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Persistent Urogenital Schistosomiasis and Its Associated Morbidity in Endemic Communities within Southern Ghana: Suspected Praziquantel Resistance or Reinfection?

ABSTRACT: BACKGROUND:schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The current study, therefore, assessed whether persistent schistosomiasis, with its associated morbidity among children living in endemic areas within the Greater Accra Region of Ghana, is as a result of reinfection or suspected praziquantel resistance. METHODOLOGY:this was a longitudinal study involving a baseline and follow-up sampling after praziquantel treatment. Urine samples were collected from school children (whose parents had also consented) for the detection of S. haematobium ova using a sedimentation technique. The morbidity parameters were examined with urine chemistry strips, as well as microscopy. Viability was assessed using a modified hatchability technique, vital staining (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) microscopy. Infected individuals were treated with a single dose of praziquantel (40mg/kg). Resampling to determine reinfection was done sixth months post-treatment, after evidence of total egg clearance. For possible resistance assessment, egg counts and viability testing were conducted on the positive samples at the baseline, as well as weekly post-treatment follow-ups for 12 weeks. RESULTS:out of the 420 school children sampled, 77 were initially positive but, after the sixth month sampling for reinfection assessment, eight out of the initial positives were infected again, giving a reinfection percentage of 10.4%. No suspected praziquantel resistance was recorded in the 21 positives detected out of the 360 sampled for suspected resistance assessment. The egg reduction rate increased weekly in the follow-up samples with a gradual reduction in the egg count. The study also recorded a gradual decrease in the percentage of live eggs after the first week; with all viability testing methods used complimenting each other. The morbidity parameters (proteinuria, haematuria and pyuria) changed between the baseline and post-treatment samples, eventually reducing to zero. CONCLUSIONS:the outcome of this study suggests that the persistent schistosomiasis, with its associated morbidity observed in these endemic communities, is not likely to be as a result of praziquantel resistance, but reinfection. Even though there was no suspected resistance observed in the study, there remains the need to continuously intensify the monitoring of praziquantel in other endemic communities.

SUBMITTER: Tetteh-Quarcoo PB

PROVIDER: S-EPMC7151560 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Persistent Urogenital Schistosomiasis and Its Associated Morbidity in Endemic Communities within Southern Ghana: Suspected Praziquantel Resistance or Reinfection?

Tetteh-Quarcoo Patience B PB Forson Peter O PO Amponsah Seth K SK Ahenkorah John J Opintan Japheth A JA Ocloo Janet E Y JEY Okine Esther N EN Aryee Robert R Afutu Emmanuel E Anang Abraham K AK Ayeh-Kumi Patrick F PF

Medical sciences (Basel, Switzerland) 20200210 1

<h4>Background</h4>schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The ...[more]

PMID: 32050572

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Project description:Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.

Project description:BackgroundIn light of the shift to aiming for schistosomiasis elimination, the following are needed: data on reinfection patterns, participation, and sample submission adherence of all high-risk age groups to intervention strategies. This study was conducted to assess prevalence, reinfections along with consecutive participation, sample submission adherence, and effect of treatment on schistosomiasis prevalence in children aged five years and below in an endemic district in Zimbabwe, over one year.MethodsThe study was conducted from February 2016-February 2017 in Madziwa area, Shamva district. Following community mobilisation, mothers brought their children aged 5 years and below for recruitment at baseline and also urine sample collection at baseline, 3, 6, 9 and 12 months follow up surveys. At each time point, urine was tested for urogenital schistosomiasis by urine filtration and children found positive received treatment. Schistosoma haematobium prevalence, reinfections as well as children participation, and urine sample submission at each visit were assessed at each time point for one year.ResultsOf the 535 children recruited from the five communities, 169 (31.6%) participated consecutively at all survey points. The highest mean number of samples submitted was 2.9 among communities and survey points. S. haematobium prevalence significantly reduced from 13.3% at baseline to 2.8% at 12 months for all participants and from 24.9% at baseline to 1.8% at 12 months (P < 0.001) for participants coming at all- time points. Among the communities, the highest baseline prevalence was found in Chihuri for both the participants coming consecutively (38.5%, 10/26) and all participants (20.4%, 21/103). Reinfections were significantly high at 9 months follow up survey (P = 0.021) and in Mupfure (P = 0.003). New infections significantly decreased over time (P < 0.001). Logistic regression analysis showed that the risk of acquiring schistosomiasis was high in some communities (P < 0.05).ConclusionsS. haematobium infections and reinfections are seasonal and depend on micro-geographical settings. The risk of being infected with schistosomes in pre-school aged children increases with increasing age. Sustained treatment of infected individuals in a community reduces prevalence overtime. Participation compliance at consecutive visits and sample submission adherence are important for effective operational control interventions.

Project description:In Sub-Saharan Africa, urogenital schistosomiasis remains a significant public health problem, causing 150.000 deaths/year with approximately 112 million cases diagnosed. The Niakhar district is a disease hotspot in central Senegal where transmission occurs seasonally with high prevalences. The aim of this study was to determine the effect of annual treatment over 3 years on the seasonal transmission dynamics of S. haematobium in 9 villages in the Niakhar district. Adults and children aged between 5 and 60 years were surveyed from 2011 to 2014. Urine samples were collected door-to-door and examined for S. haematobium eggs at baseline in June 2011, and all participants were treated in August 2011 with PZQ (40 mg/kg). After this initial examination, evaluations were conducted at 3 successive time points from September 2011 to March 2014, to measure the efficacy of the annual treatments and the rates of reinfection. Each year, during the transmission period, from July to November-December, malacological surveys were also carried out in the fresh water bodies of each village to evaluate the infestation of the snail intermediate hosts. At baseline, the overall prevalence of S. haematobium infection was 57.7%, and the proportion of heavy infection was 45.3%, but one month after the first treatment high cure rates (92.9%) were obtained. The overall infection prevalence and proportion of heavy infection intensities were drastically reduced to 4.2% and 2.3%, respectively. The level of the first reinfection in February-March 2012 was 9.5%. At follow-up time points, prevalence levels varied slightly between reinfection and treatment from 9.5% in June 2012 to 0.3% in March 2013, 11.2 in June 2013, and 10.1% April 2014. At the end of the study, overall prevalence was significantly reduced from 57.7% to 10.1%. The overall rate of infested Bulinid snails was reduced after repeated treatment from 0.8% in 2012 to 0.5% in 2013. Repeated annual treatments are suggested to have a considerable impact on the transmission dynamics of S. haematobium in Niakhar, due to the nature of the epidemiological system with seasonal transmission. Thus, to maintain this benefit and continue to reduce the morbidity of urogenital schistosomiasis, other approaches should be integrated into the strategy plans of the National program to achieve the goal of urogenital schistosomiasis elimination in seasonal foci in Senegal.

Project description:BackgroundIn sub-Saharan Africa, co-morbidity with malaria, schistosomiasis, and soil transmitted helminths (STH) is common among young children. The current study investigated malaria, urinary schistosomiasis and their co-infection and anemia among school-age children in an endemic community, Nakolo in the Kassena-Nankana East District of northern Ghana.MethodsA cross-sectional survey of 336 school-age children, 5-16 years was undertaken. Urine samples were examined for Schistosoma haematobium ova using microscopy. Finger prick blood samples were examined for Plasmodium parasites using microscopy and haemoglobin concentration measured with HemoCue Hb301 photometer.ResultsThe mean age was 10.52 (Standard deviation: ±2.27; range: 5-16 years), of which 50.6% (170/336) were males. The overall prevalence of urinary schistosomiasis and Plasmodium (P.) falciparum was 12.8% (43/336) and 37.8% (127/336), respectively with 6.0% (20/336) coinfection. Participants with only P. falciparum infection had 17.8% (19/107) of moderate anemia whilst 21.7% (5/23) of children infected with only S. haematobium had moderate anemia and 4.3% (1/23) had severe anemia. 5.0 % (1/20) of moderate anemia was observed in concurrent infections of P. falciparum and S. haematobium. Use of open water bodies was associated with increased risk of S. haematobium infection (OR = 1.21; 95% CI = [1.06-1.39]; p = 0.001), with females being at reduced risk (OR = 0.93; 95%CI = [0.87-0.99]; p = 0.005). Absence of self-reported haematuria had 0.81 times reduced odds of S. haematobium infection (OR = 0.81; 95%CI = [0.74-0.87]; p < 0.001).ConclusionThis study has revealed that urinary schistosomiasis remains prevalent in Kassena-Nankana East district and suggests that urinary schistosomiasis may contribute to moderate anemia among school-age children as compared to asymptomatic malaria infection. These findings call for an evaluation of the annual mass drug administration of Praziquantel among in-school children to ascertain its impact on urinary schistosomiasis prevalence across the district.

Project description:BackgroundSeveral studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤ 5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6-10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity.Methods/principal findingsA comparative cross-sectional study was conducted to evaluate the performance of currently available POC morbidity diagnostic tools on Zimbabwean children aged 1-5 years (n=104) and 6-10 years (n=194). Morbidity was determined using the POC diagnostics questionnaire-based reporting of haematuria and dysuria, clinical examination, urinalysis by dipsticks, and urine albumin-to-creatinine ratio (UACR). Attributable fractions were used to quantify the proportion of morbidity attributable to S. haematobium infection. Based on results of attributable fractions, UACR was identified as the most reliable tool for detecting schistosome-related morbidity, followed by dipsticks, visual urine inspection, questionnaires, and lastly clinical examination. The results of urine dipstick attributes showed that proteinuria and microhaematuria accounted for most differences between schistosome egg-positive and negative children (T=-50.1; p<0.001). These observations were consistent in preschool vs. primary school-aged children.Conclusions/significancePreschool-aged children in endemic areas can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. UACR for detecting albuminuria is recommended as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in children in the field. The use of dipstick microhaematuria and proteinuria as additional indicators of schistosome-related morbidity would improve the estimation of disease burden in young children.

Project description:BackgroundSub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon.MethodsEligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR).ResultsA total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%.ConclusionsThe prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013.

Project description:BackgroundIn many parts of sub-Saharan Africa, urogenital and intestinal schistosomiasis co-occur, and mixed species infections containing both Schistosoma haematobium and S. mansoni can be common. During co-infection, interactions between these two species are possible, yet the extent to which such interactions influence disease dynamics or the outcome of control efforts remains poorly understood.Methodology/principal findingsHere we analyse epidemiological data from three West African countries co-endemic for urogenital and intestinal schistosomiasis (Senegal, Niger and Mali) to test whether the impact of praziquantel (PZQ) treatment, subsequent levels of re-infection or long-term infection dynamics are altered by co-infection. In all countries, positive associations between the two species prevailed at baseline: infection by one species tended to predict infection intensity for the other, with the strength of association varying across sites. Encouragingly, we found little evidence that co-infection influenced PZQ efficacy: species-specific egg reduction rates (ERR) and cure rates (CR) did not differ significantly with co-infection, and variation in treatment success was largely geographical. In Senegal, despite positive associations at baseline, children with S. mansoni co-infection at the time of treatment were less intensely re-infected by S. haematobium than those with single infections, suggesting competition between the species may occur post-treatment. Furthermore, the proportion of schistosome infections attributable to S. mansoni increased over time in all three countries examined.Conclusions/significanceThese findings suggest that while co-infection between urinary and intestinal schistosomes may not directly affect PZQ treatment efficacy, competitive interspecific interactions may influence epidemiological patterns of re-infection post-treatment. While re-infection patterns differed most strongly according to geographic location, interspecific interactions also seem to play a role, and could cause the community composition in mixed species settings to shift as disease control efforts intensify, a situation with implications for future disease management in this multi-species system.

Dataset Information

Persistent Urogenital Schistosomiasis and Its Associated Morbidity in Endemic Communities within Southern Ghana: Suspected Praziquantel Resistance or Reinfection?

Publications

Persistent Urogenital Schistosomiasis and Its Associated Morbidity in Endemic Communities within Southern Ghana: Suspected Praziquantel Resistance or Reinfection?

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