Childhood Pneumonia Mortality Research Articles

Reductions in Childhood Pneumonia Mortality After Vaccination in the United States.

We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States. We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs). Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0-1-month-old children was 2.55 per 100,00 pop., whereas for 2-11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0-59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4-21) and 19% (95% CI: 0-33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4-35) for all-cause pneumonia mortality and 22% (95% CI: -19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6-11-month-old infants. The universal introduction of PCV7, and later PCV13, for children 0-59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.

Bacterial etiology of pneumonia in children up to 2 months of age: a systematic review

Background: Following the widespread introduction of childhood pneumococcal conjugate vaccines (PCVs), a significant impact on pneumonia mortality in children under five years of age has been reported. It is still unknown whether PCVs are expected to reduce pneumonia burden in younger children, particularly ≤2 months of age, as current evidence on the role of S. pneumoniae in pneumonia etiology in this age group is scarce. We aimed to summarize the evidence of bacterial etiology of pneumonia in children ≤2 months of age. Methods: We conducted a systematic review considering studies evaluating a variety of syndromes associated with pneumonia, and reporting on laboratory confirmed etiologies, considering any diagnostic method and a variety of clinical specimens. We searched Medline/PubMed, Embase, WoS, Central and Index Medicus Global published in any language till April 30th, 2021. We included studies addressing the outcomes of interest in children ≤2 months of age and reporting on clinical trials, observational studies, and case series with at least 10 events. Screening of citations and data extraction were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analyses of the various etiologic agents by syndrome are reported. Results: We identified 3,744 citations, of which 22 publications reporting on 13 studies were included. Study methods varied significantly. Nonetheless, gram positive organisms, in particular S. pneumoniae, were identified as important etiologic agents of pneumonia in children ≤2 months of age. Viral etiologies, in particular Respiratory Syncytial Virus, Rhinovirus, and Influenza were also identified. Conclusions: This review provides the most comprehensive analysis to date of the etiologies of pneumonia in children ≤2 months of age, suggesting that PCV impact is expected to occur in this age group. These results also have major implications for diagnosis and treatment of pneumonia in this age group.

The indirect effects of COVID-19 upon global childhood pneumonia

ObjectivesThe relative scarcity of paediatric COVID-19 disease infers protection from its direct harms. We aim to highlight the potentially severe indirect effects of COVID-19 upon global childhood pneumonia. Study designThis is a discussion piece written from the authors’ perspective. MethodsWe use the social determinants of health to describe the indirect impact of COVID-19 upon global childhood pneumonia. ResultsThe social determinants of health are a range of social, economic, and environmental factors used to explore and explain global health differences and inequalities. Global childhood pneumonia is a significant public health problem with clear linkage to the social determinants of health. COVID-19 is a significant threat to the health and wellbeing of children around the world through its potentially severe effects on all strata of the social determinants of health. ConclusionsThe COVID-19 pandemic could undermine years of progress in reducing both global childhood pneumonia incidence and mortality, and most significantly affect vulnerable children living in poverty.

Oxygen systems strengthening as an intervention to prevent childhood deaths due to pneumonia in low-resource settings: systematic review, meta-analysis and cost-effectiveness

ObjectivesIncreasing access to oxygen services may improve outcomes among children with pneumonia living in low-resource settings. We conducted a systematic review to estimate the impact and cost-effectiveness of strengthening oxygen...

Impact of pneumococcal conjugate vaccine uptake on childhood pneumonia mortality across income levels in Brazil, Colombia, and Peru

Background: Pneumococcal conjugate vaccines (PCVs) have prevented deaths due to pneumonia among children. The effect may differ between higher- and lower-income populations due to various factors, such as differences in the distribution of pneumococcal serotypes, healthcare access, and PCV uptake. This study aims to evaluate an association between increasing PCV coverage and population-level declines in death due to pneumonia and its variation by socioeconomic status of subnational regions. Methods: We analyzed municipality-level mortality data from 2005 and 2015 for children aged 2-23 months in Brazil, Colombia, and Peru. We fit Poisson regression models to estimate the relationship between changes in PCV uptake and deaths due to all-cause pneumonia among subnational regions with different income levels. We controlled for changes unrelated to PCV by using data on non-respiratory deaths over time. Results: Uptake of the third dose of PCV varied across subnational regions and was higher in high-income regions. Higher uptake of PCV was associated with larger declines in pneumonia mortality. This association did not differ by income level of the region in Brazil and Colombia. In Peru, low-income regions observed larger declines in pneumonia deaths, but there was large uncertainty in the difference between the low- and high-income regions. We estimated that, with 90% coverage, there would be 4-38% declines in all-cause pneumonia mortality across income levels and countries. Conclusions: Regions with higher PCV coverage experienced larger declines in pneumonia deaths, regardless of the income level. Having more reliable data on mortality records and vaccine uptake would improve the reliability of vaccine impact estimates.

Impact of pneumococcal conjugate vaccine on pneumonia hospitalization and mortality in children and elderly in Ecuador: Time series analyses

BackgroundPneumococcal conjugate vaccines (PCV) reduce the burden of invasive pneumococcal disease and pneumonia hospitalizations. However, there is limited evidence of the effect of PCVs on pneumonia mortality in children. It is anticipated that indirect effects resulting from PCV use among children might further reduce the remaining burden of adult pneumococcal disease caused by pneumococcal serotypes contained in PCV. Whether this will result in reduced pneumonia mortality in children and adults is still not known. MethodsWe investigated the impact of PCV on pneumonia hospitalization and mortality in in Ecuador, where PCV was introduced in 2010, considering national data from secondary data sources from 2005 to 2015. Time series analysis using regression models were used to evaluate the decline in the number of all-cause pneumonia hospitalizations and deaths in the period post-PCV introduction. The target populations were children under 5 years and adults aged 50 years and over. Outcomes of interest were hospitalizations and mortality in which the main cause of hospital admission and death, respectively, were coded as ICD10 codes J12-18 (pneumonia). Three different models were fitted. ResultsWe demonstrate a sizeable impact of PCV in pneumonia hospitalization in children < 1 year (27% reduction, 95%CI 12–42%), and < 5 years of age (33% reduction, 95%CI 11–43%). The estimated impact of PCV in pneumonia mortality was a reduction of 14% in < 1 year (95%CI 0–33%), 10% in < 5 years (95%CI 0–25%), and 22% (95%CI 7–34%) in adults aged 50–64 years. Little evidence of a change was detected in elderly ≥ 65 years. ConclusionThis study is the first to report on the impact of PCV in pneumonia morbidity and mortality in children and older adults, being relevant to policy makers and global donors. Findings were consistent when using different models. Additional studies on the indirect effect of PCV in older adults are needed.

Impact of pneumococcal conjugate vaccine uptake on childhood pneumonia mortality across income levels in Brazil, Colombia, and Peru.

Background: Pneumococcal conjugate vaccines (PCVs) have prevented deaths due to pneumonia among children. The effect may differ between higher- and lower-income populations due to various factors, such as differences in the distribution of pneumococcal serotypes, healthcare access, and PCV uptake. This study aims to evaluate an association between increasing PCV coverage and population-level declines in death due to pneumonia and its variation by socioeconomic status of subnational regions. Methods: We analyzed municipality-level mortality data from 2005 and 2015 for children aged 2-23 months in Brazil, Colombia, and Peru. We fit Poisson regression models to estimate the relationship between changes in PCV uptake and deaths due to all-cause pneumonia among subnational regions with different income levels. We controlled for changes unrelated to PCV by using data on non-respiratory deaths over time. Results: Uptake of the third dose of PCV varied across subnational regions and was higher in high-income regions. Higher uptake of PCV was associated with larger declines in pneumonia mortality. This association did not differ by income level of the region in Brazil and Colombia. In Peru, low-income regions observed larger declines in pneumonia deaths, but there was large uncertainty in the difference between the low- and high-income regions. We estimated that, with 90% coverage, there would be 4-38% declines in all-cause pneumonia mortality across income levels and countries. Conclusions: Regions with higher PCV coverage experienced larger declines in pneumonia deaths, regardless of the income level. Having more reliable data on mortality records and vaccine uptake would improve the reliability of vaccine impact estimates.

Digital auscultation in PERCH: Associations with chest radiography and pneumonia mortality in children

BackgroundWhether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low‐income and middle‐income countries is unknown. We sought to address these knowledge gaps.MethodsWe enrolled 1 to 59monthold children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes. Recordings were processed and classified into binary categories positive or negative for adventitial lung sounds. Listening and reading panels classified recordings and radiographs. Recording classification associations with chest radiographs with World Health Organization (WHO)‐defined primary endpoint pneumonia (radiographic pneumonia) or mortality were evaluated. We also examined case fatality among risk strata.ResultsAmong children without WHO danger signs, wheezing (without crackles) had a lower adjusted odds ratio (aOR) for radiographic pneumonia (0.35, 95% confidence interval (CI): 0.15, 0.82), compared to children with normal recordings. Neither crackle only (no wheeze) (aOR: 2.13, 95% CI: 0.91, 4.96) or any wheeze (with or without crackle) (aOR: 0.63, 95% CI: 0.34, 1.15) were associated with radiographic pneumonia. Among children with WHO danger signs no lung recording classification was independently associated with radiographic pneumonia, although trends toward greater odds of radiographic pneumonia were observed among children classified with crackle only (no wheeze) or any wheeze (with or without crackle). Among children without WHO danger signs, those with recorded wheezing had a lower case fatality than those without wheezing (3.8% vs. 9.1%, p = .03).ConclusionsAmong lower risk children without WHO danger signs digitally recorded wheezing is associated with a lower odds for radiographic pneumonia and with lower mortality. Although further research is needed, these data indicate that with further development digital auscultation may eventually contribute to child pneumonia care.

Relationship between Predisposition, Hypoxia and Chest Radiographs Abnormality on Mortality of 2-59 Months Old Children with Pneumonia

Background: Pneumonia in children was significant cause of death in world.(1, 2) About 150 million cases of pneumonia in under 5 years old children, 20 million cases include severe pneumonia with a high mortality rate.(3, 4) Based on the 2012 Indonesian Demographic Health Survey, infant mortality rate due to pneumonia was 40/1000 live births.(5) But there are no data describing factors that contribute to pneumonia mortality in Indonesian children. Objective: To analyze relationship between predisposition, hypoxia and chest radiographs on mortality of 2-59 months old children with pneumonia. Methods: Retrospective case control study by taking secondary data through medical records for the period 2016-2018 in the Dr. Soetomo Hospital Results: one hundred and four patients were enrolled, 52 patients were died (case group) and 52 patients were cured (control group). Bivariate analysis show that factor of pneumonia mortality in children were age under 12 months, non-exclusive breastfeeding, overcrowding, incomplete immunization, malnutrition, comorbidities, hypoxia and extensive infiltrates, consolidation, pleural effusions on chest radiographs. Logistic regression analysis show factors that most influenced the pneumonia mortality in children were age under 12 months, malnutrition, overcrowding and extensive infiltrates, consolidation, pleural effusion on plain chest radiographs Conclusion: Age under 12 months, malnutrition, overcrowding and extensive infiltrate, consolidation, pleural effusion on chest radiographs were the factors that most influence the pneumonia mortality.

Management of childhood pneumonia in Nigeria.

Management of childhood pneumonia in Nigeria.

Seasonal variation and etiologic inferences of childhood pneumonia and diarrhea mortality in India.

Control of pneumonia and diarrhea mortality in India requires understanding of their etiologies. We combined time series analysis of seasonality, climate region, and clinical syndromes from 243,000 verbal autopsies in the nationally representative Million Death Study. Pneumonia mortality at 1 month-14 years was greatest in January (Rate ratio (RR) 1.66, 99% CI 1.51-1.82; versus the April minimum). Higher RRs at 1-11 months suggested respiratory syncytial virus (RSV) etiology. India's humid subtropical region experienced a unique summer pneumonia mortality. Diarrhea mortality peaked in July (RR 1.66, 1.48-1.85) and January (RR 1.37, 1.23-1.48), while deaths with fever and bloody diarrhea (indicating enteroinvasive bacterial etiology) showed little seasonality. Combining mortality at ages 1-59 months with prevalence surveys, we estimate 40,600 pneumonia deaths from Streptococcus pneumoniae, 20,700 from RSV, 12,600 from influenza, and 7200 from Haemophilus influenzae type b and 24,700 diarrheal deaths from rotavirus occurred in 2015. Careful mortality studies can elucidate etiologies and inform vaccine introduction.

Effect of pneumococcal conjugate vaccine introduction on childhood pneumonia mortality in Brazil: a retrospective observational study.

SummaryBackgroundUnderstanding the real-world effect of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is crucial because of the expectation that increased PCV use will substantially reduce the burden of pneumonia deaths in children younger than 5 years. However, few post-vaccine introduction studies have estimated the benefits of PCV use on childhood mortality and results have been inconsistent. Therefore, we set out to assess the effect of introduction of ten-valent pneumococcal conjugate vaccine (PCV10) on pneumonia mortality in children in Brazil.MethodsIn this retrospective observational study, we used publicly available mortality data of children aged 3–59 months in Brazil. We separated data by age group (3–11 months, 3–23 months, and 3–59 months) and stratified data by three different socioeconomic factors of Brazilian municipalities (in 2010): Human Development Index, proportion of children living in extreme poverty, and proportion of mothers with no primary education. We first examined long-term trends in childhood pneumonia mortality in Brazil (from 1980 to 2014). We then assessed the effect of PCV10—introduced in Brazil in 2010—both nationally and in municipalities stratified by socioeconomic status, with a synthetic control approach as our primary analytical method.FindingsBetween 1980 and 2010, a period during which Brazil's Human Development Index rose substantially, national pneumonia mortality in children younger than 5 years decreased from about 150 to 15 deaths per 100 000 children younger than 5 years. Despite rapid uptake of PCV10 after its introduction in 2010, we observed a further vaccine-associated decline of about 10% in national childhood pneumonia mortality with our primary analytical method, with a high degree of uncertainty in the estimates. We observed larger reductions in municipal childhood pneumonia mortality in all three age groups (3–11 months, 3–23 months, and 3–59 months) in municipalities with a high percentage of extreme childhood poverty and mothers with no primary education, with the largest decrease observed in children aged 3–23 months in municipalities with low maternal education (24%, 95% credible interval 7–35).InterpretationThe large reduction observed from 1980 to 2010 in national pneumonia mortality in children younger than 5 years underscores that improvements in nutrition, hygiene, education, and health care have an important role in reducing pneumonia mortality. Although the PCV-associated reduction in childhood pneumonia mortality at the national level was modest, we found that PCV led to larger reductions in low-income municipalities. Similarly, large benefits might occur when PCVs are introduced in other low-income settings.FundingBill & Melinda Gates Foundation and National Institute of Allergy and Infectious Diseases.

Improving oxygen therapy for children and neonates in secondary hospitals in Nigeria: study protocol for a stepped-wedge cluster randomised trial

BackgroundOxygen is a life-saving, essential medicine that is important for the treatment of many common childhood conditions. Improved oxygen systems can reduce childhood pneumonia mortality substantially. However, providing oxygen to children is challenging, especially in small hospitals with weak infrastructure and low human resource capacity.Methods/designThis trial will evaluate the implementation of improved oxygen systems at secondary-level hospitals in southwest Nigeria. The improved oxygen system includes: a standardised equipment package; training of clinical and technical staff; infrastructure support (including improved power supply); and quality improvement activities such as supportive supervision. Phase 1 will involve the introduction of pulse oximetry alone; phase 2 will involve the introduction of the full, improved oxygen system package. We have based the intervention design on a theory-based analysis of previous oxygen projects, and used quality improvement principles, evidence-based teaching methods, and behaviour-change strategies.We are using a stepped-wedge cluster randomised design with participating hospitals randomised to receive an improved oxygen system at 4-month steps (three hospitals per step). Our mixed-methods evaluation will evaluate effectiveness, impact, sustainability, process and fidelity. Our primary outcome measures are childhood pneumonia case fatality rate and inpatient neonatal mortality rate. Secondary outcome measures include a range of clinical, quality of care, technical, and health systems outcomes. The planned study duration is from 2015 to 2018.DiscussionOur study will provide quality evidence on the effectiveness of improved oxygen systems, and how to better implement and scale-up oxygen systems in resource-limited settings. Our results should have important implications for policy-makers, hospital administrators, and child health organisations in Africa and globally.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12617000341325. Retrospectively registered on 6 March 2017.

Pneumonia Mortality in Children Aged

Pneumonia is now the second leading cause of death for children aged <5 years worldwide. However, analyses of the long-term evolution of under-5 mortality from pneumonia are still scarce in the literature. We aimed to explore long-term trends of under-5 mortality from pneumonia in 56 countries from 1960 to 2012. Data on under-5 mortality from pneumonia were extracted from the World Health Organization mortality database. Long-term trends were assessed for 56 countries and for 4 national income transition groups. We also used joinpoint regression analysis to detect distinct period segments of long-term trends and estimate the annual percent of changes of each period segment. The average mortality rate from pneumonia for children aged 0-4 years in 56 countries declined from 163.0 per 100000 children (95% confidence interval [CI], 119.4 to 212.8) in 1960 to 9.9 per 100000 children (95% CI, 6.4 to 13.4) in 2012, with an average annual percent of change of -5.6% (95% CI, -7.2% to -3.9%). The temporal trends of childhood mortality were different between national income transition groups. Our findings suggest a striking overall downward trend in under-5 mortality from pneumonia between 1960 and 2012. However, the rate and absolute terms of decline differ by national income transition group. These variable patterns between national income transition groups may inform further intervention setting and priority setting.

Estimation of distribution of childhood diarrhoea, measles, and pneumonia morbidity and mortality by socio-economic group in low-income and middle-income countries

Abstract Background Vaccines are one of the most successful interventions in improving population health in low-income and middle-income countries (LMICs). In addition to the direct improvements in health outcomes, we are interested in their distributional effects—that is, whether vaccines promote or reduce health equity across socioeconomic groups. Empirical data on incidence and mortality of vaccine-preventable diseases across socioeconomic groups is not available. Therefore, we developed a method to estimate the distribution of childhood diseases and deaths across income groups and the benefits of three vaccines—for diarrhoea, measles, and pneumonia—in 41 LMICs. Methods For every country and disease (diarrhoea, measles, pneumonia), we estimated the distribution of cases and deaths that would occur in each income quintile had there been no immunisation or treatment programme, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we assessed the effect of three vaccines (first dose of measles vaccine, pneumococcal conjugate vaccine, and rotavirus vaccine) under five scenarios based on sets of quintile-specific immunisation coverage and uptake of disease treatment. Findings Because the prevalence of risk factors is higher in the poorest two quintiles than in the rest of the population, more disease cases and deaths would occur in the poorest two quintiles for all three diseases when vaccines or treatment are unavailable. However, we noted that current immunisation coverage and treatment utilisation rates have resulted in greater inequity in the distribution of cases and deaths. Even if in absolute terms the poorest quintiles benefit more from vaccines, the wealthier two quintiles sees a higher percentage decrease in cases and deaths. Thus, in terms of overall distribution of remaining cases and deaths with vaccine coverage, the poorest quintiles would see a higher comparative burden of disease than they would without vaccine coverage. Country-specific context, including how the baseline risks, immunisation coverage, and treatment utilisation are currently distributed across quintiles, affects how different policies translate to improvements in the distribution of cases and deaths. Interpretation Our analysis highlights several factors, including risk and prognostic factors, and vaccine and treatment coverage that would substantially contribute to the unequal distribution of childhood diseases, and we found that merely ensuring equal access to vaccines will not reduce the health outcomes gap between income quintiles. Such information can inform policies and planning of programmes that aim to improve equitable delivery of healthcare services. Funding Bill & Melinda Gates Foundation.

Reduction of childhood pneumonia mortality in the Sustainable Development era

Reduction of childhood pneumonia mortality in the Sustainable Development era

Evaluating the impact of pulse oximetry on childhood pneumonia mortality in resource-poor settings.

It is estimated that pneumonia is responsible for 15% of childhood deaths worldwide. Recent research has shown that hypoxia and malnutrition are strong predictors of mortality in children hospitalized for pneumonia. It is estimated that 15% of children under 5 who are hospitalized for pneumonia have hypoxaemia and that around 1.5 million children with severe pneumonia require oxygen treatment each year. We developed a deterministic compartmental model that links the care pathway to disease progression to assess the impact of introducing pulse oximetry as a prognostic tool to distinguish severe from non-severe pneumonia in under-5 year olds across 15 countries with the highest burden worldwide. We estimate that, assuming access to supplemental oxygen, pulse oximetry has the potential to avert up to 148,000 deaths if implemented across the 15 countries. By contrast, integrated management of childhood illness alone has a relatively small impact on mortality owing to its low sensitivity. Pulse oximetry can significantly increase the incidence of correctly treated severe cases as well as reduce the incidence of incorrect treatment with antibiotics. We also found that the combination of pulse oximetry with integrated management of childhood illness is highly cost-effective, with median estimates ranging from US$2.97 to $52.92 per disability-adjusted life year averted in the 15 countries analysed. This combination of substantial burden reduction and favourable cost-effectiveness makes pulse oximetry a promising candidate for improving the prognosis for children with pneumonia in resource-poor settings.

MPneumonia: Development of an Innovative mHealth Application for Diagnosing and Treating Childhood Pneumonia and Other Childhood Illnesses in Low-Resource Settings.

Pneumonia is the leading infectious cause of death in children worldwide. Each year, pneumonia kills an estimated 935,000 children under five years of age, with most of these deaths occurring in developing countries. The current approach for pneumonia diagnosis in low-resource settings—using the World Health Organization Integrated Management of Childhood Illness (IMCI) paper-based protocols and relying on a health care provider’s ability to manually count respiratory rate—has proven inadequate. Furthermore, hypoxemia—a diagnostic indicator of the presence and severity of pneumonia often associated with an increased risk of death—is not assessed because pulse oximetry is frequently not available in low-resource settings. In an effort to address childhood pneumonia mortality and improve frontline health care providers’ ability to diagnose, classify, and manage pneumonia and other childhood illnesses, PATH collaborated with the University of Washington to develop “mPneumonia,” an innovative mobile health application using an Android tablet. mPneumonia integrates a digital version of the IMCI algorithm with a software-based breath counter and a pediatric pulse oximeter. We conducted a design-stage usability field test of mPneumonia in Ghana, with the goal of creating a user-friendly diagnostic and management tool for childhood pneumonia and other childhood illnesses that would improve diagnostic accuracy and facilitate adherence by health care providers to established guidelines in low-resource settings. The results of the field test provided valuable information for understanding the usability and acceptability of mPneumonia among health care providers, and identifying approaches to iterate and improve. This critical feedback helped ascertain the common failure modes related to the user interface design, navigation, and accessibility of mPneumonia and the modifications required to improve user experience and create a tool aimed at decreasing mortality from pneumonia and other childhood illnesses in low-resource settings.

Changes in Childhood Pneumonia and Infant Mortality Rates Following Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Nicaragua

In 2010, Nicaragua became the first developing nation to add 13-valent pneumococcal conjugate vaccine (PCV-13) to its national immunization schedule, using a "3+0" dosing schedule. We assessed changes in incidence rates of health facility visits for childhood pneumonia and infant mortality after PCV-13 introduction in the Department of León, Nicaragua. We collected visit diagnoses from all 107 public health facilities in León between 2008 and 2012. We compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and infant mortality during the prevaccine (2008-2010) and vaccine (2011-2012) periods among different age groups of children using generalized estimating equations, accounting for clustering by municipality. Exposure time was estimated by official municipality population estimates. The adjusted incidence rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period was 0.67 (0.59-0.75) among infants and 0.74 (0.67-0.81) among 1-year olds. The adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75-1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted incidence rate ratio for infant mortality was 0.67 (0.57-0.80). We also observed lower rates of health facility visits for pneumonia among age groups (2- to 4-year old and 5- to 14-year old) not eligible to receive PCV-13. Within the first 2 years of a PCV-13 immunization program in Nicaragua, we observed lower rates of hospitalizations and ambulatory visits for pneumonia among children of all ages and a lower infant mortality rate. Lower rates of pneumonia among age groups not eligible to receive PCV-13 suggest an indirect effect of the vaccine.

Clinical spectrum and complications of childhood pneumonia in the era of bacterial conjugate vaccines

Pneumonia remains a leading cause of under-5 childhood mortality, particularly in low and middle-income countries. The rollout of conjugate bacterial vaccines, including Haemophilus influenzae type b conjugate vaccine (HibCV) and particularly pneumococcal conjugate vaccine (PCV), into national immunization programs recently, has been associated with dramatic decline in all-cause pneumonia hospitalization in many developed countries where PCV immunization has been implemented. Also, PCV immunization has variably been associated with changes in incidence of hospitalization due to influenza virus and RSV-associated pneumonia in some settings. There is, however, limited data from low and middle-income countries on the effectiveness of PCV against pneumonia once introduced into immunization programs. A broader diversity of serotypes associated with pneumococcal disease and higher prevalence of underlying risk factors for pneumonia such as greater prevalence of malnutrition, HIV-infection and tuberculosis may affect the impact of PCV on all-cause pneumonia morbidity and mortality in children. Furthermore, early experience from few studies in developed countries with 7-valent PCV, suggested a temporal association between PCV-7 introduction and an increase in complicated pneumonia including that due to empyema due to few serotypes not included in PCV7, but which are now included in the 10 and 13-valent PCVs formulations currently used. The global public health value of PCV will be measured by its success in reducing all-cause childhood pneumonia morbidity and mortality in low and middle-income countries. Results on the impact of PCV immunization in early-adopting low and middle incoming countries are imminent and will contribute in determining the potential of PCV in improving child health globally.