Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children.

BACKGROUND: Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance. METHODS: CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested. RESULTS: Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks. CONCLUSIONS: While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.

Enteric Fever Cases in the Two Largest Pediatric Hospitals of Bangladesh: 2013-2014.

Background: Enteric fever predominantly affects children in low- and middle-income countries. This study examines the burden of enteric fever at the 2 pediatric hospitals in Dhaka, Bangladesh and assesses their capacity for inclusion in a prospective cohort study to support enteric fever prevention and control. Methods: A descriptive study of enteric fever was conducted among children admitted in 2013-2014 to inpatient departments of Dhaka Shishu and Shishu Shashthya Foundation Hospitals, sentinel hospitals of the World Health Organization-supported Invasive Bacterial Vaccine Preventable Disease surveillance platform. Results: Of 15917 children with blood specimens received by laboratories, 2.8% (443 of 15917) were culture positive for significant bacterial growth. Sixty-three percent (279 of 443) of these isolates were confirmed as the cases of enteric fever (241 Salmonella Typhi and 38 Salmonella Paratyphi A). In addition, 1591 children had suspected enteric fever. Overall, 3.6% (1870 of 51923) were laboratory confirmed or suspected enteric fever cases (55% male, median age 2 years, 86% from Dhaka district, median hospital stay 5 days). Conclusions: The burden of enteric fever among inpatients at 2 pediatric hospitals in Dhaka, Bangladesh is substantial. Therefore, inclusion of these hospitals in a prospective cohort study will be useful for the generation of credible disease burden estimates of enteric fever in Bangladesh.

Integration of enteric fever surveillance into the WHO-coordinated Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) platform: A low cost approach to track an increasingly important disease.

BACKGROUND: Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever, caused by Salmonella Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance network but does not monitor enteric fever. We evaluated the feasibility and sustainability of integrating enteric fever surveillance into the ongoing IB-VPD platform. METHODOLOGIES: The IB-VPD surveillance system uses WHO definitions to enroll 2-59 month children hospitalized with possible pneumonia, sepsis or meningitis. We expanded this surveillance system to additionally capture suspect enteric fever cases during 2012-2016, in two WHO sentinel hospitals of Bangladesh, by adding inclusion criteria of fever ≥102°F for ≥3 days, irrespective of other manifestations. Culture-positive enteric fever cases from in-patient departments (IPD) detected in the hospital laboratories but missed by the expanded surveillance, were also enrolled to assess completion. Costs for this integration were calculated for the additional personnel and resources required. PRINCIPAL FINDINGS: In the IB-VPD surveillance, 5,185 cases were enrolled; 3% (N = 171/5185) were positive for microbiological growth, of which 55% (94/171) were culture-confirmed cases of enteric fever (85 Typhi and 9 Paratyphi A). The added inclusion criteria for enteric fever enrolled an additional 1,699 cases; 22% (358/1699) were positive, of which 85% (349/358) were enteric fever cases (305 Typhi and 44 Paratyphi A). Laboratory surveillance of in-patients of all ages enrolled 311 additional enteric fever cases (263 Typhi and 48 Paratyphi A); 9% (28/311) were 2-59 m and 91% (283/311) >59 m. Altogether, 754 (94+349+311) culture-confirmed enteric fever cases were found, of which 471 were 2-59 m. Of these 471 cases, 94% (443/471) were identified through the hospital surveillances and 6% (28/471) through laboratory results. Twenty-three percent (170/754) of all cases were children <2 years. Additional cost for the integration was USD 44,974/year, a 27% increase to the IB-VPD annual expenditure. CONCLUSION: In a setting where enteric disease is a substantial public health problem, we could integrate enteric fever surveillance into the standard IB-VPD surveillance platform at a modest cost.