Search

Background Individuals living in Schistosoma haematobium endemic areas are often at risk of having other communicable diseases simultaneously. This usually creates diagnostic difficulties leading to misdiagnosis and overlooking of schistosomiasis infection. In this study we investigated the prevalence and severity of coinfections in pre-school age children and further investigated associations between S. haematobium prevalence and under 5 mortality. Methods A community based cross-sectional survey was conducted in Shamva District, Zimbabwe. Using random selection, 465 preschool age children (1–5 years of age) were enrolled through clinical examination by two independent clinicians for the following top morbidity causing conditions: respiratory tract infections, dermatophytosis, malaria and fever of unknown origin. The conditions and their severe sequels were diagnosed as per approved WHO standards. S. haematobium infection was diagnosed by urine filtration and the children were screened for conditions common in the study area which included HIV, tuberculosis, malnutrition and typhoid. Data was analysed using univariate and multinomial regression analysis and relative risk (RR) calculated. Results Prevalence of S. haematobium was 35% (145). The clinical conditions assessed had the following prevalence in the study population: upper respiratory tract infection 40% (229), fever of unknown origin 45% (189), dermatophytosis 18% and malaria 18% (75). The odds of co-infections observed with S. haematobium infection were: upper respiratory tract infection aOR = 1.22 (95% CI 0.80 to 1.87), dermatophytosis aOR = 4.79 (95% CI 2.78 to 8.25), fever of unknown origin aOR = 10.63 (95% CI 6.48–17.45) and malaria aOR = 0.91 (95% CI 0.51 to1.58). Effect of schistosomiasis coinfection on disease progression based on the odds of the diseases progressing to severe sequalae were: Severe pneumonia aOR = 8.41 (95% CI 3.09–22.93), p p = 0.02, severe dermatophytosis aOR = 20.3 (95% CI 4.78–83.20):p = 0.03, and fever of unknown origin aOR = 1.62 (95%CI 1.56–4.73), p = 0.02. Conclusion This study revealed an association between schistosomiasis and the comorbidity conditions of URTI, dermatophytosis, malaria and FUO in PSAC living in a schistosomiasis endemic area. A possible detrimental effect where coinfection led to severe sequels of the comorbidity conditions was demonstrated. Appropriate clinical diagnostic methods are required to identify associated infectious diseases and initiate early treatment of schistosomiasis and co-infections in PSAC.

Background Schistosomiasis is known to induce inflammatory immune responses. C-reactive protein (CRP), resistin and P-selectin are serological inflammatory markers that rise during the acute stages of infection. Here, we propose such inflammatory biomarkers have a potential for use in urogenital schistosomiasis diagnostic screening for exposure and infection in preschool-aged children. Methods As part of a larger study on urogenital schistosomiasis, 299 preschool children aged 1–5 years were included in this cross-sectional study. Parasitological diagnosis was conducted using urine filtration for Schistosoma haemtobium infection, and Kato Katz for S. mansoni infection. Serum levels of P-selectin, resistin, CRP, and antibodies against S. haematobium cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP) were measured by ELISA. Results Of the 299 participants, 14% were egg positive for S. haematobium. Serology showed 46 and 9% of the participants to have been exposed to S. haematobium cercarial antigens and adult worm antigens, respectively. Levels of P-selectin were significantly higher in participants infected with S. haematobium (egg-positive) than in uninfected participants (p = 0.001). Levels of P-selectin were also higher in those exposed to cercarial antigen than in unexposed participants (p = 0.019). There was a positive correlation between P-selectin and infection intensity (r = 0.172; p = 0.002), as well as with IgM responses to CAP and SWAP (r = 0.183; p = 0.001); (r = 0.333; p r = 0.133; p = 0.029) while resistin correlated with IgM responses to CAP and SWAP (r = 0.127; p = 0.016); (r = 0.197; p = 0.0004). CRP levels were higher in those exposed to cercarial and adult worm antigens than unexposed participants (p = 0.035); (p = 0.002) respectively, while resistin was higher in participants exposed to cercarial antigen than unexposed participants (p = 0.024). Conclusion In this preschool population, P-selectin is significantly associated with urogenital schistosome infection and intensity; hence a potential biomarker for infection diagnosis and disease monitoring. The inflammatory biomarkers (P-selectin, Resistin and CRP) were significantly higher in participants exposed to cercarial antigens than unexposed individuals indicating an underlying inflammatory environment.

Introduction Prompt diagnosis of acute schistosomiasis benefits the individual and provides opportunities for early public health intervention. In endemic areas schistosomiasis is usually contracted during the first 5 years of life, thus it is critical to look at how the infection manifests in this age group. The aim of this study was to describe the prodromal signs and symptoms of early schistosomiasis infection, correlate these with early disease progression and risk score to develop an easy to use clinical algorithm to identify early Schistosoma haematobium infection cases in resource limited settings. Methodology Two hundred and four, preschool age children who were lifelong residence of a schistosomiasis endemic district and at high risk of acquiring schistosomiasis were followed up from July 2019 to December 2019, during high transmission season. The children received interval and standard full clinical evaluations and laboratory investigations for schistosomiasis by clinicians blinded from their schistosomiasis infection status. Diagnosis of S. haematobium was by urine filtration collected over three consecutive days. Signs and symptoms of schistosomiasis at first examination visit were compared to follow-up visits. Signs and symptoms common on the last schistosomiasis negative visit (before a subsequent positive) were assigned as early schistosomiasis infection (ESI), after possible alternative causes were ruled out. Logistic regression identified clinical predictors. A model based score was assigned to each predictor to create a risk for every child. An algorithm was created based on the predictor risk scores and validated on a separate cohort of 537 preschool age children. Results Twenty-one percent (42) of the participants were negative for S. haematobium infection at baseline but turned positive at follow-up. The ESI participants at the preceding S. haematobium negative visit had the following prodromal signs and symptoms in comparison to non-ESI participants; pruritic rash adjusted odds ratio (AOR) = 21.52 (95% CI 6.38–72.66), fever AOR = 82 (95% CI 10.98–612), abdominal pain AOR = 2.6 (95% CI 1.25–5.43), pallor AOR = 4 (95% CI 1.44–11.12) and a history of facial/body swelling within the previous month AOR = 7.31 (95% CI 3.49–15.33). Furthermore 16% of the ESI group had mild normocytic anaemia, whilst 2% had moderate normocytic anaemia. A risk score model was created using a rounded integer from the relative risks ratios. The diagnostic algorithm created had a sensitivity of 81% and a specificity of 96.9%, Positive predictive value = 87.2% and NPV was 95.2%. The area under the curve for the algorithm was 0.93 (0.90–0.97) in comparison with the urine dipstick AUC = 0.58 (0.48–0.69). There was a similar appearance in the validation cohort as in the derivative cohort. Conclusion This study demonstrates for the first time prodromal signs and symptoms associated with early S. haematobium infection in pre-school age children. These prodromal signs and symptoms pave way for early intervention and management, thus decreasing the harm of late diagnosis. Our algorithm has the potential to assist in risk-stratifying pre-school age children for early S. haematobium infection. Independent validation of the algorithm on another cohort is needed to assess the utility further., Author summary Schistosoma haematobium causes urogenital infection and in endemic areas schistosomiasis is usually contracted during the first 5 years of life, thus it is critical to look at how the infection manifests in this age group. Prompt diagnosis of acute schistosomiasis is required to benefit the individuals and provide opportunities for early treatment and public health intervention. The study examined symptoms that correlated with early disease progression and risk scored to develop an easy to use clinical algorithm to identify early S. haematobium infection cases. The children received standard full clinical evaluations by clinicians who were blinded from schistosomiasis diagnosis by parasitological examination. An algorithm was created based on the predictor risk scores and participants had the following prodromal signs and symptoms; pruritic rash, abdominal pain, pallor, abdominal pain, inguinal lymphadenopathy and a history of facial/body swelling within the previous month. A risk score model, diagnostic algorithm, was created that compared to urine dipstick and parasitology. This study demonstrates the clinical signs and symptoms associated with early S. haematobium infection in pre-school age children. These prodromal signs and symptoms pave way for early intervention and management, thus decreasing the harm of late diagnosis common in populations from endemic areas.

Background: Host genetic factors can influence susceptibility, morbidity and mortality from schistosomiasis. The study explored the association between single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10) and tumour necrosis factor alpha (TNF-α) promoter regions and susceptibility to Schistosoma haematobium infection. Methods: Urine specimens were collected from 361 primary school children aged 5–15 years from schistosomiasis endemic areas of Manicaland and Mashonaland central provinces. Schistosoma haematobium was diagnosed using the urine filtration method. Only 272 participants provided adequate blood for genotyping. Genotyping was performed using the amplification refractory mutation system-polymerase chain reaction. The association between IL-10 and TNF-α SNPs and S. haematobium infection was analysed using the chi-square test. Results: Schistosoma haematobium infection was confirmed in 26.8% of the participants. No significant difference in S. haematobium prevalence between men (51.6% of those infected) and women (48.4%) (χ 2 = 0.008, df = 1, p = 0.928) was observed. The total IL-10 -1082 G, IL-10 -819 C and TNF-α -308G allele distribution between S. haematobium infected and uninfected participants was 50.7% and 51.5% (χ 2 = 0.025, df = 1, p = 0.87), 54.3% and 60.6% (χ 2 = 1.187, df = 1, p = 0.187) and 82.1% and 80.9% (χ 2 = 0.099, df = 1, p = 0.753), respectively, and the differences were not significant. Conclusion: Interleukin-10 -1082 G/A, IL-10 -819 C/T and TNF-α -308 G/A SNPs were not significantly associated with susceptibility to S. haematobium infection. The prevalence of schistosomiasis is still in the moderate range and is similar in boys and girls.

Background Serological testing based on different antibody types are an alternative method being used to diagnose SARS-CoV-2 and has the potential of having higher diagnostic accuracy compared to the current gold standard rRT-PCR. Therefore, the objective of this review was to evaluate the diagnostic accuracy of IgG and IgM based point-of-care (POC) lateral flow immunoassay (LFIA), chemiluminescence enzyme immunoassay (CLIA), fluorescence enzyme-linked immunoassay (FIA) and ELISA systems that detect SARS-CoV-2 antigens. Method A systematic literature search was carried out in PubMed, Medline complete and MedRxiv. Studies evaluating the diagnostic accuracy of serological assays for SARS-CoV-2 were eligible. Study selection and data-extraction were performed by two authors independently. QUADAS-2 checklist tool was used to assess the quality of the studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model were performed to evaluate the diagnostic accuracy of the serological tests. Subgroup meta-analysis was performed to explore the heterogeneity. Results The pooled sensitivity for IgG (n = 17), IgM (n = 16) and IgG-IgM (n = 24) based LFIA tests were 0.5856, 0.4637 and 0.6886, respectively compared to rRT-PCR method. The pooled sensitivity for IgG (n = 9) and IgM (n = 10) based CLIA tests were 0.9311 and 0.8516, respectively compared to rRT-PCR. The pooled sensitivity the IgG (n = 10), IgM (n = 11) and IgG-IgM (n = 5) based ELISA tests were 0.8292, 0.8388 and 0.8531 respectively compared to rRT-PCR. All tests displayed high specificities ranging from 0.9693 to 0.9991. Amongst the evaluated tests, IgG based CLIA expressed the highest sensitivity signifying its accurate detection of the largest proportion of infections identified by rRT-PCR. ELISA and CLIA tests performed better in terms of sensitivity compared to LFIA. IgG based tests performed better compared to IgM except for the ELISA. Conclusions We report that IgG-IgM based ELISA tests have the best overall diagnostic test accuracy. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type independently. Given the poor performances of the current LFIA devices, there is a need for more research on the development of highly sensitivity and specific POC LFIA that are adequate for most individual patient applications and attractive for large sero-prevalence studies. Systematic review registration PROSPERO CRD42020179112

Background: Knowledge gaps exist between host genetic factors and susceptibility to schistosomiasis. Objective: This study determined cytokine levels and single nucleotide polymorphisms of tumour necrosis factor (TNF)-α (rs1800629) and interleukin (IL)-10 (rs1800871) and their possible impact on susceptibility to schistosomiasis in preschool-age children in the Madziva area of Shamva district, Mashonaland Central province, Zimbabwe. Methods: Urogenital schistosomiasis was diagnosed using the urine filtration method, while a sandwich enzyme-linked immunosorbent assay was used for cytokine level determination. The survey was done in August 2015 and reinfection levels post treatment were assessed at 3, 6 and 12 months. Amplification refractory mutation system polymerase chain reaction with visualisation on 2% agarose gel electrophoresis was used for genotyping. Results: Schistosomiasis prevalence was found to be 10.5% (59/563). Reinfections were detected in only six children at 3 months and only one was reinfected at 12 months. There were no significant differences in TNF-α-308 G/A allele or genotype frequencies between the Schistosoma haematobium infected participants (p = 0.360) and uninfected participants (p = 0.279). However, no children with the IL-10-819 TT genotype had schistosomiasis. The TNF-α GG genotype corresponded with significantly lower TNF-α levels when compared with the GA or AA genotypes (p 0.001), and TNF-α levels were significantly lower in infected children compared to uninfected children (p 0.001). Conclusion: Higher TNF-α levels and lower IL-10 levels are potentially protective against schistosomiasis infection. The IL-10-819 TT genotype is potentially protective against infection through its association with lower IL-10 levels.

IntroductionNeglected tropical diseases tend to cluster in the same poor populations and, to make progress with their control, they will have to be dealt with in an integrated manner. Peptide microarrays may be a solution to these problems, where diagnosis for co-infection can be detected simultaneously using the one tool. A meta-analysis using hierarchical models will be performed to assess the diagnostic accuracy of peptide microarrays for detecting schistosomiasis (Schistosoma mansoni and S. haematobium), soil-transmitted helminths (Trichuris trichiura, Ascaris lumbricoides and Necator americanus), trachoma (Chlamydia trachomatis), lymphatic filariasis (Wuchereria bancrofti) and onchocerciasis (Onchocerca volvulus) in people residing in sub-Saharan Africa.Methods and analysisA comprehensive search of the following databases will be performed: Cochrane Infectious Diseases Group Specialised Register, PubMed, EMBASE and The Web of Science. Studies comparing peptide microarrays with a reference standard from a random or consecutive series of patients will be included in the study. Two review authors will independently screen titles and abstracts for relevance, assess full-text articles for inclusion and carry out data extraction using a tailored data extraction form. The quality Assessment of Diagnostic Accuracy Studies-2 tool will be used to assess the quality of the selected studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model will be performed to evaluate the diagnostic accuracy of the peptide microarrays. Meta-regression analyses will be performed to investigate heterogeneity across studies.Ethics and disseminationThere is no requirement for ethical approval because the work will be carried out using previously published data, without human beings involvement. Findings will be disseminated through peer-reviewed publication and in conference presentations.PROSPERO registration numberCRD42020175145.

Background Schistosomiasis is a devastating parasitic disease. The mainstay of schistosomiasis control is by praziquantel treatment. The study aimed to determine benefits of annual chemotherapy of schistosomiasis on development of protective immunity in school children in a selected endemic rural area in Zimbabwe. Methods Urine specimens from 212 school children (7–13 years) were collected and examined to determine prevalence, intensity and reinfection of S.haematobium at baseline, 6 weeks and 2 years following annual rounds of praziquantel treatment. Blood samples from the participants were assayed for total and S. haematobium (Sh13)-specific antibodies before and 2 years after annual rounds of treatment. Results Annual treatment reduced the prevalence of S. haematobium infection (p

Infections caused by Plasmodium falciparum and P. vivax account for more than 90% of global malaria burden. Exposure to malaria parasite elicits immune responses during natural infection and it is generally believed that the immunity is not only stage specific but also species specific. However, partial genomic similarity for various antigens in different Plasmodium spp. raises the possibility of immunological cross-reactivity at the level of specific antigens. Serum samples collected from children who were permanent residents of a P. falciparum transmission area in Zimbabwe were screened for antibody reactivity against Pfs48/45, a P. falciparum gametocyte antigen and Pvs48/45, a P. vivax homolog of Pfs48/45 using ELISA. Western blotting was used to further confirm identity of the specific antibody reactivity to the Pfs48/45 and Pvs48/45 proteins. Pan Plasmodium PCR and nested PCR were used to confirm infection with the Plasmodium species. Twenty-seven percent (49/181) of the participants were found to be sero-positive for Pfs48/45 and 73% (n=36) of these Pfs48/45 positive sera also showed reactivity with Pvs48/45. Immune cross-reactivity revealed by ELISA was also confirmed by Western blot analysis using a panel of randomly selected 23 Pfs48/45 and Pvs48/45 ELISA positive samples. Nested PCR analysis of 27 blood samples randomly selected from the 36 that showed positive ELISA reactivity to both Pfs48/45 and Pvs48/45 antigens confirmed infection with P. falciparum and generalized absence of P. vivax except for a single sample which revealed PCR positivity for both P. vivax and P. falciparum. Our studies with sera samples from a predominantly P. falciparum transmission area in Zimbabwe suggest immunological cross-reactivity with Pvs48/45, thus raising the possibility of partial species cross-reactive immunity and possible cross-boosting of immunity during co-infection with P. falciparum and P. vivax.

Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6–16 years in Makoni district of Zimbabwe, an area of low to modest malaria transmission. Malaria infection was screened by microscopy, rapid diagnostic tests and finally using nested PCR. Plasma samples were tested for antibodies against recombinant Pfs48/45 and Pfs47 by ELISA. Corresponding serum samples were used to test for P. falciparum transmission reducing activity in Anopheles stephensi and An. gambiae mosquitoes using the membrane feeding assay. The prevalence of malaria diagnosed by rapid diagnostic test kit (Paracheck)™ was 1.7 %. However, of the randomly tested blood samples, 66% were positive by nested PCR. ELISA revealed prevalence (64% positivity at 1:500 dilution, in randomly selected 66 plasma samples) of antibodies against recombinant Pfs48/45 (mean A405nm = 0.53, CI=0 .46 to 0.60) and Pfs47 (mean A405nm= 0.91, CI=0.80to 1.02); antigens specific to the sexual stages. The mosquito membrane feeding assay demonstrated measurable transmission reducing ability of the samples that were positive for Pfs48/45 antibodies by ELISA. Interestingly, 3 plasma samples revealed enhancement of infectivity of P. falciparum in An. stephensi mosquitoes. These studies revealed the presence of antibodies with transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine.