https://orcid.org/0000-0002-0577-7404
Figures
Abstract
Background
Mozambique is one of the countries with the highest prevalence of schistosomiasis, although there is little data on the prevalence of disease and associated morbidity in the adult population. This study aimed to describe and characterize the morbidity associated with schistosomiasis in the adult population of Chókwè district and to explore the use of anamnestic questionnaires and urine dipsticks, as well as point-of-care ultrasound for urinary related findings, to better characterize disease prevalence and morbidity.
Methodology
Between April and October 2018, we conducted a cross-sectional study embedded within the Chókwè Health Research and Training Centre. Data were collected on sociodemographic variables, signs and symptoms for schistosomiasis and water related activities. Infection status was determined by urine filtration, Kato-Katz thick smear and DNA detection. Point-of care urinary tract ultrasonography was performed to assess structural morbidity associated with Schistosoma haematobium infection. Multivariate logistic regression was used to search for associations between risk factors, signs and symptoms, infection status and ultrasound abnormalities.
Principal findings
Our study included 1033 participants with a median age of 34 years old. The prevalence of Schistosoma haematobium, Schistosoma mansoni and ultrasound detected urinary tract abnormalities were 11.3% (95% CI 9.5%-13.4%), 5.7% (95% CI 4.3%-7.5%) and 37.9% (95% CI 34.8%-41.2%), respectively. Of the 37.9% with urinary tract abnormalities, 14.5% were positive for Schistosoma haematobium. Reported hematuria in the last month (p = 0.004, aOR 4.385) and blood in the urine dipstick (p = 0.004, aOR 3.958) were markers of Schistosoma haematobium infection. Reporting lower abdominal pain (p = 0.017, aOR 1.599) was associated with ultrasound abnormalities.
Conclusion
Using microscopy and DNA analysis for both Schistosoma haematobium and Schistosoma mansoni in conjunction with urinary ultrasound abnormalities gives us several insights into correlations between disease prevalence (microscopic and anatomical) and demographic details in a high-risk population.
Author summary
Schistosomiasis is one of the most common parasitic diseases in the world, mainly affecting people living in sub-Saharan Africa. Mozambique is one of the countries with the highest prevalence of the disease. Chronic urinary schistosomiasis in the adult population can lead to hematuria, anemia, urinary tract lesions and eventually death from renal failure and bladder cancer. The characteristics of the chronic form of disease in the adult population of Mozambique is unknown. A cross-sectional, community-based study was conducted to assess current morbidity and the risk factors for schistosomiasis among the adult population of Chókwè district, Mozambique. The prevalence of urinary schistosomiasis was 11.3%, intestinal schistosomiasis was 5.7% and urinary tract ultrasound abnormalities were 37.9%. Of the 37.9% with ultrasound abnormalities, 14.5% were positive for Schistosoma haematobium. In this study, reporting hematuria in the last month and blood in the urine were found to be diagnostic markers of urinary schistosomiasis, and reporting lower abdominal pain was associated with ultrasound abnormalities. The high prevalence of anatomical urinary tract ultrasound abnormalities suggests that the disease has an important impact on the long-term health of the adult population.
Citation: Serra JT, Silva C, Sidat M, Belo S, Ferreira P, Ferracini N, et al. (2024) Morbidity associated with schistosomiasis in adult population of Chókwè district, Mozambique. PLoS Negl Trop Dis 18(12): e0012738. https://doi.org/10.1371/journal.pntd.0012738
Editor: Josefina Zakzuk, University of Cartagena, COLOMBIA
Received: July 15, 2024; Accepted: November 28, 2024; Published: December 16, 2024
Copyright: © 2024 Serra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The data that support the findings of this study are publicly available from Zenodo with the identifier doi.org/10.5281/zenodo.12724648.
Funding: This work was funded by the "Joint WHO-AFRO/TDR/EDCTP Small Grants Scheme for implementation research on infectious diseases of poverty 2017”, whose responsible investigator was RT. Additionally, it received financial support from “Associação para Desenvolvimento da Medicina Tropical”, whose responsible investigator was JTS and from Fundação para a Ciência e a Tecnologia for funds to GHTM - UIDP/04413/2020 and LA-REAL – LA/P/0117/2020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Schistosomiasis, also known as Bilharzia, is an infectious disease classified as one of the 20 Neglected Tropical Diseases (NTDs), and remains a public health problem in several parts of the world, particularly in Africa, where 91% of infected people live [1]. Of the approximately 21 known species of Schistosoma, only 6 are pathogenic to humans, namely S. haematobium, S. mansoni, S. japonicum, S. mekongi, S. intercalatum and S. guineensis [2,3]. The immunology of schistosomiasis shows that the eggs, rather than the adult worms, are responsible for the pathological effects of infection [4]. The majority of clinical disease manifestations occur at body sites of increased egg accumulation, such as the bladder wall and ureters in case of S. haematobium infection and the liver, portal system and intestine for S. mansoni [5,6]. The classic sign of urinary schistosomiasis is the presence of blood in the urine. In advanced cases, kidney damage and fibrosis of the bladder and ureters can occur [7]. Bladder cancer is a reported complication in later stages of S. haematobium infection and the parasite is therefore classified as carcinogen [8,9]. Intestinal schistosomiasis can cause abdominal pain, diarrhea and presence of blood in the stools [7]. The diagnostic algorithm for schistosomiasis includes important anamnestic questions, specific clinical signs and supporting laboratory investigation [10].
Mozambique is one of the countries with the highest prevalence of schistosomiasis [11]. Several studies have reported a wide geographical variation in the prevalence of schistosomiasis in the country, depending on the location and population studied [12–27]. The most recent nationwide study estimated a global prevalence of 53.5% for geohelminths, 47% for S. haematobium and 1% for S. mansoni among individuals aged 7–22 years old [28]. The morbidity and mortality associated with schistosomiasis are grossly underestimated in most countries and long-term morbidity mainly affects adults resulting in chronic diarrhea, malabsorption, renal failure and bladder cancer [29–31]. The economic and social impact of the disease results in reduced ability to work and a reduction in available family income [32]. In an attempt to quantify the clinical morbidity associated with schistosomiasis in sub-Saharan Africa, hematuria associated with S. haematobium infection was estimated to occur in 70 million individuals and dysuria in 32 million. Vesical wall lesions and hydronephrosis were estimated to affect 106 and 18.9 million people, respectively. S. mansoni infection caused diarrhea in 780000 people, blood in the stool in 4.4 million and hepatomegaly in 8.5 million. Mortality due to end-stage renal disease and upper gastrointestinal bleeding accounted for 150000 and 130000 deaths per year, respectively [33,34].
Mozambique began mass treatment of school-aged children with Praziquantel in 2010. By 2011, approximately 32.8% of the country had been covered [35]. Although treatment of adults in hyperendemic areas (>50%) and at-risk groups in areas with prevalence below 50% was planned, it was not consistently achieved due to material and human resource difficulties, as well as a lack of data [35]. Detection of NTD-related morbidity is a major challenge, given the limited availability of laboratory and other diagnostic facilities in most health facilities throughout the country, and also due to the lack of qualified staff to diagnose complications. Reducing the morbidity associated with schistosomiasis by 2020 was one of the goals of the Mozambican Integrated National Plan for the Control of Neglected Tropical Diseases 2013–2017 [35].
Ultrasound has demonstrated significant diagnostic capabilities in assessing morbidity due to various infectious diseases in tropical settings [36–39]. The World Health Organization (WHO) has recognized its good safety, flexibility and cost-effectiveness in assisting in the diagnosis of morbidity. In the specific case of urinary schistosomiasis, ultrasound has been shown to be a good alternative to other invasive procedures such as cystoscopy [40]. The use of bedside ultrasound by clinicians to facilitate urgent assessment or to support invasive procedures, has become increasingly popular and it`s being incorporated into medical training programs worldwide [36]. In areas highly endemic for S. haematobium infection, urinary ultrasound findings such as hydronephrosis, hydroureter, bladder wall thickening, and bladder wall polyps and/or masses, have been considered a good proxy for schistosomiasis related morbidity [41].
An important gap in the prevalence of disease associated morbidity for schistosomiasis in the adult population of Mozambique remains. The aim of this study was to describe and characterize the morbidity associated with schistosomiasis in the adult population of Chókwè district and to explore the correlation with anamnestic questionnaire results and microbiologic findings. Ultrasound was used to assess anatomical abnormalities and results of these findings are mentioned briefly in this paper, but will be more completely described in an upcoming publication.
Methods
Ethical considerations
Administrative approval was obtained from the Gaza Provincial Health Directorate and the protocol was submitted to the Institutional Bioethics Committee of the National Institute of Health and the Mozambican National Bioethics Committee for Health (83/CNBS/2017). Final administrative approval was deferred by the Minister of Health of Mozambique. The Chókwè Consultative Committee was consulted and the District Health, Women and Social Action Service, the District Government and the Municipal Council of the town of Chókwè were informed as part an ongoing collaboration. The conditions for the transfer of biological material between the Chókwè Health Research and Training Center (CITSC) and the Institute of Hygiene and Tropical Medicine from NOVA University were established under a biological material transfer agreement between the two institutions.
Depending on their age and spoken language (Portuguese or Changana), each individual was given an informed consent form. In case of acceptance, individuals over 18 years old signed a written consent form or, in case of illiteracy, printed their fingerprint, in which case the signature of a witness outside the research team was required. In the case of minors (15 to 17 years old), in addition to the fingerprint or written consent of the minor, the consent of the legal guardian was required, following a procedure similar to that described above in the case of individuals over 18 years old. All consent forms were completed in duplicate, with one copy kept by the participant and the other by the research team.
A preparatory meeting was held in each of the units prior to field activities in order to present and explain the study. At the end of the study, medical treatment was provided to all participants with schistosomiasis or other diagnosed intestinal parasitic infection. If any ultrasound abnormalities were detected that required additional treatment, participants were referred to the nearest health facility for further treatment.
Study area and population
Covering an area of 2466 km2, Chókwè is a small and densely populated district (88 inhabitants/Km2) in the south of Gaza province, Mozambique (Fig 1). In the 1950s, the construction of a dam allowed the development of a large irrigation area consisting of several canals and ditches. This ecological change allowed for the spread of schistosomiasis and other tropical diseases [42,43].
The study took place in Chókwè district, Gaza province, south of Mozambique. Map created using ArcGIS Pro 3.3.0. Base layer map provided by GADM—University of California-Davis, Mapcruzin, Stanford University, available from: https://icedrive.net/s/50XyM9uso5.
The Chókwè Health Research and Training Center is a research center of the National Institute of Health of Mozambique established in 2007. This center has been implementing and managing a continuous demographic surveillance system (HDSS) since 2010 and has been part of the “International Network for Demographic Evaluation of the Population and Their Health” (INDEPTH) since 2014 [44]. The HDSS covers a geographical area of about 600 km2 and includes 14 administrative units, of which 7 are classified as neighborhoods of the town of Chókwè and 7 as villages in the district. In 2018, 19877 aggregates were active in the HDSS database, representing about 100000 of the 183000 inhabitants of Chókwè district. All individuals registered in the HDSS are identified with a unique, lifelong and non-transferable code that allows the individual to be tracked in the community. In Chókwè district, the prevalence of S. haematobium infection in school-aged children is estimated to be 35%, but no specific data is available on the prevalence of S. mansoni infection in the district (personal communication).
Study design and sampling
We conducted a cross-sectional study of individuals aged 15 years or older (WHO defines school-age as 5–15 for schistosomiasis control strategies), living in households registered in the HDSS database in 2018. In that year, the HDSS registered 19578 households with at least one member aged 14 years or older. A two-stage cluster sampling procedure was used to calculate the sample. For this purpose, the household was considered as the primary sampling unit and the smallest administrative units of the HDSS as the secondary sampling unit. The number of clusters required was determined on the basis of the methodology recommended by the WHO in the Extended Program on Immunization [45]. The selection of 30 clusters was therefore recommended, with the aim of enrolling 30 individuals per cluster (30x30). Considering the smallest administrative units of the HDSS (n = 131) as the secondary sampling unit, but taking into account the variation in the number of households that make up each unit, the probability proportional to population size method was used to standardize the probability of selection for each of the clusters. After systematically selecting 30 HDSS units, the second step was to select 30 individuals in each of the 30 clusters. Therefore, using the household as the primary sampling unit, it was necessary to calculate the number of households required to include at least 30 individuals per cluster. With an average of 2 persons aged 15 or over per household, 13 households would be required to obtain at least 30 persons per cluster. A refusal rate of 20% was also included in the calculation, in line with experience from previous studies conducted by CITSC. The final calculation resulted in 19 households per cluster, which were randomly selected from the HDSS database, resulting in a total of 570 households selected to participate in the study.
For each of the clusters, a list of selected households was generated, containing the name and date of birth of the members as recorded in the HDSS database. However, given the high mobility of the population and the likelihood of outdated data, if none of the members of a household could be found after two attempts, or if their dwelling could not be located, the household was replaced by the nearest one whose members were present. All participants who reported living in the house at the time of the survey were included, regardless of whether they were on the researcher`s list or how long they had lived in the household.
The inclusion and exclusion criteria for the study were applied by the research team members in the field. Inclusion criteria included: age 15 years or older at the time of recruitment; living in the selected household at the time of recruitment; ability to understand and consent. Exclusion criteria were as follows: known or ultrasound documented pregnancy (pregnancy is known to increase rates of hydronephrosis independent of pathology) at the time of recruitment; history of abdominal trauma requiring medical attention in the previous 6 months; history of kidney or bladder surgery, documented by the presence of an abdominal or back scar not attributable to another cause reported by the participant; individuals not located after at least two location attempts; individuals not providing a biological sample.
Individual and household data
Before starting the work in the selected clusters and aggregates, a pilot study was conducted to test the procedures and adjust the working methodology. The fieldwork was carried out between April and October 2018. The individual questionnaire (S1 Appendix) was developed on the basis of previously used questionnaires, which were further developed to allow the assessment of demographic information, signs, symptoms and water related activities [46–48]. It was administered by members of the research team with the exception of the main researcher. This was not only due to the frequent need for fluency in Changana when interacting with the participant, but also to allow the main researcher to be unaware of the presence of signs and symptoms suggestive of disease when performing the ultrasound. The questionnaire was completed electronically using a tablet. Completion of the individual questionnaire was mandatory for all participants, who were identified only by the individual code assigned in the context of this study. A housing conditions questionnaire (S2 Appendix) based on information previously recorded by the HDSS surveillance system was completed for each of the study households. All participating households were required to complete a housing conditions questionnaire.
Sample collection and analysis
Urine was collected between 10:00 and 14:00 although it was occasionally necessary to collect outside these hours. Fecal samples were preferentially collected early in the morning. Samples were then placed in a thermal suitcase with cooling devices, transported to the CITSC laboratory and analyzed using standardized quality-controlled techniques, preferably within 24 hours of collection. Urine samples were examined microscopically for S. haematobium and were also tested for blood, leukocytes, proteins and nitrites [49]. Kato-Katz (KK) thick smears were examined microscopically for S. mansoni, soil-transmitted helminths and other parasites [50].
For molecular analysis, all urine and fecal samples were centrifuged, the sediment was stored at –20°C and transferred to long-term –80°C storage at the Institute of Hygiene and Tropical Medicine of the NOVA University Laboratory. Genomic DNA extraction was performed using the Speed Tools Tissue DNA kit (Biotools B&M Labs, Madrid, Spain) according to the manufacture’s protocol. For the PCR analysis, specific primers for S. haematobium and S. mansoni, were sequenced (Stab Vida, Caparica, Portugal) [51,52].
Point-of-care ultrasounds
The full details of the ultrasound protocol and image analysis will be detailed in a separate paper. Briefly, all study participants were invited to undergo an abdominal ultrasound using a portable ultrasound system. Ultrasound was not a mandatory part of the study; absence of ultrasound results did not result in the exclusion of a participant from other aspects of study analysis. Ultrasound examinations followed a predetermined protocol which was developed based on the WHO recommendations for the assessment of structural changes associated with S. haematobium infection, incorporating modifications suggested in more recent literature (S3 Appendix) [53–55].
Statistical analysis
Participants were considered positive for schistosomiasis infection if at least one of the diagnostic methods (parasitological or molecular test) gave a positive result. Urine dipstick results were classified as negative and positive. Participants with at least one positive item on the ultrasound protocol were classified as having a urinary tract abnormality.
The statistical methods used included descriptive statistics, bivariate analysis using odds ratio and multivariate logistic regression modelling. Descriptive statistics were used to measure relative frequencies and percentages of the variables. Bivariate analysis was performed to identify the factors associated with S. haematobium infection, S. mansoni infection and ultrasound abnormalities to be included in the multivariate logistic regression for risk factor analysis. Chi-squared tests or Fisher’s exact test, when the conditions for applicability were not met, were used to determine the association between variables. Variables with significance at values 0.05 in the univariate test and/or with biological plausibility were selected for multivariate logistic analysis, to identify the risk factors for S. hematobium, S. mansoni and ultrasound abnormalities. Results were reported as crude odds ratios (cOR) with 95% confidence intervals (CI) and adjusted odds ratios (aORs) with 95% confidence intervals, together with the test for significance. Data analysis was performed using IBM SPSS (version 29.0) and p-values less than 0.05 were considered significant.
Results
Study participation and compliance
The final study sample consisted in 1033 individuals aged 15 years and over (Fig 2).
Participants were recruited between April and October 2018.
Sociodemographic and household`s characteristics
Sociodemographic characteristics are summarized in Table 1. Most participants were female (71.7%) and ranged in age from a minimum of 15 years to a maximum of 98 years. The median age was 34 (IQR 32) years.
Table 2 shows the characteristics of the households. Most of them (61.1%) were located in the semi-urban area of Chókwè town and the rest (38.9%) in the rural area of the district. The average number of persons living in the same house was 6.4, with a minimum of 1 and a maximum of 20. The average number of persons under the age of 15 living in the same house was 2.6, ranging from 0 to 13.
Health-related characteristics
The most commonly reported symptom was fever (39.3%), followed by lower abdominal pain (35.1%) and dysuria (30.9%). The proportion of people positive for S. haematobium infection reporting hematuria in the last month was 45.5% and for those with a documented ultrasound abnormality was 64.1% (Table 3).
Infection, urine dipstick and ultrasound data
The prevalence of infection by egg and/or DNA detection was 11.3% (95% CI 9.5%-13.4%) for S. haematobium and 5.7% (95% CI 4.3%-7.5%) for S. mansoni (Table 4). There were 3 cases of co-infection with both species. Infection intensity for S. haematobium infection was light (<50eggs/10mL) in 34/38 (89.5%) and heavy (≥50 eggs/10mL) in 4/38 (10.5%) of cases. For intestinal schistosomiasis, the only samples positive for S. mansoni eggs had a light infection intensity (<100epg). The proportion of people infected with S. haematobium was higher in rural areas (16.9% vs 7.8%), but the results for S. mansoni infection were slightly higher in semi-urban areas (5.4% vs 6.2%). Parasitological results for other intestinal parasites are presented in S4 Appendix.
Blood in the urine was the most common urine dipstick finding (19%), followed by proteinuria in 14.2% of cases. With regard to blood in the urine, 5.3% (39/741) of women were excluded because they were menstruating or had menstruated in the previous 48 hours. Of those reporting blood in the urine, 24.6% were infected with S. haematobium and 44.9% had an ultrasound abnormality (Table 5).
Of the 912 ultrasound scans performed, 37.9% (346/912) were classified as abnormal, of which 14.5% (50/346) were confirmed positive for S. haematobium. An inferior urinary tract abnormality was found in 11.8% (108/912) and an upper urinary tract abnormality in 29.7% (271/912). More specific details of ultrasound abnormalities will be detailed in a future publication. Assuming that a urinary tract ultrasound abnormality is an indirect measure of chronic schistosomiasis in the present epidemiological context, the overall prevalence of structural morbidity associated with schistosomiasis is 37.9% (95% CI 34.8%-41.2%).
Water activities
Regarding the usual water activities (Table 6), 43.7% reported some contact with water from rivers, streams or lakes. The most common water activity was using water from rivers, streams or lakes for agricultural activities (29.6%), followed by crossing rivers, streams or lakes (28.7%). More than 90% of participants reported using soap for washing (99.3%), doing laundry (98.1%) and washing dishes (95.5%), but less than 50% used soap for hand washing (46.9%).
Association of Schistosoma infection with risk factors and morbidity parameters
All variables were analyzed for bivariate association with S. haematobium infection, S. mansoni infection and ultrasound abnormalities (S5, S6 and S7 Appendices), but most of them dropped out when included in a multivariate model. Age (p = 0.003), time of residency in Chókwè (p<0.001), occupation (p = 0.009) and the number of people living in the same house less then 15 years old (p = 0.004) were the sociodemographic characteristics associated with S. haematobium infection (Table 7). Reporting hematuria anytime in life (p = 0.004) and hematuria in the last month (p<0.001), were the only symptoms associated with infection. Of all the water activities examined, a positive association was found with seven of them (Table 7). After multivariate analysis, the only four variables with statistical significance were: age (p = 0.011, aOR = 0.977, 95% CI 0.959–0.995), students (p = 0.025, aOR = 0.389, 95% CI 0.170–0.890), reporting hematuria in the last month (p = 0.002, aOR = 4.267, 95% CI 1.718–10.596) and blood in urine dipstick (p<0.001, aOR 3.193, 95% CI 1.834–5.560).
As shown in Table 8, females (p = 0.035) were more likely to be infected with S. mansoni. Participants who reported doing laundry (p = 0.004) and using water from rivers, streams or lakes for other activities (p<0.001), were more likely to be infected with S. mansoni, but only this last activity retained significancy in the multivariate analysis (p = 0.017, aOR 2.452, 95% CI 1.172–5.130).
Being born in Chókwè (p = 0.026), reporting hematuria (p = 0.001), dysuria (p<0.001), lower abdominal pain (p = 0.001), nitrites (p = 0.003), blood in urine dipstick (p = 0.034) and S. haematobium infection (p = 0.005) were all associated with participants having a urinary tract ultrasound abnormality. After multivariate analysis (Table 9), individuals born in Chókwè district (p = 0.007, aOR 0.608, 95% CI 0.423–0.875) and reporting lower abdominal pain in the last month (p = 0.017, aOR 1.599, 95% CI 1.089–2.349) had significantly higher odds of having an ultrasound abnormality.
Discussion
The objectives of this study were to describe and characterize the morbidity associated with schistosomiasis in the adult population of Chókwè district and to explore the use of anamnestic questionnaires and molecular results to highlight positive correlations. Multivariate analysis showed that younger people, students, people reporting hematuria in the last month or with blood in the urine dipstick had an increased risk of urinary schistosomiasis. Urinary tract ultrasound abnormalities were found in 37.9% of participants, of which 14.5% were positive for S. haematobium. Individuals reporting lower abdominal pain in the last month had higher chances of having an ultrasound abnormality.
Infection prevalence in Chókwè district
Our results confirmed the presence of both S. haematobium (11.3%, 95% CI 9.5%-13.4%) and S. mansoni (5.7%, 95% CI 4.3%-7.5%) infection among adults registered in the Chókwè HDSS. The only previous data available on the prevalence of schistosomiasis in this area of Mozambique dates back to the 1950s, reporting a prevalence of 37.7% for S. haematobium and 0.4% for S. mansoni in indigenous adults, 2.86% for S. haematobium in the European population, and 68% for S. haematobium and 2% for S. mansoni in school-aged children [12,15,16]. A recent study in the Manhiça area, reported a prevalence of S. haematobium and S. mansoni in adults of 7.1% and 3.1%, respectively [27]. However, the Ministry of Health reported a S. haematobium prevalence of 35% among Chókwè school-aged children in 2005–2007. Although there are no specific data on S. mansoni in Chókwè district, the reported prevalence among school-aged children for Gaza province is 0.8% [28]. The discrepancy between the previous S. haematobium data and the current actual findings in the adult population (37.7% in 1952 versus 11.3% in 2018) may be due to several reasons.
Firstly, water, sanitation and hygiene conditions, one of the cornerstones of schistosomiasis control, has been steadily improving in Mozambique, contributing to a reduction in schistosomiasis prevalence [56,57]. In our study, 89.2% of people had piped water, most of them inside the house or in the backyard, and 95.3% had a sanitation facility, the majority of which was a basic latrine (54.8%), which is a major improvement compared to the housing conditions of the local population is the 1950s. Secondly, two mass chemotherapy campaigns took place in 2014 and 2016, covering 91% and 90% of school-aged children in Chókwè, respectively (personal communication). These campaigns likely reduced prevalence among school-aged children, thereby reducing transmission rates and decreasing prevalence in the adult population.
Diagnostic challenges in low prevalence areas
Although parasitological detection of Schistosoma remains the cornerstone of schistosomiasis diagnosis, a sharp decline in sensitivity in low endemic areas affect disease assessment [58,59]. The main method used to diagnose urinary schistosomiasis is to filter and concentrate S. haematobium eggs from urine, followed by microscopic examination. Eggs are generally easy to identify, but these tests tend to have low sensitivity in the adult population, mainly due to reduced egg excretion with chronicity of the disease [60]. The Kato-Katz thick stool smear method, which also relies on microscopy, is still widely used and is the WHO recommended standard for the diagnosis of intestinal schistosomiasis. When the host has a high number of worms, the sensitivity of KK is high because of the large number of eggs excreted, but as with urine filtration for S. haematobium diagnosis, the accuracy of the test decreases in individuals with mild infections and in regions of low disease prevalence [61,62]. In addition, schistosome egg excretion fluctuates daily, leading to high variability in KK test results due to overdispersal of egg production, especially in cases of mild infections. The exact level of disease impact within a community may be significantly underestimated by the KK method. Therefore, because of their simplicity and cost-effectiveness, KK and urine egg detection techniques are particularly well suited to settings with high schistosome transmission levels, but lack the necessary sensitivity in areas of low endemicity. Our study found a prevalence of S. haematobium and S. mansoni of 3.7% and 0.2% by parasitological testing compared with 10% and 4.9% by DNA detection, respectively (Table 4). Our data highlights the need to search for new methods of evaluation that can answer to the current challenges of schistosomiasis diagnosis and control in populations with lower parasite burden [63,64].
Ultrasound abnormalities and chronic schistosomiasis
To our knowledge, this work is the first to systematically address the issue of structural abnormalities associated with schistosomiasis in the adult population of Mozambique. Studies in other endemic regions show that the prevalence of ultrasound findings in patients with schistosomiasis can be quite variable [41,65–67]. We found that 37.9% (95% CI 34.8%-41.2%) of adult individuals living in Chókwè HDSS had a structural urinary tract abnormality detected by ultrasound. S. haematobium detected by egg and/or molecular analysis was not a consistent predictor of ultrasound abnormality (p = 0.279, aOR 1.364 95% CI 0.778–2.392). Further analysis of ultrasound approach and findings will be detailed in an upcoming publication.
Contact with water from rivers, streams or lakes (p = 0.212, aOR 0.796 95% CI 0.556–1.139) and a history of schistosomiasis (p = 0.381, aOR 0.789 95% CI 0.465–1.340) were not found to be a risk factor for ultrasound abnormalities that might otherwise indicate a schistosomiasis related lesion. Serological diagnosis of schistosomiasis may have been helpful in our case, although previous studies note that serology alone is not a good predictor of ultrasound abnormalities, but it may be useful in combination with other findings such as blood in urine dipstick [68]. Our findings reinforce the value of ultrasound as an adjunct to diagnosis and screening in S. haematobium endemic areas. Ultrasound provides immediate data on disease-related changes associated with urinary schistosomiasis, but also has a remarkable correlation with other more invasive investigations such as cystoscopy [40,69]. A POCUS ultrasound approach should be considered as an important tool for routine screening of urinary tract lesions in schistosomiasis endemic areas, particularly in resource-limited settings where traditional diagnostic tools are less accessible.
Schistosomiasis screening with anamnestic questionnaires
Screening questionnaires have been found to be an extremely useful method, as a first step in identifying communities with a high prevalence of schistosomiasis, and their use has been recommended by WHO in the Manual for Schistosomiasis since 1995 [70]. Over the years, the use of screening questionnaires has been tested and validated in several countries, confirming the good performance of this indirect method in identifying communities at high risk of S. haematobium infection [47,48]. However, in only one of these studies was the population studied in adulthood [71]. In a review of the use of urinary schistosomiasis screening questionnaires in sub-Saharan Africa, a total of 133880 children were screened using this method. The positive predictive value ranged from 31% to 92% and the negative predictive value from 75% to 100%, confirming the good performance of the questionnaires in screening for urinary schistosomiasis at the community level. On the other hand, their use in the individual screening for infection showed that reporting hematuria and a history of schistosomiasis were good indicators of infection. However, the use of individual questionnaires does not identify a high percentage of mild infections, which can be a problem in controlling morbidity [47]. With the introduction of mass chemotherapy as a control strategy, the high prevalence and morbidity associated with the disease decreased significantly [72]. We found that younger individuals (p = 0.011, aOR = 0.977, 95% CI 0.959–0.995) have a higher risk of being infected with S. haematobium. This finding seems logical, since younger individuals usually spend more time having recreational activities in rivers and lakes, and so, are more exposed to disease transmission.
Our results also confirmed that reported hematuria in the last month is a marker of S. haematobium infection (p = 0.002, aOR = 4.267, 95% CI 1.718–10.596), but did not find an association with a history of schistosomiasis or with any of the other health characteristics. Several studies have demonstrated the good correlation between reported hematuria and a high prevalence of S. haematobium, but in our case this correlation remains even in an adult population with low disease prevalence [47,73,74].
Another possible importance of screening questionnaires, is their use in identifying structural urinary tract morbidity associated with schistosomiasis. We found that people reporting lower abdominal pain in the last month (p = 0.017, aOR 1.599 95% CI 1.089–2.349) had higher chances of having an ultrasound abnormality. There was no significant association between reported hematuria (p = 0.511, aOR 1.340 95% CI 0.559–3.214), medical history including previous schistosomiasis infection (p = 0.381, aOR 0.789 95% CI 0.465–1.340) or contact with water from rivers, streams or lakes (p = 0.212, aOR 0.796 95% CI 0.556–1.139) with ultrasound abnormalities. This means that questions used to identify infected individuals in screening questionaries are not effective for identifying people with possible schistosomiasis associated urinary structural morbidity without a positive diagnostic test. Nevertheless, it may be worth further exploring the role of questions about bladder or lower abdominal pain as markers for ultrasound abnormalities. Another risk factor for an ultrasound abnormality was being born in Chókwè district (p = 0.007, aOR 0.608 95% CI 0.423–0.875), implying a possible longer or more intense exposure to disease transmission, as Chókwè district is home to one of the largest irrigation schemes in Mozambique and therefore has favorable conditions for disease transmission.
Community screening questionnaires have also been analyzed for S. mansoni infection, with positive predictive values ranging from 20% to 88% and negative predictive values ranging from 32% to 95%. The presence of blood in the stool and bloody diarrhea were the best diagnostic markers of infection [47,48,75]. Furst et al discuss the use of screening questionnaires in low endemicity areas and suggested that they have low sensitivity and specificity in identifying individuals infected with S. mansoni and geohelminths [76]. Our study confirms previous findings, as no association was found between any symptoms and S. mansoni infection in a low endemicity area. The only risk factor found for intestinal schistosomiasis was the use of water from rivers, streams or lakes for other activities (p = 0.017, aOR 2.452 95% CI 1.172–5.130).
Urine dipsticks as a diagnostic marker
Like screening questionnaires, urine dipstick testing has been shown to be an effective, inexpensive and easy-to-use tool for identifying communities at high risk of infection [47,77]. However, their ability to detect infection is reduced in low prevalence areas, previously treated populations, or subgroups with mild infection. Urine dipsticks have a particularly low diagnostic accuracy for detecting ultra-light infections [78,79]. In our study, blood in urine is a marker of S. haematobium infection (p<0.001, aOR 3.193, 95% CI 1.834–5.560). In contrast, we found no association between blood in urine and ultrasound abnormalities (p = 0.348, aOR 1.237 95% 0.793–1.930). This could be partly explained by the type of the ultrasound abnormality, as in this analysis we do not distinguish between upper and lower urinary tract abnormalities, nor do we grade the severity of the lesions.
Limitations and strengths
As the main strength of this study is the fact that it was the first to systematically evaluate schistosomiasis associated urinary tract abnormalities in an adult population of a rural district in Mozambique. Furthermore, it assessed Schistosoma spp. infection status using a combination of parasitological and molecular methods, thereby increasing the sensitivity and specificity of laboratory diagnosis of schistosomiasis, particularly in an area of low to moderate disease endemicity. In this cross-sectional study, we have simultaneously assessed schistosomiasis health related issues such as symptoms and medical history, water activities, performed several diagnostic methods and evaluated urinary tract abnormalities. However, there are several limitations to our study. First, the exact etiology of ultrasound abnormalities cannot be determined. In a schistosomiasis endemic area such as Chókwè district, we assume that the urinary tract structural lesions documented by ultrasound are probably a consequence of Schistosoma spp. infection, although the cross-sectional nature of the study design and the lack of other supporting laboratory data such as serology for schistosomiasis infection, limit the causal inference for the nature of the ultrasound abnormalities. Indeed, other risk factors for bladder lesions, such as smoking habits, were not addressed in the present study. Also, the presence of other diseases such as HIV and tuberculosis was assessed by questionnaires only and may be underestimated due to recall bias and social desirability. At last, the prevalence of kidney stones in Mozambique, a possible cause for ureter dilatation, is unknown. Second, the prevalence of other non-communicable diseases, such as diabetes and hypertension, other possible causes of urinary tract symptoms and urine dipstick abnormalities in the population studied, was also not addressed.
Conclusions
The current study provides valuable insights into the morbidity associated with S. haematobium, characterizing for the first time the infection related urinary tract abnormalities in the adult population of Chókwè district and contributing to the understanding of the burden of the disease in Mozambique. Reported hematuria and blood in urine dipsticks are good infection markers, but do not appear to be important in urinary tract structural lesions identification.
Supporting information
S1 Appendix. Individual questionnaires in Portuguese and English.
https://doi.org/10.1371/journal.pntd.0012738.s001
(PDF)
S2 Appendix. Housing conditions questionnaires in Portuguese and English.
https://doi.org/10.1371/journal.pntd.0012738.s002
(PDF)
S3 Appendix. Ultrasound record sheet in Portuguese and English.
https://doi.org/10.1371/journal.pntd.0012738.s003
(PDF)
S4 Appendix. Laboratorial results for other intestinal parasites.
https://doi.org/10.1371/journal.pntd.0012738.s004
(PDF)
S5 Appendix. Association analysis for S. haematobium infection.
https://doi.org/10.1371/journal.pntd.0012738.s005
(PDF)
S6 Appendix. Association analysis for S. mansoni infection.
https://doi.org/10.1371/journal.pntd.0012738.s006
(PDF)
S7 Appendix. Association analysis for ultrasound abnormalities.
https://doi.org/10.1371/journal.pntd.0012738.s007
(PDF)
Acknowledgments
The authors would like to thank all the inhabitants in the catchment area of the Chókwè Health Demographic Surveillance System for their enthusiastic participation in the present study. We are also grateful for the assistance received from Chókwè local leaderships for their guidance related to household’s location and participants mobilization. We are indebted to the political and health authorities for their kind collaboration. Sincere thanks also go to the staff of the Chókwè Health Research and Training Center/Mozambique`s National Institute of Health for their assistance in the study field work implementation, in particular to the drivers and community engagement workers for their skillful work in the field, the laboratory technicians for their exceptional cooperation and to the research assistants (Mr. Jorge Paiva, Ms. Anatércia Mujovo and Ms. Emília Campira) for their invaluable support in data collection. We would also like to give our thanks to the World Health Organization for their kind support on donating the of OvoFec Kits and to Ms. Susana Nunes for the study location map design.
References
- 1.
World Health Organization. Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021–2030. Geneva: World Health Organization; 2020. [cited 2024 Jun 26]. Available from: https://www.who.int/publications/i/item/9789240010352
- 2. Webster BL, Southgate VR, Littlewood DT. A revision of the interrelationships of Schistosoma including the recently described Schistosoma guineensis. Int J Parasitol. 2006 Jul;36(8):947–55. Epub 2006 Apr 25. pmid:16730013.
- 3. Brant SV, Loker ES. Discovery-based studies of schistosome diversity stimulate new hypotheses about parasite biology. Trends Parasitol. 2013 Sep;29(9):449–59. Epub 2013 Jul 11. pmid:23849836.
- 4. Schwartz C, Fallon PG. Schistosoma "Eggs-Iting" the Host: Granuloma Formation and Egg Excretion. Front Immunol. 2018 Oct 29;9:2492. pmid:30459767.
- 5. Tamarozzi F, Fittipaldo VA, Orth HM, Richter J, Buonfrate D, Riccardi N, et al. Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature. PLoS Negl Trop Dis. 2021 Mar 25;15(3):e0009191. pmid:33764979.
- 6. Manciulli T, Marangoni D, Salas-Coronas J, Bocanegra C, Richter J, Gobbi F et al. Diagnosis and management of complicated urogenital schistosomiasis: a systematic review of the literature. Infection. 2023 Oct;51(5):1185–1221. Epub 2023 Jul 19. pmid:37466786.
- 7. Carbonell C, Rodríguez-Alonso B, López-Bernús A, Almeida H, Galindo-Pérez I, Velasco-Tirado V, Marcos M, Pardo-Lledías J, Belhassen-García M. Clinical Spectrum of Schistosomiasis: An Update. J Clin Med. 2021 Nov 25;10(23):5521. pmid:34884223.
- 8. World Health Organization. Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241. pmid:7715068.
- 9. Ishida K, Hsieh MH. Understanding Urogenital Schistosomiasis-Related Bladder Cancer: An Update. Front Med (Lausanne). 2018 Aug 10;5:223. pmid:30159314.
- 10. Gray DJ, Ross AG, Li YS, McManus DP. Diagnosis and management of schistosomiasis. BMJ. 2011 May 17;342:d2651. pmid:21586478.
- 11. Grau-Pujol B, Massangaie M, Cano J, Maroto C, Ndeve A, Saute F, et al. Frequency and distribution of neglected tropical diseases in Mozambique: a systematic review. Infect Dis Poverty. 2019 Dec 13;8(1):103. pmid:31836025.
- 12. Beuchat A. Estudo das helmintiases e bilharzioses no concelho de Gaza, Baixo-limpopo. Anais do Instituto de Higiene e Medicina Tropical. 1952 Dec;IX(4):1081–1085.
- 13. de Azevedo JF, Colaço A, Faro M. As bilharzioses humanas no Sul do Save (Moçambique). Anais do Instituto de Medicina Tropical. 1954 Mar;XI(1):5–120.
- 14. Alves W. Bilharziasis in Africa: A review. Cent Afr J Med. 1957 Apr;3(4):123–134. pmid:13461078
- 15. de Azevedo JF, Faro M, Morais T, Dias J. As bilharzioses humanas no território de Manica e Sofala e na área da barragem do Limpopo (Moçambique). Anais do Instituto de Medicina Tropical. 1957 Mar-Jun;14(1–2):5–103.
- 16. Morais T. Sobre um inquérito parasitológico aos colonos europeus estabelecidos no esquema de irrigação do vale do Rio Limpopo. In: Proceedings of the Sixth International Congress on Tropical Medicine and Malaria; 1958 Sept 5–13; Lisbon. Lisbon: Anais do Instituto de Medicina Tropical. 2:183–193.
- 17. Torres FO. Hidronefroses: sua frequência e causas em Moçambique. Anais do Instituto de Medicina Tropical. 1965 Jan-Dec;22(1–4):163–168.
- 18. Ruas A, Luís F. Tratamento de 1059 casos de Bilharzíase vesical e intestinal pelo CIBA-32644-BA. Revista dos Estudos Gerais Universitários de Moçambique. 1966;III(III):137–151.
- 19. Torres FO. Cancer of the bladder in the Portuguese East Africans: an evaluation of lymphoid tissue depletion in Portuguese East Africans. Revista de Ciências Médicas da Universidade de Lourenço Marques. 1971;4(1):83–100.
- 20. Santos NT. Parasitoses intestinais: Prevalência na população infantil, banto, suburbana da cidade de Lourenço Marques. Revista de Ciências Médicas da Universidade de Lourenço Marques. 1973;6(2):243–264.
- 21. Ebert W. Untersuchungen zur Häufigkeit und Bedeutung der Bilharziose in der Volksrepublik Moçambique [Incidence and significance of bilharziasis in the Republic of Mozambique]. Z Urol Nephrol. 1987 Nov;80(11):625–8. German. pmid:3125701.
- 22. Traquinho GA, Júlio A, Thompson R. Bilharziose vesical em Boane, Província de Maputo. Revista Médica de Moçambique. 1994 Dec:5(4):20–23. Augusto G, Vaz R. Parasitismo intestinal em trabalhadores de restaurantes e bares da cidade e arredores de Maputo, 1993. Revista Médica de Moçambique.1995 Mar-Jun:6(1–2):9–13.
- 23. Gujral L, Vaz R. Prevalência, comportamentos de risco e níveis de informação sobre a esquistossomose urinária em escolares da Área de Saúde 1° de Junho, na Cidade de Maputo, Moçambique. Cad. Saúde Pública. 2000 Jan-Mar:16(1):43–50.
- 24. Casmo V, Augusto G, Nala R, Sabonete A, Carvalho-Costa FA. The effect of hookworm infection and urinary schistosomiasis on blood hemoglobin concentration of schoolchildren living in northern Mozambique. Rev Inst Med Trop Sao Paulo. 2014 May-Jun;56(3):219–24. pmid:24879000
- 25. Shen Y, King CH, Binder S, Zhang F, Whalen CC, Evan Secor W, et al. Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries. BMC Infect Dis. 2017 Sep 29;17(1):652. pmid:28962552.
- 26. Phillips AE, Gazzinelli-Guimarães PH, Aurelio HO, Dhanani N, Ferro J, Nala R, et al. Urogenital schistosomiasis in Cabo Delgado, northern Mozambique: baseline findings from the SCORE study. Parasit Vectors. 2018 Jan 10;11(1):30. pmid:29316983.
- 27. Santano R, Rubio R, Grau-Pujol B, Escola V, Muchisse O, Cuamba I, et al. Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique. PLoS Negl Trop Dis. 2022 Jun 21;16(6):e0010138. pmid:35727821.
- 28. Augusto G, Nalá R, Casmo V, Sabonete A, Mapaco L, Monteiro J. Geographic distribution and prevalence of schistosomiasis and soil-transmitted helminths among schoolchildren in Mozambique. Am J Trop Med Hyg. 2009 Nov;81(5):799–803. pmid:19861614.
- 29. King CH. Parasites and poverty: the case of schistosomiasis. Acta Trop. 2010 Feb;113(2):95–104. Epub 2009 Dec 4. pmid:19962954.
- 30. Adenowo AF, Oyinloye BE, Ogunyinka BI, Kappo AP. Impact of human schistosomiasis in sub-Saharan Africa. Braz J Infect Dis. 2015 Mar-Apr;19(2):196–205. Epub 2015 Jan 27. pmid:25636189.
- 31. King CH, Dangerfield-Cha M. The unacknowledged impact of chronic schistosomiasis. Chronic Illn. 2008 Mar;4(1):65–79. pmid:18322031.
- 32. Rinaldo D, Perez-Saez J, Vounatsou P, Utzinger J, Arcand JL. The economic impact of schistosomiasis. Infect Dis Poverty. 2021 Dec 13;10(1):134. pmid:34895355.
- 33. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D. Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop. 2003 May;86(2–3):125–39. pmid:12745133.
- 34.
World Health Organization. The Expert Committee on Prevention and Control of Schistosomiasis and Soil-transmitted Helminthiasis. Current estimated total number of individuals with morbidity and mortality due to Schistosomiasis Haematobium and S. Mansoni infection in Sub-Saharan Africa [internet]. Geneva: World Health Organization; 2024. [cited 2024 Jun 26] Available from: https://www.who.int/teams/control-of-neglected-tropical-diseases/schistosomiasis/epidemiology
- 35.
Direção Nacional de Saúde Pública. Plano Nacional Integrado de Controlo das Doenças Tropicais Negligenciadas (2013–2017). Maputo: Ministério da Saúde da República de Moçambique; 48 p.
- 36. Bélard S, Tamarozzi F, Bustinduy AL, Wallrauch C, Grobusch MP, Kuhn W et al. Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases—A Review of Applications and Perspectives. Am J Trop Med Hyg. 2016 Jan;94(1):8–21. Epub 2015 Sep 28. pmid:26416111.
- 37. Brunetti E, Heller T, Richter J, Kaminstein D, Youkee D, Giordani MT, et al. Application of Ultrasonography in the Diagnosis of Infectious Diseases in Resource-Limited Settings. Curr Infect Dis Rep. 2016 Jan;18(2):6. pmid:26781324.
- 38. Fentress M, Heyne TF, Barron KR, Jayasekera N. Point-of-Care Ultrasound in Resource-Limited Settings: Common Applications. South Med J. 2018 Jul;111(7):424–433. pmid:29978229.
- 39. Kaminstein D, Heller T, Tamarozzi F. Sound Around the World: Ultrasound for Tropical Diseases. Infect Dis Clin North Am. 2019 Mar;33(1):169–195. pmid:30712760.
- 40. Santos J, Chaves J, Araújo H, Vale N, Costa JM, Brindley PJ, et al. Comparison of findings using ultrasonography and cystoscopy in urogenital schistosomiasis in a public health centre in rural Angola. S Afr Med J. 2015 Apr;105(4):312–5. pmid:26294877.
- 41. Remppis J, Verheyden A, Bustinduy AL, Heller T, García-Tardón N, Manouana GP, et al. Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)-pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings. Trans R Soc Trop Med Hyg. 2020 Jan 6;114(1):38–48. pmid:31735956.
- 42. Rey L. Prevenção dos riscos para a saúde decorrentes dos empreendimentos hidráulicos. Revista Médica de Moçambique.1982 Aug:1(2):55–62.
- 43. Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J. Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis. 2006 Jul;6(7):411–25. pmid:16790382.
- 44.
INDEPTH Network. Mozambique—Chokwe Health Research and Training Centre INDEPTH Core Dataset 2010–2016. Ghana: INDEPTH Data Repository, 2019 [cited 2024 Jun 26]. 19p. Report no.: MZ021.CMD2016.v2. Available from: https://www.indepth-ishare.org/index.php/catalog/176
- 45.
World Health Organization. Vaccination Coverage Cluster Surveys: Reference Manual. Geneva: World Health Organization; 2018 (WHO/IVB/18.09). Licence: CC BY-NC-SA 3.0 IGO.
- 46.
Chitsulo L, Lengeler C, Jennifer M. The schistosomiasis manual: a guide for the rapid identification of communities with a high prevalence of urinary schistosomiasis for district health management teams, diseases control programme managers and community health workers; Geneva: World Health Organization; 1995. [cited 2024 Jun 26]. Available from: https://iris.who.int/handle/10665/59004
- 47. Lengeler C, Utzinger J, Tanner M. Questionnaires for rapid screening of schistosomiasis in sub-Saharan Africa. Bull World Health Organ. 2002;80(3):235–42. pmid:11984610.
- 48. Yang F, Tan XD, Liu B, Yang C, Ni ZL, Gao XD et al. Meta-analysis of the diagnostic efficiency of the questionnaires screening for schistosomiasis. Parasitol Res. 2015 Sep;114(9):3509–19. Epub 2015 Jun 28. pmid:26122990
- 49. World Health Organization. Basic laboratory methods in medical parasitology. Geneva: World Health Organization; 1991. [cited 2024 Jun 26]. Available from: https://iris.who.int/handle/10665/40793
- 50. Katz N, Chaves A, Pellegrino J. A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1972 Nov-Dec;14(6):397–400. pmid:4675644.
- 51. Sandoval N, Siles-Lucas M, Lopez Aban J, Pérez-Arellano JL, Gárate T, Muro A. Schistosoma mansoni: a diagnostic approach to detect acute schistosomiasis infection in a murine model by PCR. Exp Parasitol. 2006 Oct;114(2):84–8. Epub 2006 Mar 29. pmid:16571353.
- 52. Kato-Hayashi N, Kirinoki M, Iwamura Y, Kanazawa T, Kitikoon V, Matsuda H, et al. Identification and differentiation of human schistosomes by polymerase chain reaction. Exp Parasitol. 2010 Mar;124(3):325–9. Epub 2009 Dec 3. pmid:19948171.
- 53.
Richter J, Hatz C, Campagne G, Bergquist NR, Jenkins JM. Ultrasound in schistosomiasis: a practical guide to the standard use of ultrasonography for assessment of schistosomiasis-related morbidity: Second international workshop, October 22–26 1996, Niamey, Niger. Geneve: World Health Organization; 2000. 49 p. Report No.: DR/STR/SCH/00.1
- 54. el Scheich T, Holtfreter MC, Ekamp H, Singh DD, Mota R, Hatz C, et al. The WHO ultrasonography protocol for assessing hepatic morbidity due to Schistosoma mansoni. Acceptance and evolution over 12 years. Parasitol Res. 2014 Nov;113(11):3915–25. Epub 2014 Sep 27. Erratum in: Parasitol Res. 2015 Jan;114(1):347. pmid:25260691.
- 55. Akpata R, Neumayr A, Holtfreter MC, Krantz I, Singh DD, Mota R et al. The WHO ultrasonography protocol for assessing morbidity due to Schistosoma haematobium. Acceptance and evolution over 14 years. Systematic review. Parasitol Res. 2015 Apr;114(4):1279–89. Epub 2015 Feb 25. Erratum in: Parasitol Res. 2015 May;114(5):2045–6. pmid:25711148.
- 56. Grimes JE, Croll D, Harrison WE, Utzinger J, Freeman MC, Templeton MR. The roles of water, sanitation and hygiene in reducing schistosomiasis: a review. Parasit Vectors. 2015 Mar 13;8:156. pmid:25884172.
- 57. Rassi C, Martin S, Graham K, de Cola MA, Christiansen-Jucht C, Smith LE et al. Knowledge, attitudes and practices with regard to schistosomiasis prevention and control: Two cross-sectional household surveys before and after a Community Dialogue intervention in Nampula province, Mozambique. PLoS Negl Trop Dis. 2019 Feb 7;13(2):e0007138. pmid:30730881.
- 58. Cavalcanti MG, Silva LF, Peralta RH, Barreto MG, Peralta JM. Schistosomiasis in areas of low endemicity: a new era in diagnosis. Trends Parasitol. 2013 Feb;29(2):75–82. Epub 2013 Jan 3. pmid:23290589.
- 59. Vaillant MT, Philippy F, Neven A, Barré J, Bulaev D, Olliaro PL et al. Diagnostic tests for human Schistosoma mansoni and Schistosoma haematobium infection: a systematic review and meta-analysis. Lancet Microbe. 2024 Apr;5(4):e366–e378. Epub 2024 Mar 9. pmid:38467130.
- 60. Koukounari A, Webster JP, Donnelly CA, Bray BC, Naples J, Bosompem K, et al. Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Am J Trop Med Hyg. 2009 Mar;80(3):435–41. pmid:19270295.
- 61. Fuss A, Mazigo HD, Tappe D, Kasang C, Mueller A. Comparison of sensitivity and specificity of three diagnostic tests to detect Schistosoma mansoni infections in school children in Mwanza region, Tanzania. PLoS One. 2018 Aug 22;13(8):e0202499. pmid:30133490.
- 62. Mesquita SG, Caldeira RL, Favre TC, Massara CL, Beck LCNH, Simões TCet al. Assessment of the accuracy of 11 different diagnostic tests for the detection of Schistosomiasis mansoni in individuals from a Brazilian area of low endemicity using latent class analysis. Front Microbiol. 2022 Dec 15;13:1048457. Erratum in: Front Microbiol. 2023 Nov 15;14:1331715. pmid:36590409.
- 63. Utzinger J, Becker SL, van Lieshout L, van Dam GJ, Knopp S. New diagnostic tools in schistosomiasis. Clin Microbiol Infect. 2015 Jun;21(6):529–42. Epub 2015 Apr 3. pmid:25843503.
- 64. Wiegand RE, Fleming FM, de Vlas SJ, Odiere MR, Kinung’hi S, King CH, et al. Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections. Lancet Glob Health. 2022 Sep;10(9):e1355–e1359. pmid:35961358.
- 65. Serieye J, Boisier P, Ravaoalimalala VE, Ramarokoto CE, Leutscher P, Esterre P, et al. Schistosoma haematobium infection in western Madagascar: morbidity determined by ultrasonography. Trans R Soc Trop Med Hyg. 1996 Jul-Aug;90(4):398–401. pmid:8882187.
- 66. King CH. Ultrasound monitoring of structural urinary tract disease in Schistosoma haematobium infection. Mem Inst Oswaldo Cruz. 2002;97 Suppl 1:149–52. pmid:12426610.
- 67. Salas-Coronas J, Vázquez-Villegas J, Lozano-Serrano AB, Soriano-Pérez MJ, Cabeza-Barrera I, Cabezas-Fernández MT, Villarejo-Ordóñez A, Sánchez-Sánchez JC, Abad Vivas-Pérez JI, Vázquez-Blanc S, Palanca-Giménez M, Cuenca-Gómez JA. Severe complications of imported schistosomiasis, Spain: A retrospective observational study. Travel Med Infect Dis. 2020 May-Jun;35:101508. Epub 2019 Nov 5. pmid:31704484.
- 68. Castillo-Fernández N, Soriano-Pérez MJ, Lozano-Serrano AB, Sánchez-Sánchez JC, Villarejo-Ordóñez A, Cuenca-Gómez JA, et al. Usefulness of ultrasound in sub-Saharan patients with a serological diagnosis of schistosomiasis. Infection. 2021 Oct;49(5):919–926. Epub 2021 May 4. pmid:33948875.
- 69. Botelho MC, Figueiredo J, Alves H. Bladder cancer and urinary Schistosomiasis in Angola. J Nephrol Res. 2015 Jun;1(1):22–24. pmid:26167543.
- 70.
World Health Organization. The control of schistosomiasis. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1985;728:1–113. pmid:3938106.
- 71. Bogoch II, Andrews JR, Dadzie Ephraim RK, Utzinger J. Simple questionnaire and urine reagent strips compared to microscopy for the diagnosis of Schistosoma haematobium in a community in northern Ghana. Trop Med Int Health. 2012 Oct;17(10):1217–21. Epub 2012 Aug 5. pmid:22863035.
- 72.
World Health Organization. WHO guideline on control and elimination of human schistosomiasis. Geneva: World Health Organization; 2022. [cited 2024 Jun 26]. Available from: https://iris.who.int/bitstream/handle/10665/351856/9789240041608-eng.pdf?sequence=1
- 73. UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases & Red Urine Study Group. Iden tification of high-risk communities for schistosomiasis in Africa:a multicountry study; 1995. 83 p.
- 74. Mafe MA, von Stamm T, Utzinger J, N’Goran EK. Control of urinary schistosomiasis: an investigation into the effective use of questionnaires to identify high-risk communities and individuals in Niger State, Nigeria. Trop Med Int Health. 2000 Jan;5(1):53–63. pmid:10672206.
- 75. Lima e Costa MF, Rocha RS, Firmo JO, Guerra HL, Passos VA, Katz N. Questionnaires in the screening for Schistosoma mansoni infection: a study of socio demographic and water contact variables in four communities in Brazil. Rev Inst Med Trop Sao Paulo. 1998 Mar-Apr;40(2):93–9. pmid:9755562.
- 76. Fürst T, Ouattara M, Silué KD, N’Goran DN, Adiossan LG, Bogoch II, et al. Scope and Limits of an anamnestic questionnaire in a control-induced low-endemicity helminthiasis setting in south-central Côte d’Ivoire. PLoS One. 2013 Jun 3;8(6):e64380. pmid:23755120.
- 77. Brooker S, Kabatereine NB, Gyapong JO, Stothard JR, Utzinger J. Rapid mapping of schistosomiasis and other neglected tropical diseases in the context of integrated control programmes in Africa. Parasitology. 2009 Nov;136(13):1707–18. Epub 2009 May 19. pmid:19450373.
- 78. King CH, Bertsch D. Meta-analysis of urine heme dipstick diagnosis of Schistosoma haematobium infection, including low-prevalence and previously-treated populations. PLoS Negl Trop Dis. 2013 Sep 12;7(9):e2431. pmid:24069486.
- 79. Knopp S, Ame SM, Hattendorf J, Ali SM, Khamis IS, Bakar F et al. Correction to: Urogenital schistosomiasis elimination in Zanzibar: accuracy of urine filtration and haematuria reagent strips for diagnosing light intensity Schistosoma haematobium infections. Parasit Vectors. 2019 Mar 28;12(1):149. Erratum for: Parasit Vectors. 2018 Oct 23;11(1):552. pmid:30922376.