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Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates.

ABSTRACT: BACKGROUND:In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence. METHODS:We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower risk of disease than those who had blood drawn. We assessed clinical and demographic predictors of having blood taken for culture, and predictors of culture-positive results. Missing blood culture data were imputed using multiple imputations. RESULTS:During the first year of surveillance, 2392 fever presentations were recorded and 1615 (68%) of these had blood cultures. Children were more likely to have blood taken for culture if they were older, had fever for longer, a current temperature ?38 degrees, or if typhoid or a urinary tract infection were suspected. Based on imputation models, those with blood cultures were 1.87 times more likely to have blood culture-positive fever than those with missing data. CONCLUSION:Clinical opinion on the cause of the fever may play a large part in the decision to offer blood culture, regardless of study protocol. Crude typhoid incidence estimates should be adjusted for the proportion of cases that go undetected due to missing blood cultures while adjusting for the lower likelihood of culture-positivity in the group with missing data.

SUBMITTER: Voysey M

PROVIDER: S-EPMC6964825 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates.

Voysey Merryn M Pant Dikshya D Shakya Mila M Liu Xinxue X Colin-Jones Rachel R Theiss-Nyland Katherine K Smith Nicola N Shrestha Shrijana S Basnyat Buddha B Pollard Andrew J AJ Pitzer Virginia E VE

PLoS neglected tropical diseases 20200116 1

<h4>Background</h4>In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence.<h4>Methods</h4>We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower ri ...[more]

PMID: 31945052

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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:BackgroundThe scarcity of country data (e.g. a cancer registry) for the burden of cervical cancer (CC) in low-income countries (LCIs) such as Swaziland remains a huge challenge. Such data are critical to inform local decision-making regarding resource allocation [1]. We aimed to estimate likely cervical cancer incidence in Swaziland using three different methodologies (triangulation), to help better inform local policy guidance regarding likely higher "true" burden and increased resource allocation required for treatment, cervical cancer screening and HPV vaccine implementation.MethodsThree methods were applied to estimate CC incidence, namely: 1) application of age-specific CC incidence rates for Southern African region from GLOBOCAN 2012 extrapolated to the 2014 Swaziland female population; 2) a linear regression based model with transformed age-standardised CC incidence against hr-HPV (with and without HIV as a covariate) prevalence among women with normal cervical cytology; and 3) a mathematical model, using a natural history approach based on parameter estimates from various available literature and local survey estimates. We then triangulated estimates and uncertainty from the three models to estimate the most likely CC incidence rate for Swaziland in 2015.ResultsThe projected incidence estimates for models 1-3 were 69.4 (95% CI: 66.7-72.1), 62.6 per 100,000 (95%CI: 53.7-71.8) and 44.6 per 100,000 (41.5 to 52.1) respectively. Model 2 with HIV prevalence as covariate estimated a higher CC incidence rate estimate of 101.1 per 100,000 (95%CI: 90.3-112.2). The triangulated ('averaged') age-standardized CC incidence based across the 3 models for 2015 was estimated at 69.4 per 100,000 (95% CI: 63.0-77.1) in Swaziland.ConclusionIt is widely accepted that cancer incidence (and in this case CC) is underestimated in settings with poor and lacking registry data. Our findings suggest that the projected burden of CC is higher than that suggested from other sources. Local health policy decisions and decision-makers need to re-assess resource allocation to prevent and treat CC effectively, which is likely to persist given the very high burden of hr-HPV within the country.

Dataset Information

Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates.

Publications

Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates.

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