on standard praziquantel 40 mg/kg; the 90 children with S. haematobium were in single-arm cohorts, one of them at 60 mg/kg, so the trial reports no comparative cure rate for this species. Abdominal pain occurred in 14%, diarrhea in 9%, vomiting in 6% and somnolence in 7%, with no safety concerns identified. The trial was funded in part by the healthcare business of Merck KGaA ¹⁷.

Policy changed around the drug in 2022. WHO's new guidelines made six recommendations: widen preventive chemotherapy from mainly school-aged children to everyone from two years upward, lower the prevalence threshold at which annual treatment is given, and treat more often ⁷. The target that programs are measured against is narrower than it sounds — elimination as a public health problem is defined as fewer than 1% of people carrying heavy-intensity infections, meaning 50 or more S. haematobium eggs per 10 mL of urine — and a 2022 viewpoint by authors from the United States Centers for Disease Control and Prevention (CDC), WHO-linked and academic, argues that the evidence for that definition is inadequate and that the morbidity left behind after mass treatment is subtler than the measure can see ⁶⁷. The target those programs are working to is elimination of schistosomiasis as a public health problem worldwide by 2030, and the most current national measurement of progress comes from Ethiopia. A survey of 121,593 children at 4,258 sites between June 2021 and October 2024, after a decade of treatment, found a combined prevalence of 5.4% (95% CI 5.0–5.9) — 5.2% for S. mansoni and 1.0% for S. haematobium — cut the number of people above the threshold for annual treatment from 25.6 million to 10.8 million, and put heavy-intensity infection at 0.2%, already below the 1% the definition uses ⁶⁸. Which is the shape of the problem the viewpoint above describes: the metric is being met while the morbidity it was chosen to stand for goes unmeasured. Nothing in any of this has been shown to reduce bladder cancer incidence, because that study has not been done.

Its cousins, and why they are classified differently

The intestinal species live in the veins draining the gut and damage the liver: abdominal pain and bloody diarrhea, then hepatic fibrosis, portal hypertension, an enlarged spleen and bleeding from swollen veins ¹. Their cancer status is not the same as S. haematobium's, and the difference is instructive. Only S. haematobium is in Group 1; S. mansoni sits in Group 3, which means not classifiable as to carcinogenicity in humans because the evidence is inadequate — explicitly not a finding of safety ¹⁹. One review places S. japonicum in Group 2B, possibly carcinogenic to humans, in connection with liver and colorectal cancer ⁶⁹, and a 2025 review notes that six fluke species in total are within IARC's scope ⁷⁰.

The S. mansoni evidence shows what Group 3 looks like from inside. Mechanistically it is respectable: eggs and egg antigens switched on Wnt/beta-catenin signaling, the proto-oncogene c-Jun, Cyclin D1 and markers of DNA damage in gut lining cells, and the same hallmarks were then confirmed in colon biopsies from infected patients ⁷¹. Clinically it is thin. The largest human dataset, 1,446 patients with liver cancer at a Cairo clinic over a decade, gave an adjusted odds ratio of 1.589 (95% CI 1.187–2.127) for prior infection, in a population where hepatitis C is pervasive and where the infected group differed systematically in sex, smoking, diabetes and liver function ⁷². Below that sits a Brazilian series of seven patients, all with coexisting liver disease or hepatitis B antibodies, whose authors wrote that it remains unclear whether the parasite alone has carcinogenic potential ⁷³.

For S. japonicum the human evidence is older and genuinely cohort-based. The Japanese study of 2,067 residents aged over 30 found excess deaths from liver cirrhosis in both sexes, liver cancer in men only and colon cancer in women only, with the excess rising with years of residence in the area before 1957 for cirrhosis and for colon cancer in women ⁴⁴. A matched case-control study in rural Sichuan found previous infection associated with liver cancer at an odds ratio of 3.7 (95% CI 1.0–13) and colon cancer at 3.3 (95% CI 1.8–6.1), with attributable fractions of 27% and 24% ⁷⁴. Read the intervals: the colon estimate is reasonably precise, the liver estimate runs from no effect to thirteenfold. Separately, schistosomal colorectal cancers behave as a molecularly distinct group — c-MYC amplification predicted worse survival in schistosomal tumors (P < 0.001) and not in the others (P = 0.155) — which is a statement about prognosis, not about cause ⁷⁵.

The genus is also moving. S. haematobium interbreeds with the cattle schistosome S. bovis, human hybrids cluster in the Senegal River Basin, cattle have been shown to carry both the cattle species and hybrids in Benin, and pure S. bovis plus human-infective hybrids have been found in Corsica ^2,22. A species list and a carcinogen classification are both snapshots of something that is still exchanging genes.

What was believed, and is not

A page on this organism has to carry its corrections out loud, because the description most doctors learned is now wrong in at least four places. The cancer is no longer mainly squamous. The parasite was never the largest exposure in the population where it was studied best. The phenotype everyone attributed to it turns up in a country that has never had it. One widely quoted nitrosamine measurement that was benchmarked against schistosomiasis patients — a ranitidine dosing study in ten healthy volunteers — has been withdrawn from the literature altogether, and the cards below name each correction with the study that made it.

None of this demotes the organism. Each correction tightens what can honestly be claimed: that this is a classified human carcinogen whose effect runs through decades of inflammation in company with bacteria, chemistry and tobacco, and whose measured contribution to bladder cancer in the one population studied carefully was about one case in six ^14,15,42. A reader who takes only the headline away will overstate the parasite; a reader who takes only the corrections away will dismiss it. Both readings are available in the literature, and both are wrong.

What is still unknown

The largest hole is also the most practical: nobody has shown that treating the parasite reduces bladder cancer. The Egyptian evidence for the histology shift is institutional case mix over time, from single referral centers, and the attribution to control programs is the authors' own inference rather than a measured population effect ^13,21. The study that would settle it — age-standardized bladder cancer incidence and histology from a population-based registry, set against documented mass drug administration coverage — has not been published. And there is a contrary historical datapoint to explain: in 1987 an Egyptian pathologist reported that in Fayoum Province schistosomiasis was falling while bladder cancer was rising ³⁰.

Nor is it known whether cure reverses anything in a person who already has the changes. No cohort or trial has followed treated against untreated people to a cancer endpoint, and no study establishes whether keratinizing squamous metaplasia regresses after the worms are gone. Latency is equally unmeasured: the only quantitative handle is the Alexandria finding of higher risk with first diagnosis before age 15 and with 35 or more years since diagnosis, which is consistent with decades but is an inference from a case-control study, not a measured interval ¹⁴. The one molecular look at what treatment does to the tissue found the opposite of reassurance: in cervical samples from 39 Tanzanian women, cancer-associated gene expression was present during infection and more marked four to twelve months after praziquantel had cleared it, which the authors read as a possible short-term rise in risk rather than a reversal, and flag for confirmation ⁴⁷.

Mechanistically, the field says so itself. A 2020 paper from the leading laboratory called the mechanisms largely unknown and blamed a historical lack of animal models ²⁸; a 2019 genome paper for this species said little is known at the molecular level about the fluke or its disease ²⁷; a 2017 clinical review said the mechanisms remain poorly understood for want of a convenient animal model ⁴⁰; and a 2022 review of the squamous subtype noted that studies focused on it remain scarce ¹¹. The direction of the IPSE effect on bacterial co-infection is unresolved ³⁵, and the catechol-estrogen work has never been linked to a measured cancer outcome in a person ^32,33.

Two further gaps belong on the record. The global burden figures disagree with each other across sources — at least 230 million infected for the genus ⁴, about 110 million for this species ⁵, 210 million in 76 countries as of 2009 ⁶, roughly 250 million in the WHO guideline review ⁷ and more than 290 million threatened on another WHO figure ⁷¹ — and a modeled age-standardized prevalence of 1,914 per 100,000 for 2021 (95% uncertainty interval 1,379–2,511), falling since 1990 ⁸. The figures disagree by method as much as by source: a 2025 comparison co-authored by the World Health Organization’s global neglected tropical diseases program set Global Burden of Disease estimates against China’s own reported data for 2004 to 2020 and found the model about 1.5-fold high for schistosomiasis, and far higher for other neglected diseases — so any single number should be quoted with its source, its year and its method ⁷⁷. And female genital schistosomiasis has no diagnostic reference standard, no agreed screening method, no reliable burden estimate and no WHO guideline, which is why its prevalence figures should be read as indicative rather than measured ^48,62.

How it fits the season's question

The season asks whether the cancers attributed to parasites are the real number or only the number someone has looked for. This organism is the strongest case the affirmative has, and reading it carefully shows how much work the looking does. The classification is sound: IARC placed it in Group 1 in 1994 and still lists it among 12 Group 1 infectious agents in a 2026 analysis ^9,10,11. The pattern that earned it that place — young male patients, squamous histology, geographic correlation — was visible to a Cairo pathologist in 1911 ⁴⁰.

But the number attached to it has always depended on a method that misses. The historical share of bladder cancers called schistosomal came from finding eggs in tissue, and the pathologists who used that method now say it is unreliable ⁴¹. The population estimates come from finding eggs in urine, and one sample finds about 61% of infections ⁵⁶. If the detection is that leaky, the attributed count can be wrong in either direction: tumors in people whose infection was never confirmed were counted as non-schistosomal, and tumors in infected people were counted as caused when the Egyptian data show heavily infected and egg-negative tumors looking the same ³⁰.

What the careful numbers support is narrower than the folklore and more interesting. The individual risk measured with adjustment is about 1.7-fold and one case in six, against 6.6-fold and about three in four of the male cases for tobacco in the same city ^14,15. The mouse experiment that comes closest to a causal test needed a chemical nitrosamine alongside the eggs ⁵⁵. The country with no parasite at all shows the same squamous cancer arising from ordinary chronic urinary infection at an odds ratio above 11 ⁴². Taken together, the best current reading is that S. haematobium is a real and classified human carcinogen that works mostly by keeping a bladder inflamed for decades, in company with bacteria, chemistry and tobacco — and that the honest answer to the season's question here is that the attributed number was never precise enough to be either confirmed or dismissed.

The practical corollary is clinical, and it cuts both ways. A patient from an endemic region with bladder cancer today is more likely to have urothelial than squamous carcinoma ^13,41, which matters because immune checkpoint drugs transformed the care of urothelial carcinoma while bladder cancers of other cell types, squamous among them, are generally left out of those trials and approvals ¹¹. And a migrant or traveler with unexplained hematuria deserves a test chosen knowing its sensitivity: serum or urine DNA amplification rather than a single urine microscopy, because the single microscopy is the test most likely to send them away reassured and still infected ^56,58.

Where it connects

Sources

77 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Buonfrate D, Ferrari TCA, Adegnika AA, Russell Stothard J, Gobbi FG. Human schistosomiasis.Lancet · 2025 · 405(10479):658-670doi:10.1016/S0140-6736(24)02814-9 · PMID 39986748

   The current authoritative clinical review: transmission through skin, the two chronic patterns by species, and squamous-cell carcinoma of the bladder as the recognized cancer complication of the urogenital form. It states that egg-based diagnosis may have low sensitivity; it contains no effect estimates.

2. 2
   Savassi BAES, Mouahid G, Lasica C, et al. Cattle as natural host for Schistosoma haematobium (Bilharz, 1852) Weinland, 1858 x Schistosoma bovis Sonsino, 1876 interactions, with new cercarial emergence and genetic patterns.Parasitol Res · 2020 · 119(7):2189-2205doi:10.1007/s00436-020-06709-0 · PMID 32468189

   Used here for two things: the species authority as current taxonomy writes it, dated 1852, and the demonstration of cattle as a reservoir for both the cattle species and human-infective hybrids in Benin. It does not address cancer.

3. 3
   Li H, Chen Y, Zhu Y, et al. Exploring the immune interactions between Oncomelania hupensis and Schistosoma japonicum, with a cross-comparison of immunological research progress in other intermediate host snails.Parasit Vectors · 2023 · 16(1):453doi:10.1186/s13071-023-06011-9 · PMID 38093363

   Names the three globally significant snail intermediate hosts by species and frames snail control as the way to break the life cycle. A review of snail immunology, not of human disease.

4. 4
   Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis.Lancet · 2014 · 383(9936):2253-2264doi:10.1016/S0140-6736(13)61949-2 · PMID 24698483

   Establishes the central premise that trapped eggs, not adult worms, drive disease through a granulomatous response, and gives the conservative figure of at least 230 million people infected. A review, not primary data.

5. 5
   Mertelsmann AM, Bowers SF, Wright D, et al. Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.PLoS Negl Trop Dis · 2024 · 18(9):e0012456doi:10.1371/journal.pntd.0012456 · PMID 39250522

   A PRISMA-registered review of 94 studies from 3,177 screened: about 110 million people affected, a predominantly type 2 immune phenotype, raised metalloproteinase expression, upregulated p53 and BCL2, microbiome disturbance, and the authors' conclusion that the parasite promotes cellular transformation with oncogenic potential. Human, animal and ex vivo evidence are pooled.

6. 6
   Berriman M, Haas BJ, LoVerde PT, et al. The genome of the blood fluke Schistosoma mansoni.Nature · 2009 · 460(7253):352-358doi:10.1038/nature08160 · PMID 19606141

   The first flatworm genome: 363 megabases, at least 11,809 genes, more than 300 proteases, and lipid metabolism deficits that make the worm host-dependent. Its burden figure of 210 million in 76 countries is an estimate from 2009 for schistosomiasis as a whole.

7. 7
   Lo NC, Bezerra FSM, Colley DG, et al. Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.Lancet Infect Dis · 2022 · 22(11):e327-e335doi:10.1016/S1473-3099(22)00221-3 · PMID 35594896

   The guideline development group's own summary of the February 2022 WHO recommendations: preventive chemotherapy extended from school-aged children to all age groups from two years upward, a lower prevalence threshold for annual treatment, and more frequent treatment, against a background figure of about 250 million people infected. A review of policy, not new evidence.

8. 8
   Lv C, Chen Y, Cheng Z, et al. Global burden of zoonotic infectious diseases of poverty, 1990–2021.Infect Dis Poverty · 2024 · 13(1):82doi:10.1186/s40249-024-01252-x · PMID 39506825

   The current modeled burden from Global Burden of Disease 2021: schistosomiasis has the highest age-standardized prevalence rate of the zoonotic diseases of poverty at 1,914.3 per 100,000 (95% uncertainty interval 1,378.9–2,510.9) and an age-standardized disability-adjusted life-year rate of 21.9, both falling since 1990. A model fitted to surveillance data, not a count of people.

9. 9
   IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Schistosomes, liver flukes and Helicobacter pylori.IARC Monogr Eval Carcinog Risks Hum · 1994 · 61:1-241PMID 7715068

   The primary record for the 1994 volume, which runs 241 pages. The record carries no abstract and no meeting dates, so the group assignments cannot be read off it and are taken here from peer-reviewed papers that restate them.

10. 10
    Rumgay H, Georges D, Huang Y, et al. Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.Lancet Oncol · 2026 · 27(10):1237-1248doi:10.1016/S1470-2045(26)00307-4 · PMID 42805198

    IARC's own current burden analysis, naming exactly 12 Group 1 infectious agents including S. haematobium, with 2.3 million infection-attributable cancers in 2024, or 12% of all cases. It does not break out a number for this parasite in its abstract. Funding stated as none.

11. 11
    Madureira AC. Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma.Front Immunol · 2022 · 13:955000doi:10.3389/fimmu.2022.955000 · PMID 36148227

    Source for the Group 1 date of 1994 and for squamous carcinoma accounting for 53-69% of bladder carcinomas in endemic regions, and for the clinical consequence that divergent histologies are generally ineligible for checkpoint therapy. A single-author mini-review; the 53-69% range is cited from earlier literature rather than generated here.

12. 12
    Yohana C, Bakuza JS, Kinung'hi SM, Nyundo BA, Rambau PF. The trend of schistosomiasis related bladder cancer in the lake zone, Tanzania: a retrospective review over 10 years period.Infect Agent Cancer · 2023 · 18(1):10doi:10.1186/s13027-023-00491-1 · PMID 36800971

    The check on whether the Egyptian reversal is general: squamous carcinoma still 57.0% of 481 bladder cancers, transitional-cell 37.6% and adenocarcinoma 5.4%, with eggs in 25.2% of specimens and associated with squamous type (p = 0.001), mean age 55. A single referral pathology department, retrospective, with no population denominator, and infection judged by eggs in the specimen — the same insensitive method this page criticizes elsewhere.

13. 13
    Gouda I, Mokhtar N, Bilal D, El-Bolkainy T, El-Bolkainy NM. Bilharziasis and bladder cancer: a time trend analysis of 9843 patients.J Egypt Natl Canc Inst · 2007 · 19(2):158-162PMID 19034337

    The largest dataset documenting the histological reversal, with egg positivity, median age and sex ratio moving alongside it. A single tertiary institute across 37 years, so referral and diagnostic practice changed with the biology; no DOI; schistosomiasis judged by egg positivity in the specimen, which is insensitive.

14. 14
    Bedwani R, Renganathan E, El Kwhsky F, et al. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt.Br J Cancer · 1998 · 77(7):1186-1189doi:10.1038/bjc.1998.197 · PMID 9569060

    The best-adjusted measurement of individual risk: odds ratio 1.72 (95% CI 1.0-2.9), about 16% of cases, with higher risk for early first diagnosis and long time since diagnosis. Exposure is self-reported clinical history rather than parasitological confirmation, and controls were hospital-based.

15. 15
    Bedwani R, el-Khwsky F, Renganathan E, et al. Epidemiology of bladder cancer in Alexandria, Egypt: tobacco smoking.Int J Cancer · 1997 · 73(1):64-67doi:10.1002/(sici)1097-0215(19970926)73:1<64::aid-ijc11>3.0.co;2-5 · PMID 9334811

    The companion analysis in the same population: current smoking odds ratio 6.6 (95% CI 3.1-13.9), rising to 16.5 with more than 40 years of smoking, explaining about 75% of male cases. Smoking prevalence was very low in women, so tobacco was not a relevant risk factor for female bladder cancer there.

16. 16
    Zwang J, Olliaro PL. Clinical efficacy and tolerability of praziquantel for intestinal and urinary schistosomiasis-a meta-analysis of comparative and non-comparative clinical trials.PLoS Negl Trop Dis · 2014 · 8(11):e3286doi:10.1371/journal.pntd.0003286 · PMID 25412105

    The honest numbers on the only drug, from 55 trials and 19,499 subjects given praziquantel, a comparator or placebo, with cure rate assessed in 17,017 and tolerability in 12,435: cure rate 77.1% (95% CI 68.4-85.1) for S. haematobium and 63.5% for mixed infections at 40 mg/kg, egg reduction 94.1%, and an adverse event in 56.9% of those treated. The authors concede that efficacy may be lower than expected at some sites and that the test of cure is imperfect, which flatters the drug. The second author is affiliated with the WHO-hosted program whose dose the paper endorses.

17. 17
    N'Goran EK, Odiere MR, Assandé Aka R, et al. Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.Lancet Infect Dis · 2023 · 23(7):867-876doi:10.1016/S1473-3099(23)00048-8 · PMID 36893784

    The pediatric formulation's pivotal trial: 288 children enrolled from 2,663 prescreened. The cure rates of 87.8% (95% CI 79.6-93.5) on arpraziquantel against 81.3% (95% CI 67.4-91.1) on praziquantel come from cohort 1 alone — 150 children aged 4 to 6 infected with S. mansoni, the trial's only randomized comparison. The 90 children with S. haematobium were in single-arm cohorts, one of them dosed at 60 mg/kg, so no cure rate is reported for this species. Abdominal pain occurred in 14% of all 288 and no safety concerns were identified. Open-label and only partly randomized, and funded in part by the healthcare business of Merck KGaA.

18. 18
    Skelly PJ, Alan Wilson R. Making sense of the schistosome surface.Adv Parasitol · 2006 · 63:185-284doi:10.1016/S0065-308X(06)63003-0 · PMID 17134654

    The tegument as a syncytial cytoplasmic layer covering the whole worm, overlain by a membrane-like secretion with which host molecules associate, and the basis of decades-long survival in the bloodstream. A review of surface biology.

19. 19
    von Bülow V, Lichtenberger J, Grevelding CG, Falcone FH, Roeb E, Roderfeld M. Does Schistosoma mansoni Facilitate Carcinogenesis?Cells · 2021 · 10(8):1982doi:10.3390/cells10081982 · PMID 34440754

    States the classification explicitly: only S. haematobium is Group 1, S. mansoni is Group 3 indicating insufficient evidence. The same authors argue that case reports, animal models and cell culture point toward a real hepatic and colorectal effect, so this is a review by a group with a stake in its own hypothesis.

20. 20
    Felix AS, Soliman AS, Khaled H, et al. The changing patterns of bladder cancer in Egypt over the past 26 years.Cancer Causes Control · 2008 · 19(4):421-429doi:10.1007/s10552-007-9104-7 · PMID 18188671

    The reversal as a single effect estimate: odds ratio 6.00 (95% CI 4.00-8.97) for transitional cell carcinoma in 2005 against 1980. Retrospective record abstraction from one institute, with the limits that carries for how infection was ascertained.

21. 21
    Salem HK, Mahfouz S. Changing patterns (age, incidence, and pathologic types) of schistosoma-associated bladder cancer in Egypt in the past decade.Urology · 2011 · 79(2):379-383doi:10.1016/j.urology.2011.08.072 · PMID 22112287

    An independent Cairo hospital and a different decade showing the same inversion in 1,932 patients, with mean age rising from 41 to 52. Before-and-after proportions only: no adjusted estimates and no p-values in the abstract.

22. 22
    Panzner U, Boissier J. Natural Intra- and Interclade Human Hybrid Schistosomes in Africa with Considerations on Prevention through Vaccination.Microorganisms · 2021 · 9(7):1465doi:10.3390/microorganisms9071465 · PMID 34361901

    The hybridization picture: schistosomes affecting people in 76 countries, human hybrids clustering in the Senegal River Basin, and pure S. bovis plus human-infective hybrids observed in Corsica, alongside the vaccine candidates in advanced preclinical and clinical stages. A review of confirmed hybrid records, so its geography reflects where people have looked.

23. 23
    Ahmed NS, Mahmoud SF, Mohamed ER, Khalifa RM. Histopathological analysis of Schistosoma haematobium metaplasia of the urinary bladder.J Egypt Soc Parasitol · 2017 · 47(1):211-218PMID 30157350

    The concrete pathology: squamous metaplasia in 38 of 54 biopsies, keratinizing in 18, invasive squamous carcinoma in 11. A single-center referral series of 54 patients with no comparison group, in a journal with no DOI, and the metaplasia subtypes showed no statistically significant relation to any variable measured, so the proportions describe the series and not a population.

24. 24
    Kjetland EF, Ndhlovu PD, Gomo E, et al. Association between genital schistosomiasis and HIV in rural Zimbabwean women.AIDS · 2006 · 20(4):593-600doi:10.1097/01.aids.0000210614.45212.0a · PMID 16470124

    The primary human association between female genital schistosomiasis and HIV: 41% versus 26% HIV prevalence among permanent residents, odds ratio 2.1 (95% CI 1.2-3.5), adjusted 2.9 (95% CI 1.11-7.5), and all seven incident HIV cases with baseline signs of the parasite. Cross-sectional with a one-year follow-up; the authors state that prospective studies are needed to confirm it.

25. 25
    Habib MR. Snail immunity to schistosomes: insights from omics studies.Dev Comp Immunol · 2026 · 183:105711doi:10.1016/j.dci.2026.105711 · PMID 42600959

    Used here for the snail half of the life cycle: outcomes across Biomphalaria, Bulinus and Oncomelania range from full resistance to high compatibility, and the divergence is set in a window of 12 to 48 hours after penetration, according to whether the invading miracidia are eliminated or go on to develop sporocysts. A review of omics work in snails, not a life-cycle description written for clinicians.

26. 26
    Pennance T, Rollinson D. Accelerating snail vector genomics.Infect Dis Poverty · 2024 · 13(1):32doi:10.1186/s40249-024-01199-z · PMID 38711151

    A letter, not primary data: it records that genomes for Bulinus, Biomphalaria and Oncomelania are now all in the public domain, including the first African snail vectors and a chromosome-level Oncomelania hupensis assembly, and argues this is what new transmission-control targets will come from.

27. 27
    Stroehlein AJ, Korhonen PK, Chong TM, et al. High-quality Schistosoma haematobium genome achieved by single-molecule and long-range sequencing.Gigascience · 2019 · 8(9):giz108doi:10.1093/gigascience/giz108 · PMID 31494670

    The genome resource for this species, with its authors' own statement that little is known at the molecular level about the fluke or the pathogenesis of its disease, and the figure of more than 100 million people affected. Genomic work; no clinical findings.

28. 28
    Mbanefo EC, Fu CL, Ho CP, Le L, Ishida K, Hammam O, Hsieh MH. Interleukin-4 Signaling Plays a Major Role in Urogenital Schistosomiasis-Associated Bladder Pathogenesis.Infect Immun · 2020 · 88(3):e00669-19doi:10.1128/IAI.00669-19 · PMID 31843965

    Places the pathology in the host's type-2 immune response: knockouts had weaker granulomas and none of the urothelial proliferation or hyper-diploidy seen in normal mice, and interleukin-4 shifted urothelial cell cycle and AKT phosphorylation directly. Also the source for the candid statement that mechanisms were largely unknown as of 2020 for want of animal models. Direction and significance only; no effect sizes in the abstract.

29. 29
    Mostafa MH, Sheweita SA, O'Connor PJ. Relationship between schistosomiasis and bladder cancer.Clin Microbiol Rev · 1999 · 12(1):97-111doi:10.1128/CMR.12.1.97 · PMID 9880476

    The canonical account of the whole proposed mechanism chain, including high urinary N-nitroso compounds in patients, nitrosating bacteria at higher infection intensity, enzyme changes, oxygen radicals and measured alkylation damage with deficient repair. A 1999 review synthesizing human association data and animal experiments; it demonstrates no causation in humans and reports no 8-oxo-dG measurement.

30. 30
    Tawfik HN. Carcinoma of the urinary bladder associated with schistosomiasis in Egypt: the possible causal relationship.Princess Takamatsu Symp · 1987 · 18:197-209PMID 3147281

    The primary source for the bacterial mechanism — nitrate reductase and beta-glucuronidase as bacterial products — and for two early warnings: tumors in heavily infected and egg-negative patients looked alike, and in Fayoum Province schistosomiasis was falling while bladder cancer rose. A 1987 symposium volume with no DOI, whose vitamin A and tryptophan mechanisms are asserted rather than demonstrated.

31. 31
    Gentile JM, Brown S, Aardema M, Clark D, Blankespoor H. Modified mutagen metabolism in Schistosoma hematobium-infested organisms.Arch Environ Health · 1985 · 40(1):5-12doi:10.1080/00039896.1985.10545881 · PMID 3922319

    The actual beta-glucuronidase experiment: infected hamsters had raised serum and urinary enzyme activity, and their urine concentrates enhanced a chemical's mutagenicity in a bacterial assay more than control urine. The urine was not mutagenic on its own, and no effect sizes are reported.

32. 32
    Santos J, Gouveia MJ, Vale N, et al. Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.PLoS One · 2014 · 9(5):e96774doi:10.1371/journal.pone.0096774 · PMID 24848950

    The human measurement behind the catechol-estrogen mechanism: adducts associated with infection at odds ratio 3.35 (95% CI 2.32-4.84) in 93 participants, and with self-reported infertility at 4.33 (95% CI 1.13-16.70). The measured outcome is self-reported infertility, not cancer, and the infertility interval is very wide on a small sample.

33. 33
    Gouveia MJ, Santos J, Brindley PJ, et al. Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer.Cancer Lett · 2015 · 359(2):226-232doi:10.1016/j.canlet.2015.01.018 · PMID 25615421

    Mass spectrometry on urine from 40 Angolans with urogenital schistosomiasis, half with carcinoma: seven estrogen-like metabolites specific to cases, catechol estrogen quinones and quinone-DNA adducts, and products derived from 8-oxo-dG in all 40. Cross-sectional biomarker work; the in vitro tumor-like phenotypes it cites are reported as in vitro.

34. 34
    Pennington LF, Alouffi A, Mbanefo EC, Ray D, Heery DM, Jardetzky TS, Hsieh MH, Falcone FH. H-IPSE Is a Pathogen-Secreted Host Nucleus-Infiltrating Protein (Infiltrin) Expressed Exclusively by the Schistosoma haematobium Egg Stage.Infect Immun · 2017 · 85(12):e00301-17doi:10.1128/IAI.00301-17 · PMID 28923894

    Shows that two IPSE paralogs are made only by eggs and mature female worms, infiltrate cultured human bladder cells, and are carried to the nucleus by specific localization sequences. In vitro work on a cell line; it establishes capability, not a disease effect.

35. 35
    Mbanefo EC, Le L, Pennington LF, et al. IPSE, a urogenital parasite-derived immunomodulatory molecule, suppresses bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection.Parasit Vectors · 2020 · 13(1):615doi:10.1186/s13071-020-04490-8 · PMID 33298153

    The test of IPSE as the factor behind bacterial co-infection, and the result went the other way: no change in urine bacterial counts, and significantly less infection-induced bladder pathology and antimicrobial peptide expression. A mouse experiment with recombinant protein given intravenously, so its bearing on natural infection is indirect.

36. 36
    Shaw ME, Elder PA, Abbas A, Knowles MA. Partial allelotype of schistosomiasis-associated bladder cancer.Int J Cancer · 1999 · 80(5):656-661doi:10.1002/(sici)1097-0215(19990301)80:5<656::aid-ijc4>3.0.co;2-a · PMID 10048962

    Seventy Egyptian tumors with loss of heterozygosity most often at 9p (65%) and 17p (58%), and 17p loss commoner in urothelial than squamous tumors. It describes a genomic pattern distinct from UK and US urothelial cancer; it does not show what caused the losses.

37. 37
    Khaled HM, Bahnassi AA, Zekri AN, Kassem HA, Mokhtar N. Correlation between p53 mutations and HPV in bilharzial bladder cancer.Urol Oncol · 2003 · 21(5):334-341doi:10.1016/s1078-1439(03)00014-0 · PMID 14670539

    In 99 Egyptian bilharzial bladder cancers, p53 was mutated in 33.3% and overexpressed in 35.6%, and HPV DNA was found in 48.97%, mostly type 16; the authors read the mutational spectrum as different from Western bladder cancer. An association study in tumor tissue, which cannot date the exposure that caused the mutations.

38. 38
    Habuchi T, Takahashi R, Yamada H, et al. Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer.Cancer Res · 1993 · 53(16):3795-3799PMID 8339293

    An early mutation-spectrum comparison: p53 mutations in 20 of 61 Japanese urothelial cancers (33%) and 6 of 7 Egyptian schistosomal bladder cancers, with every base substitution in squamous tumors falling at G:C sites. Seven Egyptian cases is a very small series, and the authors found no mutation pattern specific to the squamous tumors beyond that.

39. 39
    Tan SY, Ahana A. Theodor Bilharz (1825-1862): discoverer of schistosomiasis.Singapore Med J · 2007 · 48(3):184-185PMID 17342284

    A short biographical article whose PubMed record carries the attribution of the discovery and Bilharz's dates but no abstract and no DOI, so nothing beyond the title can be verified from the record.

40. 40
    Berry A, Iriart X, Fillaux J, Magnaval JF. [Urinary schistosomiasis and cancer].Bull Soc Pathol Exot · 2017 · 110(1):68-75doi:10.1007/s13149-017-0547-4 · PMID 28185084

    The historical spine: Goebel's suspicion in 1905, Ferguson's 40 autopsies in Cairo in 1911, confirmation only decades later by adjusted case-control studies, mechanisms poorly understood for want of an animal model, better Egyptian control since 1970, and no verified link to genital organ cancers. A French-language review.

41. 41
    Amin HAA, Kobaisi MH, Samir RM. Schistosomiasis and Bladder Cancer in Egypt: Truths and Myths.Open Access Maced J Med Sci · 2019 · 7(23):4023-4029doi:10.3889/oamjms.2019.857 · PMID 32165946

    The sharpest published statement of the reversal, and the methodological warning that histopathological confirmation of the infection is not accurate. Described as a cross-sectional case-control study, which is internally inconsistent; denominators are not stated in the abstract; the argument against smoking rests on an indirect inference from lung cancer trends.

42. 42
    Pottegård A, Kristensen KB, Friis S, Hallas J, Jensen JB, Nørgaard M. Urinary tract infections and risk of squamous cell carcinoma bladder cancer: A Danish nationwide case-control study.Int J Cancer · 2020 · 146(7):1930-1936doi:10.1002/ijc.32842 · PMID 31863454

    The control experiment done without a parasite: squamous carcinoma odds ratio 11.4 (95% CI 7.6-17.2) with dose-response for heavy use of urinary-infection antibiotics, and no association with urothelial carcinoma. The exposure is a prescription proxy rather than confirmed infection, and the authors had no smoking data, which they addressed with a quantitative bias analysis.

43. 43
    Park SK, Friedrich L, Yahya NA, et al. Mechanism of praziquantel action at a parasitic flatworm ion channel.Sci Transl Med · 2021 · 13(625):eabj5832doi:10.1126/scitranslmed.abj5832 · PMID 34936384

    Resolves, after decades of clinical use, that praziquantel activates a TRPM channel by binding a hydrophobic pocket in its voltage-sensor-like domain, causing calcium entry and paralysis, and that one amino acid change explains why Fasciola is unaffected. Commercial conflict: four co-authors are employed by Merck KGaA or its subsidiaries, which manufacture praziquantel and run the largest donation program for it.

44. 44
    Inaba Y. A cohort study on the causes of death in an endemic area of schistosomiasis japonica in Japan.Ann Acad Med Singap · 1984 · 13(2):142-148PMID 6497313

    The only genuine human cohort in the S. japonicum cancer literature: 2,067 residents followed from 1958 to 1982, with observed-to-expected ratios of 4.05 and 5.53 for liver cirrhosis, 2.30 for liver cancer in men only and 2.25 for colon cancer in women only, rising with years of residence. No confidence intervals, exposure is residence rather than individual infection, and the sex-discordant findings are unexplained.

45. 45
    IARC. Biological agents. Volume 100 B. A review of human carcinogens.IARC Monogr Eval Carcinog Risks Hum · 2012 · 100(Pt B):1-441PMID 23189750

    The 2012 re-review of agents already in Group 1, indexed for schistosomiasis haematobia among others. As with volume 61, the record has no abstract, so it establishes the document and its scope but not the wording of the evaluation.

46. 46
    Sturt AS, Omar T, Hansingo I, Kamfwa P, Bustinduy A, Kelly H. Association of female genital schistosomiasis and human papillomavirus and cervical pre-cancer: a systematic review.BMC Womens Health · 2025 · 25(1):2doi:10.1186/s12905-024-03514-0 · PMID 39754189

    The honest state of the cervical question: six studies, 1,081 women, five cross-sectional and one prospective, risk of bias assessed on a modified Newcastle-Ottawa scale, registered PROSPERO CRD42023389301. Its conclusion is that an association can be neither confirmed nor excluded.

47. 47
    Mertelsmann AM, Maganga JK, Lee MH, et al. Schistosoma haematobium infection is associated with oncogenic gene expression in cervical mucosa, with enhanced effects following treatment: a pilot study.PLoS Negl Trop Dis · 2025 · 19(11):e0013569doi:10.1371/journal.pntd.0013569 · PMID 41270010

    A 39-woman transcriptome pilot in Tanzania, 20 infected and 19 not, sampled before and 4–12 months after praziquantel: 9 genes differentially expressed with versus without infection, 23 after parasitological clearance versus infection, and 29 after clearance versus never infected. Most differentially expressed genes, both during infection and after clearance, were genes reported as raised in cancers. A pilot with no cancer outcome; the authors call for work on whether the post-treatment signal resolves with time.

48. 48
    Ndubani R, Lamberti O, Kildemoes A, et al. The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa.Wellcome Open Res · 2025 · 9:360doi:10.12688/wellcomeopenres.22429.2 · PMID 39170763

    The documented state of the field for female and male genital schistosomiasis: absent awareness, no accurate burden estimates, no standardized screening or diagnosis, and no WHO guidelines to inform practice. A workshop report, not research data.

49. 49
    Gyang VP, Abdulssalam HO, Ahmed AO, et al. Investigating outcomes of female genital schistosomiasis in communities in Ogun State, Nigeria: a pilot cross-sectional study.Trans R Soc Trop Med Hyg · 2025 · 119(4):367-374doi:10.1093/trstmh/traf006 · PMID 39901841

    A current pilot: of 47 women examined by colposcopy using the WHO atlas, 23.4% had egg-patent infection, 38.3% had yellow sandy patches, and all Pap smears showed cervical atypia, with ova in two. Forty-seven consenting women out of 126 screened, so the proportions are indicative and the authors ask for larger studies.

50. 50
    Sturt AS, Randrianasolo B, Downs JA, Jøker K, Mazigo HD, van Lieshout L, Leutscher P. Diagnosis and treatment of female genital schistosomiasis.Lancet Microbe · 2026 · 7(6):101356doi:10.1016/j.lanmic.2026.101356 · PMID 42127951

    The current authority on how the condition is found and treated, and the source of the visual, histological and molecular subtype framework. A narrative review in a commissioned series, not new data.

51. 51
    Lamberti O, Kumwenda D, Kelly H, Kamfwa P, Kayuni SA, Stothard JR, Bustinduy AL. Female genital schistosomiasis, including zoonotic and hybrid schistosomes, and other cervicovaginal co-infections.Lancet Microbe · 2026 · 7(6):101425doi:10.1016/j.lanmic.2026.101425 · PMID 42127952

    The current review of how genital schistosomiasis sits among the human immunodeficiency virus, human papillomavirus, bacterial vaginosis and vulvovaginal candidiasis, and of the hybrid and zoonotic species appearing in it. A review; no effect estimates of its own.

52. 52
    Lamberti O, Kayuni S, Kumwenda D, et al. Female genital schistosomiasis burden and risk factors in two endemic areas in Malawi nested in the Morbidity Operational Research for Bilharziasis Implementation Decisions (MORBID) cross-sectional study.PLoS Negl Trop Dis · 2024 · 18(5):e0012102doi:10.1371/journal.pntd.0012102 · PMID 38718065

    Visual prevalence 26.9% (260/967) and molecular 8.2% (78/942) against egg-patent urinary infection in 6.5% (38/584); molecular disease associated with visual disease (adjusted OR 2.9, 95% CI 1.7–5.0) and with egg-patent infection (adjusted OR 7.5, 95% CI 3.27–17.2). Some villages had high molecular prevalence although under 10% of their schoolchildren had urinary infection. Cross-sectional, and the visual diagnosis carries the reproducibility problem described elsewhere on this page.

53. 53
    Mberu M, Zongo K, Leaning E, Makau-Barasa L, Kamara K, Jacobson J. Female genital schistosomiasis: addressing diagnostic and programmatic gaps to advance elimination efforts.Int J Infect Dis · 2025 · 152:107798doi:10.1016/j.ijid.2025.107798 · PMID 39870160

    Source for the 40–56 million estimate and for the argument that the condition belongs inside elimination frameworks and reproductive health services. A commentary from an implementing organization, so the figure is quoted rather than derived.

54. 54
    Tang F, Liao S, Hou X. Infection-driven bladder carcinogenesis: molecular mechanisms of pathogen-urothelial cell interactions.Pathol Res Pract · 2026 · 283:156488doi:10.1016/j.prp.2026.156488 · PMID 42054810

    The current synthesis of bladder cancer's infectious causes, setting this parasite beside human papillomavirus, uropathogenic Escherichia coli and BK virus, and naming inducible nitric oxide synthase as its proposed route to DNA damage. A narrative review; it generates no data and states its own mechanistic gaps.

55. 55
    Chala B, Choi MH, Moon KC, Kim HS, Kwak C, Hong ST. Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice.Korean J Parasitol · 2017 · 55(1):21-29doi:10.3347/kjp.2017.55.1.21 · PMID 28285503

    The cleanest experimental test of the two-hit model: squamous metaplasia appeared in the eggs-plus-NDMA group (NDMA, N-nitrosodimethylamine) at week 12 and not in other groups, with raised Ki-67 where eggs were combined with a bladder carcinogen. A mouse model with egg injection, not natural infection.

56. 56
    Ndum NC, Ali SM, Ali MN, et al. Evaluation of six different tests for Schistosoma haematobium diagnosis in a near-elimination setting: A prospective observational diagnostic accuracy study.PLoS Negl Trop Dis · 2026 · 20(9):e0014066doi:10.1371/journal.pntd.0014066 · PMID 42743322

    The most current head-to-head comparison, Pemba 2025, against five-day urine filtration as reference: single-sample sensitivity 76.7% for an artificial-intelligence microscopy scanner, 76.0% qPCR, 61.2% single-day filtration, 56.1% recombinase amplification, 44.6% Hemastix and 30.6% antigen assay, with specificity above 92% except for the two molecular tests. A near-elimination setting, so these figures are the low-intensity end of the range. Two authors are employed by the company that makes the scanner.

57. 57
    Ochodo EA, Gopalakrishna G, Spek B, et al. Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.Cochrane Database Syst Rev · 2015 · 2015(3):CD009579doi:10.1002/14651858.CD009579.pub2 · PMID 25758180

    Ninety studies, 88 of them field settings in Africa: microhematuria strips 75% sensitive (95% CI 71-79) and 87% specific against microscopy across 102,447 participants, and the point-of-care circulating cathodic antigen test only 39% sensitive for S. haematobium with a 6-73% interval. Its reference standard is microscopy, which is itself insensitive, and study reporting was poor against current standards.

58. 58
    Cnops L, Soentjens P, Clerinx J, Van Esbroeck M. A Schistosoma haematobium-specific real-time PCR for diagnosis of urogenital schistosomiasis in serum samples of international travelers and migrants.PLoS Negl Trop Dis · 2013 · 7(8):e2413doi:10.1371/journal.pntd.0002413 · PMID 24009791

    The species-specific Dra1 real-time PCR: positive in 22 of 23 serum samples from parasitologically confirmed cases and in every egg-positive urine, stool and biopsy sample, with an analytical sensitivity of half an egg per gram of feces and no cross-reaction with S. mansoni. An evaluation in travelers and migrants, not a population survey.

59. 59
    Knopp S, Corstjens PLAM, Koukounari A, et al. Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings.PLoS Negl Trop Dis · 2015 · 9(5):e0003752doi:10.1371/journal.pntd.0003752 · PMID 25973845

    In Pemba, the laboratory antigen assay found an empirical prevalence of 14% against 5% for quality-controlled microscopy and 4% for strips, with latent-class sensitivity 97% (95% CI 91-100). Sensitivity is estimated by latent class analysis in the absence of a true gold standard, and the samples were frozen for eight months before testing.

60. 60
    Draxl E, Ochodo E, Pillay P, Ndlovu N. Diagnostic accuracy of rapid and point-of-care tests for Schistosoma haematobium in African populations: a systematic review and meta-analysis.Front Parasitol · 2026 · 5:1830789doi:10.3389/fpara.2026.1830789 · PMID 42558930

    Twenty-nine studies and nine point-of-care tests, four pooled: LAMP 94.7% sensitive but 66.4% specific, recombinase amplification 94.1% and 96.6%, serological cassettes about 98% sensitive but needing a centrifuge, and the point-of-care cathodic antigen strip 49.8% sensitive. The authors state that better reference standards are needed before many of these figures can be trusted.

61. 61
    Hamway Y, Josten T, Abdellatif S, et al. Diagnostic accuracy of plasma cell-free DNA qPCR for Schistosoma haematobium assessed by Bayesian latent class analysis in a cohort of pregnant women from Lambaréné, Gabon.Infect Dis Poverty · 2026 · 15(1)doi:10.1186/s40249-026-01447-4 · PMID 42104414

    A 2026 test of parasite DNA in 20 microliters of plasma in 296 pregnant women: positivity 24.3% against 18.6% for urine microscopy, with latent-class sensitivity 74.0% (95% credible interval 57.2-90.8) and microscopy most specific at 94.9%. Agreement between tests was limited, and the accuracy figures come from a model, not a gold standard.

62. 62
    Sturt A, Bristowe H, Webb E, et al. Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review and association with clinical symptoms.Wellcome Open Res · 2023 · 8:14doi:10.12688/wellcomeopenres.18737.2 · PMID 36864924

    The reference standard for female genital schistosomiasis tested against itself: two expert reviewers of the same 527 image sets diagnosed disease in 35.3% (165/468 of the images Reviewer 1 judged interpretable) and 63.6% (265/417 for Reviewer 2), agreeing on a diagnosis for only 38.7% (204/527) of the women, kappa 0.16, which the authors call a call to action for better point-of-care diagnostics. It measures reader agreement, not accuracy against a true standard, because none exists.

63. 63
    Lemin ME, Bustinduy AL, Roberts CH. Visual diagnostics for female genital schistosomiasis and the opportunity for improvement using computer vision.Parasitology · 2025 · 152(14):1520-1531doi:10.1017/S0031182025100826 · PMID 40936174

    A review arguing the case for computer vision in visual diagnosis, and quoting up to 56 million women and girls affected. It proposes an approach; it reports no accuracy figures of its own.

64. 64
    Bustinduy AL, Edielu A, Ayebazibwe GK, et al. Safety and efficacy of praziquantel 40 mg/kg versus 80 mg/kg in preschool-aged children with intestinal schistosomiasis in Uganda: a 2 x 2 factorial, double-blind, placebo-controlled, phase 2 randomised trial.Lancet Glob Health · 2025 · 13(6):e1091-e1100doi:10.1016/S2214-109X(25)00095-6 · PMID 40412398

    Cure at four weeks 67% on 40 mg/kg against 90% on a split 80 mg/kg (absolute difference 23%, 95% CI 14–31; p < 0.001), no difference in adverse events, registered NCT03640377, funded by the US National Institute of Child Health and Human Development. 354 children, S. mansoni and 12–47 months only, and a phase 2 result, so it does not transfer directly to this species.

65. 65
    Kasinathan RS, Sharma LK, Cunningham C, Webb TR, Greenberg RM. Inhibition or knockdown of ABC transporters enhances susceptibility of adult and juvenile schistosomes to Praziquantel.PLoS Negl Trop Dis · 2014 · 8(10):e3265doi:10.1371/journal.pntd.0003265 · PMID 25330312

    The source used here for the drug's hard limit, stated plainly in its abstract: praziquantel is not active against immature mammalian-stage schistosomes, and juveniles three to four weeks post-infection are refractory to 2 micromolar drug until transporter inhibitors are added. It also records field isolates with heritable reductions in susceptibility. Ex vivo worms, not a clinical trial.

66. 66
    Kurscheid J, Buhl A, Westenberg E, Palmeirim MS, Winkler AS, Steinmann P, Monnier N. Considerations and expectations for the administration of dispersible arpraziquantel to young children: a landscape analysis.Int Health · 2025 · 17(4):527-534doi:10.1093/inthealth/ihae092 · PMID 39850987

    Explains why preschool-aged children were left out of mass treatment — operational problems of dosing and administering the standard tablet — and what the dispersible tablet with improved taste and smaller size is meant to fix. A stakeholder landscape analysis, not an efficacy study.

67. 67
    Wiegand RE, Fleming FM, de Vlas SJ, et al. Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections.Lancet Glob Health · 2022 · 10(9):e1355-e1359doi:10.1016/S2214-109X(22)00287-X · PMID 35961358

    Gives the operational definition of elimination as a public health problem — under 1% prevalence of heavy-intensity infections, meaning 50 or more S. haematobium eggs per 10 mL of urine — and argues that the evidence supporting that definition is inadequate as morbidity becomes subtler under large control programs. A viewpoint, not a measurement.

68. 68
    Leta GT, Tasew G, Getachew B, et al. Burden of schistosomiasis in Ethiopia following 10 years of preventive chemotherapy: a national cross-sectional geostatistical survey.Lancet Glob Health · 2026 · 104037doi:10.1016/j.langlo.2026.104037 · PMID 42785339

    The current picture of a national program at the 2030 target: 121,593 children at 4,258 sites between June 2021 and October 2024, S. mansoni by Kato-Katz and S. haematobium by urine filtration and dipstick in three regions, with geostatistical modeling to the subdistrict. Mostly an S. mansoni country, so the S. haematobium figure rests on 26,885 children; funded by the END Fund's Deworming Innovation Fund.

69. 69
    Leija-Montoya AG, González-Ramírez J, Martínez-Coronilla G, et al. Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis.Int J Mol Sci · 2022 · 23(15):8173doi:10.3390/ijms23158173 · PMID 35897749

    The only source retrieved here that places S. japonicum in Group 2B, possibly carcinogenic to humans, in connection with liver and colorectal cancer. A secondary review; the classification is restated, not documented from the monograph.

70. 70
    Paluch M, Cudzik M, Kędra A, et al. Can flukes cause cancer? Insight into molecular links between parasites and carcinogenesis.Mol Biochem Parasitol · 2025 · 264:111707doi:10.1016/j.molbiopara.2025.111707 · PMID 41138780

    The current citation for the full list of six fluke species within IARC's scope. Its abstract names the species but does not state which group each sits in, so it supports "considered" and not "classified".

71. 71
    Weglage J, Wolters F, Hehr L, et al. Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon.Sci Rep · 2020 · 10(1):22373doi:10.1038/s41598-020-79450-4 · PMID 33361772

    The strongest mechanistic case for S. mansoni and colorectal cancer, reaching into human tissue: Wnt/beta-catenin, c-Jun, Cyclin D1 and DNA-damage markers induced in enterocytes and confirmed in biopsies from infected patients. It also carries the WHO figure of more than 290 million people threatened. No cancer outcome was measured in any human.

72. 72
    Shousha HI, Abdelaziz AO, Nabeel MM, et al. Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.Pathog Glob Health · 2021 · 116(2):119-127doi:10.1080/20477724.2021.1975081 · PMID 34494507

    The largest human effect estimate for S. mansoni and any cancer, and it is modest: adjusted odds ratio 1.589 (95% CI 1.187-2.127) for prior infection in 1,446 liver cancer patients, with a lower antiviral response rate as a separate finding. Single center, exposure is a history rather than confirmed current infection, and residual confounding by hepatitis is hard to exclude in this population.

73. 73
    Toda KS, Kikuchi L, Chagas AL, et al. Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review.J Clin Transl Hepatol · 2015 · 3(4):260-264doi:10.14218/JCTH.2015.00027 · PMID 26807381

    Seven Brazilian patients with both liver cancer and S. mansoni infection, five with portal vein thrombosis, four with hepatitis B core antibodies, none with hepatitis C, all of whom died. The authors say it remains unclear whether the parasite alone has carcinogenic potential. A case series with no denominator and no controls — the weakest class of evidence about cause.

74. 74
    Qiu DC, Hubbard AE, Zhong B, Zhang Y, Spear RC. A matched, case-control study of the association between Schistosoma japonicum and liver and colon cancers, in rural China.Ann Trop Med Parasitol · 2005 · 99(1):47-52doi:10.1179/136485905X19883 · PMID 15701255

    The best human effect estimates for S. japonicum: liver cancer odds ratio 3.7 (95% CI 1.0-13) among hepatitis-negative pairs and colon cancer 3.3 (95% CI 1.8-6.1), with attributable fractions of 27% and 24%. Hospital controls, and exposure was partly ascertained by interviewing subjects or relatives, which is a recall-bias problem.

75. 75
    Pan W, Wang W, Huang J, et al. The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer.Jpn J Clin Oncol · 2020 · 50(4):446-455doi:10.1093/jjco/hyz210 · PMID 32297641

    c-MYC amplification in 14.1% of 354 colorectal cancers predicted worse survival in the schistosomal subgroup (P < 0.001) but not the non-schistosomal one (P = 0.155). A prognostic finding in people who already have cancer: it says nothing about whether the parasite caused it, and a subgroup multivariate P of 0.046 in a retrospective tissue-microarray study is fragile.

76. 76
    Zeng T, Mitch WA. Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine. [RETRACTED]Carcinogenesis · 2016 · 37(6):625-634 — flagged in PubMed as a retracted publicationdoi:10.1093/carcin/bgw034 · PMID 26992900

    Cited here only as a retraction. The paper claimed a 400-fold rise in 24-hour urinary NDMA, from 110 to 47,600 nanograms, in ten volunteers, and benchmarked those rates against patients with schistosomiasis. Its PubMed record carries the Retracted Publication type, so neither the numbers nor the comparison stand as evidence.

77. 77
    Yang GJ, Ouyang HQ, Zhao ZY, Li WH, Fall IS, Djirmay AG, Zhou XN. Discrepancies in neglected tropical diseases burden estimates in China: comparative study of real-world data and Global Burden of Disease 2021 data (2004–2020).BMJ · 2025 · 388:e080969doi:10.1136/bmj-2024-080969 · PMID 39965820

    Two staff of the World Health Organization's global neglected tropical diseases program are co-authors. The ratio of the Global Burden of Disease estimate to reported-data disability-adjusted life years was 1.5 for schistosomiasis, 11 for echinococcosis, 17 for leprosy and 280 for visceral leishmaniasis. One country, and reported data undercount in their own way, so this bounds the disagreement rather than resolving it.