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

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.