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Combined rapid (TUBEX) test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

ABSTRACT: Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12) found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX) immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively). Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0%) or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6), respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid) if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA)--such specimens might have been storage-denatured (especially the older paratyphoid samples) or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera analysis was insightful, revealing 64% of typhoid patients who had no change in antibody titer over 4-16 days, and 14% with no IgM-IgG class-switching.

SUBMITTER: Yan M

PROVIDER: S-EPMC3174194 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Combined rapid (TUBEX) test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

Yan Meiying M Tam Frankie C H FC Kan Biao B Lim Pak Leong PL

PloS one 20110915 9

Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in pa ...[more]

PMID: 21935450

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Project description:PURPOSE OF REVIEW:Enteric fever remains a major global-health concern, estimated to be responsible for between 11.9 and 26.9 million cases annually. Long-term prevention of enteric fever will require improved access to safe drinking water combined with investment in sanitation and hygiene interventions. In the short-to-medium term, new control strategies for typhoid fever have arrived in the form of typhoid Vi-conjugate vaccines (TCVs), offering hope that disease control can be achieved in the near future. RECENT FINDINGS:The diagnosis of enteric fever is complicated by its nonspecific clinical presentation, coupled with the low sensitivity of commonly used diagnostics. Investment in diagnostics has the potential to improve management, to refine estimates of disease burden and to facilitate vaccine impact studies. A new generation of reliable, diagnostic tests is needed that are simultaneously accessible, cost-effective, sensitive, and specific. The emergence and global dissemination of multidrug-resistant, fluoroquinolone-resistant, and extensively drug-resistant (XDR) strains of Salmonella Typhi emphasizes the importance of continued surveillance and appropriate antibiotic stewardship, integrated into a global strategy to address antimicrobial resistance (AMR). Current empirical treatment guidelines are out of date and should be updated to respond to local trends in AMR, so as to guide treatment choices in the absence of robust diagnostics and laboratory facilities. In September 2017, the WHO Strategic Advisory Group of Experts (SAGE) immunization recommended the programmatic use of TCVs in high burden countries. Ongoing and future studies should aim to study the impact of these vaccines in a diverse range of setting and to support the deployment of TCVs in high-burden countries. SUMMARY:The advent of new generation TCVs offers us a practical and affordable public-health tool that - for the first time - can be integrated into routine childhood immunization programmes. In this review, we advocate for the deployment of TCVs in line with WHO recommendations, to improve child health and limit the spread of antibiotic-resistant S. Typhi.

Project description:BackgroundPrecise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.MethodsFrom September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid.FindingsA total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765-1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230-480) in Kathmandu and 268 (202-362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144-216) and 103 (85-126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107-154) in Bangladesh, 46 (34-62) and 81 (56-118) in the Nepal sites, and 23 (19-29) and 1 (1-1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised.InterpretationAcross diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines.FundingBill & Melinda Gates Foundation.

Project description:Typhoid fever is a common cause of fever in Cambodian children but diagnosis and treatment are usually presumptive owing to the lack of quick and accurate tests at an initial consultation. This study aimed to evaluate the cost-effectiveness of using a rapid diagnostic test (RDT) for typhoid fever diagnosis, an immunoglobulin M lateral flow assay (IgMFA), in a remote health centre setting in Cambodia from a healthcare provider perspective. A cost-effectiveness analysis (CEA) with decision analytic modelling was conducted. We constructed a decision tree model comparing the IgMFA versus clinical diagnosis in a hypothetical cohort with 1000 children in each arm. The costs included direct medical costs only. The eligibility was children (?14 years old) with fever. Time horizon was day seven from the initial consultation. The number of treatment success in typhoid fever cases was the primary health outcome. The number of correctly diagnosed typhoid fever cases (true-positives) was the intermediate health outcome. We obtained the incremental cost effectiveness ratio (ICER), expressed as the difference in costs divided by the difference in the number of treatment success between the two arms. Sensitivity analyses were conducted. The IgMFA detected 5.87 more true-positives than the clinical diagnosis (38.45 versus 32.59) per 1000 children and there were 3.61 more treatment successes (46.78 versus 43.17). The incremental cost of the IgMFA was estimated at $5700; therefore, the ICER to have one additional treatment success was estimated to be $1579. The key drivers for the ICER were the relative sensitivity of IgMFA versus clinical diagnosis, the cost of IgMFA, and the prevalence of typhoid fever or multi-drug resistant strains. The IgMFA was more costly but more effective than the clinical diagnosis in the base-case analysis. An IgMFA could be more cost-effective than the base-case if the sensitivity of IgMFA was higher or cost lower. Decision makers may use a willingness-to-pay threshold that considers the additional cost of hospitalisation for treatment failures.

Project description:The impact of temperature and rainfall on the occurrence of typhoid/paratyphoid fever are not fully understood. This study aimed to characterize the effect of daily ambient temperature and total rainfall on the incidence of typhoid/paratyphoid in a sub-tropical climate city of China and to identify the vulnerable groups for disease prevention. Daily notified typhoid/paratyphoid fever cases and meteorological data for Taizhou from 2005 to 2013 were extracted from the National Notifiable Disease Surveillance System and the Meteorological Data Sharing Service System, respectively. Distributed lag nonlinear model was used to quantify the association between daily mean temperature, total rainfall, and typhoid/paratyphoid fever. Subgroup analyses by gender, age, and occupation were conducted to identify the vulnerable groups. A total of 625 typhoid fever cases and 1,353 paratyphoid fever cases were reported during the study period. An increased risk of typhoid fever was detected with the increase of temperature (Each 2°C rise resulted in 6%, 95% [confidence interval] CI: 2-10% increase in typhoid cases), while the increased risk was associated with the higher temperature for paratyphoid (the highest cumulative risk of temperature was 33.40 [95% CI: 12.23-91.19] at 33°C). After the onset of mild precipitation, the relative risk of typhoid fever increased in a short-lasting and with a 13-26 days delay, and the risk was no significant after the continuous increase of precipitation (the highest cumulative risk of rainfall was 24.96 [95% CI: 4.54-87.21] at 100 mm). Whereas the risk of paratyphoid fever was immediate and long lasting, and increase rapidly with the increase of rainfall (each 100 mm increase was associated with 26% increase in paratyphoid fever cases). Significant temperature-typhoid/paratyphoid fever and rainfall-typhoid/paratyphoid fever associations were found in both genders and those aged 0-4 years old, 15-60 years old, farmers, and children. Characterized with a lagged, nonlinear, and cumulative effect, high temperature and rainfall could increase the risk of typhoid/paratyphoid fever in regions with a subtropical climate. Public health interventions such as early warning and community health education should be taken to prevent the increased risk of typhoid/paratyphoid fever, especially for the vulnerable groups.

Dataset Information

Combined rapid (TUBEX) test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

Publications

Combined rapid (TUBEX) test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

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