Clinical morbidity associated with Schistosoma haematobium infection in pre-school age children from an endemic district in Zimbabwe.

OBJECTIVE: To investigate Schistosoma haematobium morbidity in infected pre-school age children and establish their disease burden. METHODOLOGY: Pre-school age children (1-5 years) who were lifelong residents of the study area and had no other infections were included in the study. Participants underwent a physical examination with clinicians blinded to their infection status. Diagnosis of S. haematobium was by urine filtration. RESULTS: The prevalence of S. haematobium was 35.1% (146/416). The clinical features observed in patients with Schistosoma haematobium were as follows: wheezes (morbidity attributable factor (AF = 93.9%), haematuria (AF = 92.6%), ascites (AF = 91.5%), atopy (AF = 76.9%), inguinal lymphadenopathy (AF = 68.4%), stunting (AF = 38.2), malnutrition (MUAC)(AF = 20%) and weight for height scales (AF = 5%). Schistosoma. haematobium infected children were at greater odds ratio of presenting with inguinal lymphadenopathy (AOR)=99.2(95% CI 24.2 to 854.5), wheezes in the chest (AOR = 35.4 95% CI 15.3 to 94.2), Distended abdomen with ascites (AOR = 23.9 95% CI 11.4 to 54), haematuria (AOR = 12.6 95% CI 11.6 to 14.1), atopy history (AOR = 5.6 95% CI 1.85 to 20.2), malnutrition (AOR = 2.3 95% CI 1.4 to 3.2) and stunting (AOR = 1.9 95% CI 1.1 to2.7). CONCLUSION: The study is novel as it demonstrates for the first time clinical morbidity markers associated with S. haematobium infection in pre-school age children. Furthermore the study adds scientific evidence to the call for inclusion of pre-school age children in schistosomiasis control programmes. These morbidity markers highlight the need for early diagnosis and screening for S. haematobium in pre-school age children.

OBJECTIF: Etudier la morbidité de Schistosoma haematobium chez les enfants d'âge préscolaire infectés et établir sa charge de morbidité. MÉTHODOLOGIE: Les enfants d'âge préscolaire (1 à 5 ans) qui avaient toujours résidents de la zone d'étude et qui n'avaient pas d'autres infections ont été inclus dans l'étude. Les participants ont subi un examen physique avec des cliniciens en aveugle sur leur état d'infection. Le diagnostic de S. haematobium a été effectué par filtration d'urine. RÉSULTATS: La prévalence de S. haematobium était de 35,1% (146/416). Les caractéristiques cliniques observées chez les patients infectés par S. haematobium étaient: respiration sifflante (facteur attribuable à la morbidité (FA = 93,9%), hématurie (FA = 92,6%), ascite (FA = 91,5%), atopie (FA = 76,9%), lymphadénopathie inguinale (FA = 68,4%), retard de croissance ( AF = 38,2), malnutrition (MUAC) (AF = 20%) et poids pour les échelles de taille (AF = 5%). Les enfants infectés par S. haematobium présentaient un rapport de cotes plus élevé de présenter une lymphadénopathie inguinale (AOR) = 99,2 ; (IC95%: 24,2 à 854,5), respiration sifflante dans la poitrine (AOR = 35,4 ; IC95%: 15,3 à 94,2), abdomen distendu avec ascite (AOR = 23,9 ; IC95%: 11,4 à 54), hématurie (AOR = 12,6 ; IC95%: 11,6 à 14,1), antécédents d'atopie (AOR = 5,6 ; IC95%: 1,85 à 20,2), malnutrition (AOR = 2,3 ; IC95%: 1,4 à 3,2) et retard de croissance (AOR = 1,9 ; IC95%: 1,1 à 2,7). CONCLUSION: L'étude est nouvelle car elle démontre pour la première fois des marqueurs cliniques de morbidité associés à une infection à S. haematobium chez des enfants d'âge préscolaire. En outre, l'étude ajoute des données scientifiques à l'appel à l'inclusion des enfants d'âge préscolaire dans les programmes de lutte contre la schistosomiase. Ces marqueurs de morbidité mettent en évidence la nécessité d'un diagnostic précoce et d'un dépistage de S. haematobium chez les enfants d'âge préscolaire.

Association of Schistosoma haematobium infection morbidity and severity on co-infections in pre-school age children living in a rural endemic area in Zimbabwe.

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 < 0.0001, complicated malaria aOR = 7.09 (95% CI 1.51-33.39), 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.

Scoping review of the applications of peptide microarrays on the fight against human infections.

INTRODUCTION: This scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis. METHODS: Electronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: Ninety-five articles from 103 studies were included in the final data charting process. The majority (92. 0%) of the articles were published during 2010-2020 and were mostly from Europe (44.2%) and North America (34.7%). The findings were from the investigation of viral (45.6%), bacterial (32. 0%), parasitic (23.3%) and fungal (2. 0%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (77.7%) were related to mapping B-cell linear epitopes, 5.8% were on diagnostics, 5.8% reported on immunosignature characterisation and 8.7% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling. CONCLUSION: The most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.

Multiplex peptide microarray profiling of antibody reactivity against neglected tropical diseases derived B-cell epitopes for serodiagnosis in Zimbabwe.

INTRODUCTION: Peptides (B-cell epitopes) have broad applications in disease diagnosis and surveillance of pathogen exposure. In this framework, we present a pilot study to design and produce a peptide microarray for the integrated surveillance of neglected tropical diseases. The peptide microarray was evaluated against peptides derived from Ascaris lumbricoides, Necator americanus, Schistosoma haematobium, Schistosoma mansoni, Trichuris trichiura, Bacillus anthracis, Mycobacterium leprae, Wuchereria bancrofti, Rabies lyssavirus, Chlamydia trachomatis and Trypanosoma brucei. METHODS: S. haematobium was diagnosed using the urine filtration technique. S. mansoni, A. lumbricoides, N. americanus and T. trichiura were diagnosed using the Kato Katz and formal ether concentration techniques. Immunogenic peptides were retrieved from the Tackling Infection to Benefit Africa infectious diseases epitope microarray. Further peptides were predicted using ABCpred. IgG and IgM reactivity against the derived peptides were evaluated using peptide microarray multiplex immunoassays. Positive response was defined as fluorescence intensity ≥ 500 fluorescence units. Immunodominant peptides were identified using color-coded heat maps and bar graphs reflecting the obtained fluorescence signal intensities. Receiver Operating Characteristic analysis and Mann-Whitney-U test were performed to determine the diagnostic validity of the peptides. RESULTS: Species-specific responses with at least one peptide derived from each NTD pathogen were observed. The reactive peptides included; for S. haematobium, XP_035588858.1-206-220 and XP_035588858.1-206-220 immunodominant for IgG and IgM respectively, for S. mansoni, P20287.1-58-72 immunodominant for both antibodies and for T. trichiura, CDW52482.1-326-340 immunodominant for IgG and CDW57769.1-2017-2031 and CDW57769.1-1518-1532 immunodominant for IgM. According to ROC analysis most of the peptides selected were inaccurate; with AUC < 0.5. Some peptides had AUC values ranging from 0.5 to 0.5875 for both IgM and IgG suggesting no discrimination. CONCLUSION: Multiplex peptide microarrays are a valuable tool for integrated NTDs surveillance and for screening parasites exposure in endemic areas. Species sero-reactivity observed in the study maybe indicative of exposure to the different NTDs parasites. However, although peptides with the least cross reactivity were selected there is need to validate the sero-reactivity with recombinant antigens and immune-blotting techniques such as western blotting.

Truncal complex regional pain syndrome, myth or reality: Case report.

INTRODUCTION: Complex regional pain syndrome (CRPS) is an under diagonised, chronic pain condition commonly described occurring in the extremities. Its occurrence in the trunk is rarely reported and is thought by some to be non existent. CASE PRESENTATION: We report an unusual case of trunkul CRPS post appendectomy which presented with debilitating pain and review relevant literature. DISCUSSION AND CONCLUSION: We recommend that subsequent descriptions and diagnostic criteria should include the trunk as a site of occurrence of CRPS and not just the extremities. This will help reduce under diagnosis of this important condition.

Algorithm for diagnosis of early Schistosoma haematobium using prodromal signs and symptoms in pre-school age children in an endemic district in Zimbabwe.

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.

A systematic and meta-analysis review on the diagnostic accuracy of antibodies in the serological diagnosis of COVID-19.

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.