Latent Rheumatic Heart Disease: Identifying the Children at Highest Risk of Unfavorable Outcome.

BACKGROUND: Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes. METHODS: This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect. RESULTS: Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (interquartile range, 2.0-2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic improvement, respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome. CONCLUSIONS: Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.

Noonan syndrome in diverse populations.

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

Geographical validation of the Smart Triage Model by age group.

Infectious diseases in neonates account for half of the under-five mortality in low- and middle-income countries. Data-driven algorithms such as clinical prediction models can be used to efficiently detect critically ill children in order to optimize care and reduce mortality. Thus far, only a handful of prediction models have been externally validated and are limited to neonatal in-hospital mortality. The aim of this study is to externally validate a previously derived clinical prediction model (Smart Triage) using a combined prospective baseline cohort from Uganda and Kenya with a composite endpoint of hospital admission, mortality, and readmission. We evaluated model discrimination using area under the receiver-operator curve (AUROC) and visualized calibration plots with age subsets (< 30 days, ≤ 2 months, ≤ 6 months, and < 5 years). Due to reduced performance in neonates (< 1 month), we re-estimated the intercept and coefficients and selected new thresholds to maximize sensitivity and specificity. 11595 participants under the age of five (under-5) were included in the analysis. The proportion with an endpoint ranged from 8.9% in all children under-5 (including neonates) to 26% in the neonatal subset alone. The model achieved good discrimination for children under-5 with AUROC of 0.81 (95% CI: 0.79-0.82) but poor discrimination for neonates with AUROC of 0.62 (95% CI: 0.55-0.70). Sensitivity at the low-risk thresholds (CI) were 85% (83%-87%) and 68% (58%-76%) for children under-5 and neonates, respectively. After model revision for neonates, we achieved an AUROC of 0.83 (95% CI: 0.79-0.87) with 13% and 41% as the low- and high-risk thresholds, respectively. The updated Smart Triage performs well in its predictive ability across different age groups and can be incorporated into current triage guidelines at local healthcare facilities. Additional validation of the model is indicated, especially for the neonatal model.

Family Health Days program contributions in vaccination of unreached and under-immunized children during routine vaccinations in Uganda.

BACKGROUND: We explored the contributions of the Family Health Days (FHDs) concept, which was developed by the Uganda Ministry of Health (MOH) and UNICEF as a supplementary quarterly outreach program in addition to strengthening the routine expanded program for immunization (EPI), with the aim to increase coverage, through improved access to the unimmunized or unreached and under-immunized children under 5 years. METHOD: A cross-sectional descriptive study of the Uganda MOH, Health Management Information Systems (HMIS) and UNICEF in house FHDs data was conducted covering six quarterly implementations of the program between April 2012 and December 2013. The FHDs program was implemented in 31 priority districts with low routine vaccination coverage from seven sub-regions in Uganda in a phased manner using places of worship for service delivery. RESULTS: During the six rounds of FHDs in the 31 districts, a total of 178,709 and 191,223 children received measles and Diphtheria-Pertussis-Tetanus (DPT3) vaccinations, respectively. The FHDs' contributions were 126% and 144% for measles and 103% and 122% for DPT3 in 2012 and 2013, respectively of the estimated unreached annual target populations. All implementing sub-regions after two rounds in 2012 attained over and above the desired target for DPT3 (85%) and measles (90%). The same was true in 2013 after four rounds, except for Karamoja and West Nile sub-regions, where in some districts a substantial proportion of children remained unimmunized. The administrative data for both DPT3 and measles immunization showed prominent and noticeable increase in coverage trend in FHDS regions for the months when the program was implemented. CONCLUSION: The FHDs program improved vaccination equity by reaching the unreached and hard-to-reach children and bridging the gap in immunization coverage, and fast tracking the achievement of targets recommended by the Global Vaccine Action Plan (GVAP) for measles and DPT3 (85% and 90% respectively) in implementing sub-regions and districts. The FHDs is an innovative program to supplement routine immunizations designed to reach the unreached and under immunized children.

Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010-January 2011.

BACKGROUND: In November 2010, following reports of an outbreak of a fatal, febrile, hemorrhagic illness in northern Uganda, the Uganda Ministry of Health established multisector teams to respond to the outbreak. METHODS: This was a case-series investigation in which the response teams conducted epidemiological and laboratory investigations on suspect cases. The cases identified were line-listed and a data analysis was undertaken regularly to guide the outbreak response. RESULTS: Overall, 181 cases met the yellow fever (YF) suspected case definition; there were 45 deaths (case fatality rate 24.9%). Only 13 (7.5%) of the suspected YF cases were laboratory confirmed, and molecular sequencing revealed 92% homology to the YF virus strain Couma (Ethiopia), East African genotype. Suspected YF cases had fever (100%) and unexplained bleeding (97.8%), but jaundice was rare (11.6%). The overall attack rate was 13 cases/100000 population, and the attack rate was higher for males than females and increased with age. The index clusters were linked to economic activities undertaken by males around forests. CONCLUSIONS: This was the largest YF outbreak ever reported in Uganda. The wide geographical case dispersion as well as the male and older age preponderance suggests transmission during the outbreak was largely sylvatic and related to occupational activities around forests.