Antibody response to malaria vaccine candidates in pregnant women with Plasmodium falciparum and Schistosoma haematobium infections.

Malaria in pregnancy has severe consequences for the mother and foetus. Antibody response to specific malaria vaccine candidates (MVC) has been associated with a decreased risk of clinical malaria and its outcomes. We studied Plasmodium falciparum (Pf) and Schistosoma haematobium (Sh) infections and factors that could influence antibody responses to MVC in pregnant women. A total of 337 pregnant women receiving antenatal care (ANC) and 139 for delivery participated in this study. Pf infection was detected by qPCR and Sh infection using urine filtration method. Antibody levels against CSP, AMA-1, GLURP-R0, VAR2CSA and Pfs48/45 MVC were quantified by ELISA. Multivariable linear regression models identified factors associated with the modulation of antibody responses. The prevalence of Pf and Sh infections was 27% and 4% at ANC and 7% and 4% at delivery. Pf infection, residing in Adidome and multigravidae were positively associated with specific IgG response to CSP, AMA-1, GLURP-R0 and VAR2CSA. ITN use and IPTp were negatively associated with specific IgG response to GLURP-R0 and Pfs48/45. There was no association between Sh infection and antibody response to MVC at ANC or delivery. Pf infections in pregnant women were positively associated with antibody response to CSP, GLURP-R0 and AMA-1. Antibody response to GLURP-R0 and Pfs48/45 was low for IPTp and ITN users. This could indicate a lower exposure to Pf infection and low malaria prevalence observed at delivery.

Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants.

OBJECTIVE: Schistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count. RESULTS: Of the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone.

Urinogenital schistosomiasis knowledge, attitude, practices, and its clinical correlates among communities along water bodies in the Kwahu Afram Plains North District, Ghana.

BACKGROUND: Adequate knowledge and proper practices coupled with knowledge of the burden of disease are necessary for the eradication of Schistosoma infection. This study assessed knowledge, attitude, and practice (KAP) as well as health outcomes related to Schistosoma haematobium infection at Kwahu Afram Plains North District (KAPND). METHODS: A cross-sectional survey using a structured questionnaire was carried out among 140 participants from four local communities in KAPND in August 2021. From these participants, 10ml of urine was collected for determination of the presence of S. haematobium and urine routine examination. In addition, 4ml of blood was collected and used for haematological examination. Descriptive statistics and logistic regression analysis using IBM SPSS were used to describe and represent the data collected. RESULTS: The study reports a gap in knowledge about schistosomiasis in the study area with the majority indicating that they have not heard of schistosomiasis (60.7%), do not know the mode of transmission (49.3%), and do not know how the disease could be spread (51.5%). The overall prevalence of urinary schistosomiasis was 52.9%. This was associated with age, occupation, perceived mode of Schistosoma transmission, knowledge of Schistosoma prevention, awareness that schistosomiasis can be treated, frequency of visits to water bodies, and water usage patterns. In multivariate analysis, factors that remained significantly associated with S. haematobium infection were age 21-40 (OR = 0.21, 95% CI: 0.06-0.76), 41-60 (OR = 0.01, 95% CI: 0.01-0.52) and ≥ 60 (OR = 0.02, 95% CI: 0.02-0.87), informal employment (OR = 0.01, 95% CI: 0.01-0.69) and awareness of transmission by drinking water from river body (OR = 0.03, 95% CI: 0.03-0.92). In Schistosoma infection, reduced haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, lymphocytes and eosinophils were observed. White blood cells, neutrophils, and monocytes were significantly elevated in infected states. Urine analysis revealed high pus cells and red blood cells counts among Schistosoma-positive participants. CONCLUSION: Schistosoma infection is endemic among inhabitants in KAPND, and is associated with a gap in knowledge, awareness, and practice possibly due to inadequate education in the area. Poor clinical outcomes associated with Schistosoma infection have been demonstrated in the area. A well-structured public education, nutritional intervention, and mass drug administration will be necessary to eradicate this menace.

The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa.

OBJECTIVES/PURPOSES OF THE STUDY: This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas. METHODS: In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews. RESULTS: Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%). CONCLUSIONS: Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.

Schistosoma haematobium urinary tract complications in African migrants attending primary care facilities in Paris, France: A retrospective cohort study (2004-2018).

OBJECTIVES: Little is known about the burden of urogenital schistosomiasis (UGS) outside endemic areas. This study was aimed at describing urinary complications of UGS detected among African migrants in French primary care facilities. PATIENTS AND METHODS: A retrospective cohort study included patients with UGS diagnosed from 2004 to 2018 in 5 primary health centers in Paris. Cases were defined by the presence of typical Schistosoma haematobium eggs at urine microscopy. Demographic, clinical, biological and imaging data were collected. Ultrasonography (U-S) findings were classified in accordance with the WHO guidelines. RESULTS: U-S was prescribed for all patients and performed in 100/118. Sex ratio (F/M) was 2/98, and mean age 24.4 years. Patients were from West Africa (73% from Mali) and consulted 8 months (median) after their arrival. Among the 95 patients with interpretable findings, 32 (33.7%) had abnormalities related to UGS, considered as major in 6 cases (6.3%), and mostly localized at the bladder (31/32) without detection of cancer. No sociodemographic, clinical, or biological factors were found to be associated with U-S abnormalities. All 100 patients were treated by praziquantel (PZQ). Among those with abnormalities, 20/32 received two to four doses at various time intervals. Post-cure imaging control performed in 19/32 showed persistent abnormalities in 6 patients, on average 5 months after the last PZQ uptake. CONCLUSION: Urinary tract abnormalities associated with UGS were common and predominated at the bladder. U-S should be prescribed to any patient with positive urine microscopy. Schedules for PZQ uptake and U-S monitoring for patients with complications remain to be determined.

A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

BACKGROUND: Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. METHODS: Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. RESULTS: Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. CONCLUSIONS: Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

Detection of cytological abnormalities in urothelial cells from individuals previously exposed or currently infected with Schistosoma haematobium.

Urinary schistosomiasis has long been associated with bladder cancer, but it is still not clear the mechanisms involved. Schistosoma haematobium causes injury and disruptions in the integrity of the urothelium. The cellular and immunologic responses to the infection lead to the formation of granulomata. The ability to use cellular morphological changes to predict the risk of developing bladder cancer following S. haematobium infection is thus important. This study assessed the cellular changes in the urine associated with schistosomiasis and the potential of routine urine being used as a risk predictor of the development of bladder cancer. Urine samples (160) were screened for the presence of S. haematobium ova. Smears stained with the Papanicolaou method were evaluated using light microscopy to determine the cell populations. A high prevalence (39.9%) of urinary schistosomiasis and haematuria (46.9%) was found among the participants. Polymorphonuclear cells, normal and reactive urothelial cells and lymphocytes were characteristic of S. haematobium infection. Squamous metaplastic cells (SMCs) were found in 48% and 47.1% of participants who have had past or current S. haematobium infection respectively, but were not found in participants who had no exposure to S. haematobium. These squamous metaplastic cells are in transition and are prone to malignant transformation when exposed to a carcinogenic agent. There is still a high burden of schistosomiasis in endemic communities in Ghana. by examining urine, one can find metaplastic cells and? dysplastic cells and thus predict cancer in SH-infested patients. Thus, routine urine cytology as a tool to monitor the risk of bladder cancer development is recommended.

Effectiveness of antimalarial drug combinations in treating concomitant urogenital schistosomiasis in malaria patients in Lambaréné, Gabon: A non-randomised event-monitoring study.

BACKGROUND: Urogenital schistosomiasis is prevalent in many malaria endemic regions of sub-Saharan Africa and can lead to long-term health consequences if untreated. Antimalarial drugs used to treat uncomplicated malaria have shown to exert some activity against Schistosoma haematobium. Here, we explore the efficacy on concomitant urogenital schistosomiasis of first-line recommended artemisinin-based combination therapies (ACTs) and investigational second-generation ACTs when administered for the treatment of uncomplicated malaria in Gabon. METHODS: Microscopic determination of urogenital schistosomiasis was performed from urine samples collected from patients with confirmed uncomplicated malaria. Egg excretion reduction rate and cure rate were determined at 4-weeks and 6-weeks post-treatment with either artesunate-pyronaridine, artemether-lumefantrine, artesunate-amodiaquine or artefenomel-ferroquine. RESULTS: Fifty-two (16%) out of 322 malaria patients were co-infected with urogenital schistosomiasis and were treated with antimalarial drug combinations. Schistosoma haematobium egg excretion rates showed a median reduction of 100% (interquartile range (IQR), 17% to 100%) and 65% (IQR, -133% to 100%) at 4-weeks and 6-weeks post-treatment, respectively, in the artesunate-pyronaridine group (n = 20) compared to 35% (IQR, -250% to 70%) and 65% (IQR, -65% to 79%) in the artemether-lumefantrine group (n = 18). Artesunate-amodiaquine (n = 2) and artefenomel-ferroquine combination (n = 3) were not able to reduce the rate of eggs excreted in this limited number of patients. In addition, cure rates were 56% and 37% at 4- and 6-weeks post-treatment, respectively, with artesunate-pyronaridine and no cases of cure were observed for the other antimalarial combinations. CONCLUSIONS: Antimalarial treatments with artesunate-pyronaridine and artemether-lumefantrine reduced the excretion of S. haematobium eggs, comforting the hypothesis that antimalarial drugs could play a role in the control of schistosomiasis. TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov, under the Identifier NCT04264130.

Female Genital Schistosomiasis (FGS) Associated with Well-Differentiated Squamous Cell Carcinoma of the Vulva: A Case Report.

INTRODUCTION: A case description of a rare incidence of female genital schistosomiasis related to vulva squamous cell carcinoma in a 76-year-old woman from the schistosomiasis-endemic region of Gombe State, Nigeria. Physicians should be aware of the high incidence rate of female genital schistosomiasis (FGS) in women and girls in schistosomiasis-endemic areas, which is often related to gynecological morbidity and the risk of HIV infection to avoid unnecessary interventions.

INTRODUCTION: Description d'une incidence rare de schistosomiase génitale féminine associée à un carcinome épidermique de la vulve chez une femme de 76 ans de la région endémique de la schistosomiase de l'État de Gombe, au Nigeria. Les médecins doivent être conscients du taux d'incidence élevé de la schistosomiase génitale féminine (SGF) chez les femmes et les filles dans les régions où la schistosomiase est endémique, ce qui est souvent lié à une morbidité gynécologique et au risque d'infection par le VIH, afin d'éviter des interventions inutiles. MOTS CLÉS: Schistosomiase génitale, Carcinome épidermoïde vulvaire, Femme.

Implication of serum Nitric oxide and IgE in urinary schistosomiasis: The case of Bamendjing, Cameroon.

BACKGROUND: Urinary schistosomiasis (US), also known as bilharziasis is a waterborne parasitic infection most common in rural areas of developing countries. The infection is associated with haematuria but little or nothing is known about its association with other urinary parameters, induction of Nitric Oxide (NO) and IgE production around the Bamendjing Dam an area highly suspected of Schistosoma haematobium infections. The study sought to address this problem for possible future interventions and control. MATERIALS AND METHODS: Urine samples were collected from 301 randomly selected participants and analysed for the presence of S. haematobium using the syringe filtration concentration method. Sera from patients infected with S. haematobium and also from some uninfected individuals were analysed for IgE and NO using ELISA and colorimetric methods respectively. FINDINGS: The results showed a prevalence of 16.9% (51/301). Sixty percent of the 49 patients with nitrite in their urine, were infected with urinary schistosomiasis (US) (30/49; p = 0.00). Meanwhile only 40% of the 15 patients with bilirubinuria were infected with US (6/15; p = 0.0241). The risk of patients with US having leucocytes and nitrites was high (OR of 1.3 and 1.7 respectively). Total IgE serum levels were significantly higher in patients with US (648.872 ± 223.142) compared to uninfected individuals (275.682 ± 181.674) (p = 0.00). Infected persons had heightened mean NO levels (2,583,617.647 ± 1,100,678.786) than non-infected participants (1,689,766.667 ± 1,163,084.729). Urinary Schistosomiasis in association with urinary parameters had a significant impact on mean IgE levels (F = 4.248, p = 0.022). Patients infected with Urinary Schistosomiasis alone had significantly higher mean total IgE levels than non-infected participants (p = 0.004). CONCLUSION: Apart from haematuria, this study has demonstrated that Urinary Schistosomiasis is prevalent among inhabitants around the Bamendjing Dam and results in an increase of other urine parameters such as leucocytes and nitrates and high levels of serum NO and total serum IgE in patients. These parameters are important in the screening of patients for treatment and control of urinary schistosomiasis.

Urinary schistosomiasis: a case of late presentation.

A man in his early 20s, originally from north-central Africa, presented with a high incidental serum creatinine level. A non-contrast CT scan was taken which was suggestive of urinary schistosomiasis. The diagnosis was confirmed on obtaining biopsies from the bladder. Due to bilateral hydronephrosis, an attempt at bilateral renal decompression was made. This failed to improve renal function. He eventually underwent a right nephrectomy. He is in end-stage renal failure, undergoing long-term dialysis, and has been placed on the waiting list for renal transplant.

Determinants of Urogenital Schistosomiasis Among Pregnant Women and its Association With Pregnancy Outcomes, Neonatal Deaths, and Child Growth.

BACKGROUND: Schistosoma haematobium is a parasitic helminth that causes urogenital pathology. The impact of urogenital schistosomiasis during pregnancy on birth outcomes and child growth is poorly understood. METHODS: Risk factors for urogenital schistosomiasis were characterized among 4437 pregnant women enrolled in a cluster-randomized community-based trial in rural Zimbabwe. Infection was defined via urine microscopy (≥1 S. haematobium egg) and urinalysis (hematuria). Associations between infection and pregnancy outcomes were assessed in case-control analyses using conditional logistic regression. The association of maternal infection with birthweight and length-for-age Z scores (LAZ) at 1 and 18 months of age were assessed using generalized estimating equations. RESULTS: Urogenital schistosomiasis (egg positive and/or hematuria positive) was detected in 26.8% of pregnant women. Risk factors significantly associated with infection were maternal age, education, marital status, and religion; household drinking water source and latrine; study region; and season. Urogenital schistosomiasis was not significantly associated with adverse pregnancy outcomes (miscarriage, stillbirth, preterm, and small-for-gestational age), birthweight, neonatal death, or LAZ. CONCLUSIONS: Including pregnant women in antihelminthic treatment programs would benefit a large number of women in rural Zimbabwe. However, clearance of the low-intensity infections that predominate in this context is unlikely to have additive benefits for pregnancy outcomes or child growth. CLINICAL TRIALS REGISTRATION: NCT01824940.

A 26-Year-old Woman With Dysuria and Hematuria.

In this case, we present imaging findings characteristic of chronic genitourinary schistosomiasis. Schistosoma haematobium, a blood fluke endemic to Africa and the Middle East, is a prominent cause of hematuria and bladder cancer in regions lacking adequate water sanitation. Luminal calcifications of the genitourinary tract, that is, of the bladder and/or ureters, from deposition of fluke eggs are a classic sign of chronic S. haematobium infection and should raise suspicion for the disease even when urine or serological tests are negative. It is important to recognize these findings on CT or, in resource-limited settings, plain film to allow for prompt, effective treatment.

Role of a schistosoma haematobium specific microRNA as a predictive and prognostic tool for bilharzial bladder cancer in Egypt.

Urinary bladder cancer is a common malignancy in Egypt, thus reliable methodologies are required for screening and early detection. In this study, we analyzed the gene expression of a Schistosoma hematobium specific microRNA "Sha-miR-71a" and mitogen-associated protein kinase-3 (MAPK-3) in the urine samples of 50 bladder cancer patients and 50 patients with benign bilharzial cystitis. Fifty control subjects were also tested. Indirect hemagglutination test (IHA) diagnosed 70% of studied cancer cases as bilharzial associated bladder cancer (BBC), while histopathological examination detected only 18%. Urinary Sha-miR-71a & MAPK-3 revealed enhanced expression in BBC (p-value = 0.001) compared to non-bilharzial bladder cancer (NBBC) cases. Patients with chronic bilharzial cystitis exhibited a significant increase in gene expression compared to those with acute infection (p-value = 0.001). Sha-miR-71a and MAPK-3 showed good sensitivity and specificity in the diagnosis of BBC when analyzed by the receiver operating characteristic (ROC) curve. They were also prognostic regarding malignancy grade. Both biomarkers showed a positive correlation. Our results revealed that IHA is a reliable test in the diagnosis of bilharziasis associated with bladder cancer, and that Sha-miR-71a and MAPK-3 provide non-invasive specific biomarkers to diagnose BBC, as well as a potential role in testing bilharzial patients for risk to develop cancer.

Urinary schistosomiasis and the associated bladder cancer: update.

BACKGROUND: Urinary schistosomiasis and its severe complications, mainly bladder cancer, are scarce in non-endemic areas. The deficiency in knowledge and clinical experience of schistosomiasis may lead to inadequate management. Highlighting these topics may be of value, especially with the increased immigration from endemic low-/middle-income countries (LMIC) to non-endemic high-income countries (HIC). Schistosomiasis is a parasitic infection endemic in many low- and middle-income countries. It can affect various systems but is best known for its effect on the urinary system. MAIN BODY: PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched for urinary schistosomiasis and its related bladder cancer published from 1980 till 2020. Schistosoma haematobium (SH) infecting the urinary bladder was considered by the IARC as group 1 definitive biological carcinogenic agent. Several carcinogenic pathways have been postulated but the exact mechanism(s) are not defined yet. A more thorough understanding of the parasite life cycle was explored to help eradicate the infection especially for the immigrants from endemic areas. This may prevent or slow down the process of carcinogenesis that leads to Schistosoma-associated bladder cancer (SA-BC), which is usually, but not conclusively, squamous cell carcinoma. Treatment of SA-BC generally follows the same guidelines as urothelial Schistosoma-non-associated bladder cancer (SNA-BC) management; however, prospective trials to confirm and refine the treatment approach for SA-BC have been relatively limited. CONCLUSION: The available data showed that despite some etiologic and carcinogenic differences, the oncologic outcomes are generally comparable for SA-BC and NSA-BC when adjusting for stage, risk status, and comorbidities.