Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Derivation and Internal Validation of a Novel Risk Assessment Tool to Identify Infants and Young Children at Risk for Post-Discharge Mortality in Dar es Salaam, Tanzania and Monrovia, Liberia.

OBJECTIVE: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa. STUDY DESIGN: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019 to 2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P<0.20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions. RESULTS: There were 1,933 young children enrolled in the study. The median (interquartile range) age was 11 (4, 23) months and 58.7% were male. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (adjusted odds ratio [aOR] 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration. CONCLUSIONS: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children.

Predictors of severity and prolonged hospital stay of viral acute respiratory infections (ARI) among children under five years in Burkina Faso, 2016-2019.

BACKGROUND: Viruses are the leading etiology of acute respiratory infections (ARI) in children. However, there is limited knowledge on drivers of severe acute respiratory infection (SARI) cases involving viruses. We aimed to identify factors associated with severity and prolonged hospitalization of viral SARI among children < 5 years in Burkina Faso. METHODS: Data were collected from four SARI sentinel surveillance sites during October 2016 through April 2019. A SARI case was a child < 5 years with an acute respiratory infection with history of fever or measured fever ≥ 38 °C and cough with onset within the last ten days, requiring hospitalization. Very severe ARI cases required intensive care or had at least one danger sign. Oropharyngeal/nasopharyngeal specimens were collected and analyzed by multiplex real-time reverse-transcription polymerase chain reaction (rRT-PCR) using FTD-33 Kit. For this analysis, we included only SARI cases with rRT-PCR positive test results for at least one respiratory virus. We used simple and multilevel logistic regression models to assess factors associated with very severe viral ARI and viral SARI with prolonged hospitalization. RESULTS: Overall, 1159 viral SARI cases were included in the analysis after excluding exclusively bacterial SARI cases (n = 273)very severe viral ARI cases were common among children living in urban areas (AdjOR = 1.3; 95% CI: 1.1-1.6), those < 3 months old (AdjOR = 1.5; 95% CI: 1.1-2.3), and those coinfected with Klebsiella pneumoniae (AdjOR = 1.9; 95% CI: 1.2-2.2). Malnutrition (AdjOR = 2.2; 95% CI: 1.1-4.2), hospitalization during the rainy season (AdjOR = 1.71; 95% CI: 1.2-2.5), and infection with human CoronavirusOC43 (AdjOR = 3; 95% CI: 1.2-8) were significantly associated with prolonged length of hospital stay (> 7 days). CONCLUSION: Younger age, malnutrition, codetection of Klebsiella pneumoniae, and illness during the rainy season were associated with very severe cases and prolonged hospitalization of SARI involving viruses in children under five years. These findings emphasize the need for preventive actions targeting these factors in young children.

Household hardships and responses to COVID-19 pandemic-related shocks in Eastern Ethiopia.

BACKGROUND: COVID-19 resulted in enormous disruption to life around the world. To quell disease spread, governments implemented lockdowns that likely created hardships for households. To improve knowledge of consequences, we examine how the pandemic period was associated with household hardships and assess factors associated with these hardships. METHODS: We conducted a cross-sectional study using quasi-Poisson regression to examine factors associated with household hardships. Data were collected between August and September of 2021 from a random sample of 880 households living within a Health and Demographic Surveillance System (HDSS) located in the Harari Region and the District of Kersa, both in Eastern Ethiopia. RESULTS: Having a head of household with no education, residing in a rural area, larger household size, lower income and/or wealth, and community responses to COVID-19, including lockdowns and travel restrictions, were independently associated with experiencing household hardships. CONCLUSIONS: Our results identify characteristics of groups at-risk for household hardships during the pandemic; these findings may inform efforts to mitigate the consequences of COVID-19 and future disease outbreaks.

Triumph of Pneumococcal Conjugate Vaccines: Overcoming a Common Foe.

Pneumococcal conjugate vaccine (PCV) has reduced the burden of pneumococcal disease by the near elimination of vaccine serotypes from countries giving a booster dose at >9 months of life. Herd protection, induced by interruption of pneumococcal vaccine type transmission has protected children too young to be immunized, children and adults with underlying risk conditions for invasive pneumococcal disease, and the elderly. PCV has rolled out in most poor countries, but millions of children remain un-immunized especially in middle income countries because of cost constraints. These are being met by considering fewer doses to maintain herd protection, and support for more affordable vaccine from developing country manufacturers. While 3rd generation PCV's with potential inclusion of 20+ serotypes are close to market in adults, it will be their introduction into childhood immunization and herd protection that is most likely to maximize the public health benefits of these vaccines.

High Prevalence of Vaccine-Type Infections Among Children with Pneumococcal Pneumonia and Effusion After 13-Valent Pneumococcal Conjugate Vaccine Introduction in the Dominican Republic.

BACKGROUND: In 2013, the Dominican Republic introduced 13-valent pneumococcal conjugate vaccine (PCV13) using a 3-dose schedule (at 2, 4 and 12 months of age). We evaluated the impact of PCV13 on serotypes causing pneumococcal pneumonia with pleural effusion. METHODS: Surveillance data after PCV13 introduction (July 2014 to June 2016) were compared with data before PCV13 introduction (July 2009 to June 2011). Cases were defined as radiologic evidence of pneumonia with pleural effusion in a child aged <15 years. Pneumococcus was detected in pleural fluid by either culture or polymerase chain reaction, and serotyping was performed. The Ministry of Health's PCV13 uptake data for 2014-2016 were obtained. RESULTS: The prevalence of pneumococcus among cases was similar before and after PCV13 introduction (56.4% and 52.8%, respectively). The proportion of pneumococcal cases caused by vaccine serotypes was 86% for children <2 years old both before and PCV13 introduction. Compared with before PCV13, serotype 14 accounted for a smaller (28% vs 13%, respectively; P = .02) and serotype 1 for a larger (23% vs 37%; P = .09) proportion of pneumococcal cases after PCV13 introduction. National uptake for the first, second, and third PCV13 doses was 94%, 81%, and 28%, respectively, in 2014 and 75%, 61%, and 26% in 2015. DISCUSSION: While the decrease in pneumococcal pneumonia with pleural effusion caused by serotype 14 may reflect an early effect of PCV13 implementation, other vaccine serotypes, including serotype 1, are not well controlled. Better PCV13 coverage for all 3 doses is needed.

Pneumococcal Carriage in Burkina Faso After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results From 2 Cross-sectional Population-Based Surveys.

BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

Deaths Attributed to Respiratory Syncytial Virus in Young Children in High-Mortality Rate Settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS).

BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings.

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization.

BACKGROUND: Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children. METHODS: Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR. RESULTS: Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum ß-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75). CONCLUSION: Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.

Early Impact of 13-Valent Pneumococcal Conjugate Vaccine Use on Invasive Pneumococcal Disease Among Adults With and Without Underlying Medical Conditions-United States.

BACKGROUND: The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. METHODS: Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013-2014 and 2007-2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. RESULTS: IPD incidence declined among all adults. Among adults 19-64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], -68% to -43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, -62% to -52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, -78% to -70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, -76% to -60%) in those with immunocompromising conditions, 68% (95% CI, -72% to -63%) in those with CMCs, and 71% (95% CI, -77% to -64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. CONCLUSIONS: IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

Impact of 10-Valent Pneumococcal Conjugate Vaccine Introduction on Pneumococcal Carriage and Antibiotic Susceptibility Patterns Among Children Aged <5 Years and Adults With Human Immunodeficiency Virus Infection: Kenya, 2009-2013.

BACKGROUND: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination.

Identification of Streptococcus suis Meningitis by Direct Triplex Real-Time PCR, Burkina Faso.

Meningitis confirmation in Burkina Faso uses PCR for detecting Streptococcus pneumoniae, Neisseria meningitidis, or Hemophilus influenzae. We identified 38 cases of meningitis among 590 that were PCR-positive for 3 nonpneumococcal streptococcal pathogens, including 21 cases of Streptococcus suis. Among the country's 13 regions, 10 had S. suis-positive cases.

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

Dried blood spots for Streptococcus pneumoniae and Haemophilus influenzae detection and serotyping among children < 5 years old in rural Mozambique.

BACKGROUND: Dried blood spots (DBS) have been proposed as potentially tool for detecting invasive bacterial diseases. METHODS: We evaluated the use of DBS for S. pneumoniae and H. influenzae detection among children in Mozambique. Blood for DBS and nasopharyngeal (NP) swabs were collected from children with pneumonia and healthy aged < 5 years. Bacterial detection and serotyping were performed by quantitative PCR (qPCR) (NP and DBS; lytA gene for pneumococcus and hpd for H. influenzae) and culture (NP). Combined detection rates were compared between children with pneumonia and healthy. RESULTS: Of 325 children enrolled, 205 had pneumonia and 120 were healthy. Pneumococci were detected in DBS from 20.5 and 64.2% of children with pneumonia and healthy, respectively; NP specimens were positive for pneumococcus in 80.0 and 80.8%, respectively. H. influenzae was detected in DBS from 22.9% of children with pneumonia and 59.2% of healthy; 81.4 and 81.5% of NP specimens were positive for H. influenzae, respectively. CONCLUSION: DBS detected pneumococcal and H. influenzae DNA in children with pneumonia and healthy. Healthy children were often DBS positive for both bacteria, suggesting that qPCR of DBS specimens does not differentiate disease from colonization and is therefore not a useful diagnostic tool for children.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis, Burkina Faso, 2016-2017.

BACKGROUND: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis. METHODS: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13's introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories. RESULTS: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (≥15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes. CONCLUSIONS: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13's impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting.

Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratories.

Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30-45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories.

Indirect Effects of 10-Valent Pneumococcal Conjugate Vaccine Against Adult Pneumococcal Pneumonia in Rural Western Kenya.

BACKGROUND: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011. METHODS: From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0°C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence. RESULTS: Pre-PCV (2008-2010) crude and adjusted ARI incidences were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0-1.3). In each post-PCV year (2012-2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) of 0.53 (95% CI: 0.31-0.61) in 2012 and 0.13 (95% CI: 0.09-0.17) in 2016. Similar declines were observed in HIV-infected (IRR: 0.13; 95% CI: 0.08-0.22) and HIV-uninfected (IRR: 0.10; 95% CI: 0.05-0.20) adults. CONCLUSIONS: Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.

Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays.

Background: Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods: We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens. Results: Among 1736 patients with SSUAD and ≥1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of pneumonia cases caused by serotypes exclusively covered by PCV13 was not significantly different between the first and second July-June study periods (6.4% vs 4.0%). Conclusions: Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.

Effectiveness of 13-pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease in children in the Dominican Republic.

BACKGROUND: Limited data are available on the effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in resource-poor settings and PCV naïve populations. The Dominican Republic introduced PCV13 in September 2013 using a 2 + 1 schedule (2, 4, and 12 months) without a catch-up campaign. We evaluated PCV13 effectiveness against vaccine-type (VT) invasive pneumococcal disease (IPD) among children in the Dominican Republic. METHODS: We conducted a matched case-control study. A case-patient was defined as VT-IPD identified by culture or polymerase chain reaction (PCR) from a normally sterile-site in a hospitalized child who was age-eligible to have received ≥1 PCV13 dose. Four age- and neighborhood-matched controls were enrolled for each case-patient. We collected demographic, vaccination history, and risk factor data. Conditional logistic regression was performed. Vaccine effectiveness was calculated as (1- adjusted matched odds ratio for vaccination) X 100%. RESULTS: We enrolled 39 case-patients and 149 matched-controls. Most case-patients had pneumonia with pleural effusion (64%), followed by meningitis (28%) and septicemia (13%). The most common pneumococcal serotypes identified included 14 (18%), 3 (13%), 19A (10%), and 1 (8%). Fewer case-patients had ≥1 PCV13 dose as compared to controls (61.5% vs. 80.0%; p = 0.006). Adjusting for malnutrition and socioeconomic status, VE of ≥1 PCV13 dose compared to no doses was 67.2% (95% CI: 2.3% to 90.0%). Only 44% of controls were up-to-date for PCV13, suggesting low vaccine coverage in the population. CONCLUSIONS: We found that PCV13 provided individual protection against VT-IPD in this resource-poor setting with a PCV-naïve population, despite low PCV13 coverage. Expanding vaccination coverage might increase PCV13 impact.