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
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.
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.
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.
Background Schistosomiasis is known to affect the cognitive functions of children, however, but there is paucity of information on its impact on early childhood development in developing countries where the disease is endemic. This study aimed at determining the effects of schistosomiasis due to Schistosoma haematobium on early childhood development in children below 5 years old from Murewa District, Zimbabwe, including the benefits of treatment. Methods Preschool age children (PSAC) under the age of 5 years were screened at baseline and at 6 months post-treatment for S. haematobium infections diagnosed using the urine filtration method. Cognitive domains were assessed using the Griffith Mental Developmental Scales III on 136 PSAC. Multivariate logistic regression was used to determine the level of association between S. haematobium infection and performance in the cognitive domains adjusting for confounding factors (i.e. nutrition, hemoglobin levels, gender and age). Median Development Quotient scores of each cognitive domain at baseline and at 6 months post-treatment were compared and quantified. Results After adjusting for confounding factors, PSAC infected with S. haematobium had greater odds of having lower scores in the Foundation of Learning Domain (OR = 3.9, p = 0.008), Language and Communication Domain (OR = 3.2, p = 0.017), Eye-Hand Coordination Domains (OR = 10.7, p = 0.001), Personal-Social-Emotional Domain (19.3, p = 0.001) and in the Overall General Development Domain (7.2, p = 0.011). Improvement of cognitive performance was observed at 6 months post treatment in the following Domains; Language and Communication Domain (p = 0.003), Eye-Hand Coordination Domain (p = 0.02) and General Development Domain (p = 0.006). Conclusion The study showed that S. haematobium infection in PSAC is associated with lower cognitive scores in the Foundation of Learning, Language and Communication, Eye-Hand Coordination, Personal-Social-Emotional and in the Overall General Development domains. Our results strengthen the call for inclusion of PSAC in routine deworming programs for the control of urinary schistosomiasis and the need to develop locally validated tools to monitor early child development in endemic areas where resources are limited.
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 Tumors are known to increase the risk of infections, more-so in the central nervous system where tumors may require insertion of surgical hardware/shunts such as in craniopharyngiomas. In contrast, our observation demonstrate that infections of surgical hardware are surprisingly scarce in craniopharyngioma cases. In this study, we explore the possibility of antimicrobial effects of craniopharyngioma cystic fluid. Methods The antibacterial effect of samples of craniopharyngioma cystic fluid against the selected human pathogens Escherichia. coli, S. aureus and S. pneumoniae was determined using the agar disc diffusion method. These results were compared with that of streptomycin and ampicillin. Results The samples of craniopharyngioma cystic fluid inhibited growth of gram-positive bacteria (S. aureus and S. pneumoniae) but not the gram-negative bacteria, E. coli. The samples showed highest zones of S. pneumoniae growth inhibition. Conclusion Craniopharyngioma cystic fluid demonstrated significant antibacterial properties against gram positive bacteria. More studies need to be carried out to further elucidate this unique finding. Conflicts of interest: Authors declare no conflict of interest Availability of Data Material: Raw data can be made available on request Code availability: Available on request Author's contribution: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Luxwell Jokonya, Tsungai Reid, Maritha Kasambala, Tariro Mduluza-Jokonya. The first draft of the manuscript was written by Luxwell Jokonya
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.
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