Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

BACKGROUND: The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. METHODS: We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. RESULTS: Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. CONCLUSIONS: In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children.

The Role of Molecular Testing in Pediatric Meningitis Surveillance in Southern and East African Countries, 2008-2017.

BACKGROUND: As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa's regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). METHODS: From 2008 to 2017, CSF samples collected from children <5 years old with suspected meningitis underwent routine microbiology testing in-country, and 11 680 samples were submitted for HNS PCR at the regional reference laboratory. Unconditional logistic regression, with adjustment for geographic location, was performed to identify factors associated with PCR positivity. RESULTS: The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67-8.17) and xanthochromic (1.72; 1.29-2.28), had elevated white blood cell counts (6.13; 4.71-7.99) and high protein concentrations (5.80; 4.34-7.75), and were more often HNS culture positive (32.70; 23.18-46.12). CONCLUSION: PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.

Rotavirus prevalence and genotypes among children younger than 5 years with acute diarrhea at Mulago National Referral Hospital, Kampala, Uganda.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea among children <5 years of age worldwide. To determine the prevalence of severe rotavirus infection in children admitted with acute diarrhea attending Mulago National Referral Hospital in Uganda, active sentinel surveillance was conducted from July 2006 to December 2012. METHODS: A total of 6387 children with acute diarrhea were enrolled into the public health surveillance system and of these, 5627 had stool samples collected and tested for rotavirus antigens by enzyme immunoassay ProSpecT Rotavirus kit. RESULTS: Rotavirus was detected in 1844 (32.8%) of 5627 children with acute diarrhea that had stool specimens collected, and 93% of positive cases of rotavirus gastroenteritis were between 3 and 23 months of age, with highest prevalence in children 6-11 months of age. Rotavirus infections occurred throughout the year. During the surveillance period (2006-2012), a total of 354 positive stool samples were subjected to reverse transcription polymerase chain reaction and genotyping assays. The most common genotypes detected were G1P[8] (16.1%) and G9P[8] (15.3%), followed by G2P[4] (7.6%), G9P[6] (7.1%), G8P[4] (6.5%) and G12P[6](5.6%). Mixed G or P types (17.9%) and partially typed either G or P types (10.7%) were common. CONCLUSION: Uganda would benefit by introducing rotavirus vaccine and hence reduce the hospitalization burden of managing acute diarrhea cases.

Surveillance for Streptococcus pneumoniae meningitis in children aged <5 years: implications for immunization in Uganda.

Affordable pneumococcal conjugate vaccines will soon become available to developing countries through the Global Alliance for Vaccines and Immunization. Data on Streptococcus pneumoniae meningitis epidemiology in Uganda will assist decision makers in determining the best national vaccine policy. We reviewed acute bacterial meningitis surveillance data for children aged <5 years from 3 sentinel surveillance sites in 3 Ugandan districts collected from 2001 through 2006. Serotype and antibiotic-resistance testing were performed on pneumococcal isolates collected from 2005 through 2006 from the Kampala district in the tropical central region of Uganda. Minimum pneumococcal meningitis incidence estimates were calculated for a portion of the Kampala district and all of the Gulu district, where case ascertainment was more complete. At the 3 sites, 14,388 probable acute bacterial meningitis cases were observed. The most common cause identified was S. pneumoniae (n = 331; 35% of all confirmed cases), which had an overall case fatality ratio of 19%. Yearly pneumococcal meningitis incidence was 3-20 cases per 100,000 population in Kampala versus 28-42 cases per 100,000 population in Gulu. The most commonly identified serotypes were 6A/6B (40%); 43% of isolates were serotypes that are in the available 7-valent pneumococcal conjugate vaccine and 70% are in the proposed 13-valent pneumococcal vaccine. Twenty-five isolates (83%) had intermediate resistance to penicillin but none were fully resistant. Pneumococcal meningitis is common and severe in Uganda, indicating a role for the pneumococcal conjugate vaccine.