Radiologically-confirmed Pneumonia Research Articles

Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study

BackgroundCommunity-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia.MethodsPCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019.DiscussionEstablishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.

Association of cytomegalovirus viremia with pneumonia severity in South African children

Background: Sub-Saharan Africa is home to a large population of HIV-infected and HIV-exposed, -uninfected (HEU) children that are at risk for severe pneumonia attributed to opportunistic infections, including human cytomegalovirus (CMV). The role of CMV in pneumonia etiopathogenesis amongst these children is disputed, however. Methods & Materials: We evaluated whole blood CMV viral load using PCR in South African children enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case–control study. Cases, 1–59 months of age hospitalized with World Health Organization-defined severe/very severe pneumonia, were matched by age and season to community controls. A composite measure of disease severity was derived for children with radiologically-confirmed pneumonia that had high-density nasopharyngeal CMV carriage and were either mechanically ventilated, hospitalised for >5 days, or died. CMV viral load on whole blood was compared between cases with severe-composite disease, all other cases and controls. Results: Cut-off densities of 3.33, 2.53 and 2.69 log10 copies/mL of CMV in whole blood, respectively, discriminated between HIV-unexposed, HEU and HIV-infected cases with radiologically-confirmed pneumonia and age-, season-matched controls. HIV-unexposed, HEU and HIV-infected children with severe composite disease were significantly younger (HIV-unexposed: 5.5 vs 6.0 vs 7.0 months; HEU: 4.0 vs 5.0 vs 9.0 months; HIV-infected: 5.5 vs 8.0 vs 9.5 months) and severely underweight (HIV-unexposed: 32.6% vs 8.7% vs 0.9%; HEU: 35.0% vs 14.4% vs 2.3%; HIV-infected: 30.4% vs 33.8% vs 12.6%) compared to all other cases and controls. CMV whole blood PCR discriminated between cases with severe-composite disease and all other cases in the HEU (adjusted odds ratio (aOR), 2.32; 95% CI, 1.09–4.91) and HIV-infected (aOR, 2.71; 95% CI, 1.15–6.39) groups. Additionally, CMV whole blood PCR discriminated between cases with severe-composite disease and controls in HIV-unexposed (aOR, 4.04; 95% CI, 1.59–10.25), HEU (aOR, 6.60; 95% CI, 1.31–33.31) and HIV-infected children (aOR, 10.29; 95% CI, 2.81–37.65). Conclusion: In African children <5 years of age hospitalized for severe community-acquired pneumonia, CMV detection in whole blood PCR discriminated between severe-composite disease and all other cases in HEU and HIV-infected patients. The test may guide choice of therapy in a select group of immunocompromised cases in whom a diagnosis of CMV pneumonia is being considered.

Hospitalization and death among patients with influenza, Guatemala, 2008\u20132012

BackgroundInfluenza is a major cause of respiratory illness resulting in 3–5 million severe cases and 291,243-645,832 deaths annually. Substantial health and financial burden may be averted by annual influenza vaccine application, especially for high risk groups.MethodsWe used an active facility-based surveillance platform for acute respiratory diseases in three hospitals in Guatemala, Central America, to estimate the incidence of laboratory-confirmed hospitalized influenza cases and identify risk factors associated with severe disease (defined as admission to the intensive care unit (ICU) or death). We enrolled patients presenting with signs and symptoms of acute respiratory infection (ARI) and obtained naso- and oropharyngeal samples for real-time reverse transcriptase polymerase chain reaction (RT-PCR). We used multivariable logistic regression to identify risk factors for ICU admission or death, adjusted for age and sex.ResultsFrom May 2008 to July 2012, among 6326 hospitalized ARI cases, 446 (7%) were positive for influenza: of those, 362 (81%) had influenza A and 84 (18%) had influenza B. Fifty nine percent of patients were aged ≤ 5 years, and 10% were aged ≥ 65 years. The median length of hospitalization was 5 days (interquartile range: 5). Eighty of 446 (18%) were admitted to the ICU and 28 (6%) died. Among the 28 deaths, 7% were aged ≤ 6 months, 39% 7–60 months, 21% 5–50 years, and 32% ≥ 50 years. Children aged ≤ 6 months comprised 19% of cases and 22% of ICU admissions. Women of child-bearing age comprised 6% of cases (2 admitted to ICU; 1 death). In multivariable analyses, Santa Rosa site (adjusted odds ratio [aOR] = 10, 95% confidence interval [CI] = 2–50), indigenous ethnicity (aOR = 4, 95% CI = 2–13, and radiologically-confirmed pneumonia (aOR = 5, 95% CI = 3–11) were independently associated with severe disease. Adjusted for hospital utilization rate, annual incidence of hospitalized laboratory-confirmed influenza was 24/100,000 overall, 93/100,000 for children aged < 5 years and 50/100,000 for those ≥ 65 years.ConclusionsInfluenza is a major contributor of hospitalization and death due to respiratory diseases in Guatemala. Further application of proven influenza prevention and treatment strategies is warranted.

Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children

BackgroundDifferentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia.MethodsWestern Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms.ResultsFrom May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination.ConclusionsCombining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis.

SummaryBackgroundPneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya.MethodsWe linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45 000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged <1 year) and a two-dose catch-up campaign for children aged 1–4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends.FindingsBetween May 1, 2002 and March 31, 2015, 44 771 children aged 2–143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses' strikes. In 2002–03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2–59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2–11 months had received at least two doses of PCV10 and 23 298 (62·3%) of 37 416 children aged 12–59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologically-confirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32–0·86), 0·73 (0·54–0·97), and 0·63 (0·31–1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100 000; this value was reduced by 329 per 100 000 at the point of PCV10 introduction.InterpretationOver 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10.FundingGavi, The Vaccine Alliance and Wellcome Trust.

Role of Brain Natriuretic Peptide assay in identifying children with pneumonia complicated by congestive cardiac failure

Background: Pneumonia in children is a leading cause of morbidity and mortality in developing countries. It is often complicated by Congestive Cardiac Failure (CCF), with some of the symptoms similar to those of pneumonia. Brain Natriuretic Peptide (BNP) assay can differentiate cardiac from respiratory-related causes of respiratory distress. Objective: To determine the role of BNP in differentiating isolated pneumonia from pneumonia complicated by CCF. Methods: Over a 12-month period, consecutive children with radiologically-confirmed pneumonia were recruited for the study. Those with complicating CCF were noted. All the children had blood BNP assay done by ELISA, prior to treatment. Biodata was obtained and the children were grouped into those with isolated pneumonia and those with pneumonia complicated by CCF. Results: Fifty children were recruited; of these 26 (52.0%) had isolated pneumonia while 24 (48.0%) had pneumonia with CCF. The median age of the children was 6 months. The median BNP values for the isolated pneumonia group (229.4 ng/l), was significantly lower than that of pneumonia complicated by CCF group (917.3 ng/l); (p = 0.007). ROC showed that a BNP value &gt;550ng/l could identify children with pneumonia complicated with CCF from those with isolated pneumonia with a sensitivity of 70.4% and specificity of 63.4%. Conclusion: A BNP assay prior to treatment of &gt;550ng/l can differentiate children with pneumonia complicated with CCF from those without CCF.

Reliability and validity of the World Health Organization reading standards for paediatric chest radiographs used in the field in an impact study of Pneumococcal Conjugate Vaccine in Kilifi, Kenya.

BackgroundRadiologically-confirmed pneumonia (RCP) is a specific end-point used in trials of Pneumococcal Conjugate Vaccine (PCV) to estimate vaccine efficacy. However, chest radiograph (CXR) interpretation varies within and between readers. We measured the repeatability and reliability of paediatric CXR interpretation using percent agreement and Cohen’s Kappa and the validity of field readings against expert review in a study of the impact of PCV on pneumonia.MethodsCXRs were obtained from 2716 children admitted between 2006 and 2014 to Kilifi County Hospital, Kilifi, Kenya, with clinically-defined severe or very-severe pneumonia. Five clinicians and radiologists attended a three-day training course on CXR interpretation using a WHO standard. All CXRs were read once by two local primary readers. Discordant readings and 13% of concordant readings were arbitrated by a panel of three expert radiologists. To assess repeatability, a 5% median random sample was presented twice. Sensitivity and specificity of the primary readers’ interpretations was estimated against the ‘gold-standard’ of the arbitrators’ results.ResultsOf 2716 CXRs, 2 were uninterpretable and 159 were evaluated twice. The percent agreement and Kappa for RCP were 89% and 0.68 and ranged between 84–97% and 0.19–0.68, respectively, for all pathological findings. Intra-observer repeatability was similar to inter-observer reliability. Sensitivities of the primary readers to detect RCP were 69% and 73%; specificities were 96% and 95%.ConclusionIntra- and inter-observer agreements on interpretations of radiologically-confirmed pneumonia are fair to good. Reasonable sensitivity and high specificity make radiologically-confirmed pneumonia, determined in the field, a suitable measure of relative vaccine effectiveness.

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh’s national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia . This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh's national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia . This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

Burden of Pneumococcal Disease in Northern Togo before the Introduction of Pneumococcal Conjugate Vaccine.

BackgroundS. pneumoniae is a leading cause of meningitis morbidity and mortality in the African meningitis belt, but little is known of its contribution to the burden of pneumonia in the region. We aimed to estimate the incidence of pneumococcal disease in children and adults in northern Togo, before the introduction of pneumococcal conjugate vaccine (PCV).Methods and findingsFrom May 1st 2010 to April 30th 2013, we systematically enrolled all hospitalized patients meeting a case definition of suspected meningitis or clinical pneumonia, residing in Tone or Cinkasse districts, northern Togo and providing informed consent. We collected clinical data and tested biological specimens according to standardized procedures, including bacteriology and PCR testing of cerebro-spinal fluid for meningitis patients and blood cultures and whole blood lytA PCR for pneumonia patients. Chest X-rays (CXR) were interpreted using the WHO methodology. We included 404 patients with meningitis (104 <5 years of age) and 1550 with pneumonia (251 <5 years) over the study period. Of these, 78 (19%) had pneumococcal meningitis (13 <5 years), 574 (37%) had radiologically-confirmed pneumonia (83 <5 years) and 73 (5%) had culture-confirmed pneumococcal pneumonia (2 <5 years). PCV13 serotypes caused 79% (54/68) of laboratory-confirmed pneumococcal meningitis and 83% (29/35) of culture-confirmed pneumococcal pneumonia. Serotype 1 predominated in meningitis (n = 33) but not in pneumonia patients (n = 1). The incidence of pneumococcal disease was 7.5 per 100,000 among children <5 years of age and 14.8 in persons 5 years of age and above in the study area. When considering CXR-confirmed and blood PCR-positive pneumonia cases as likely pneumococcal, incidence estimates increased to 43.7 and 66.0 per 100,000 in each of these age groups, respectively. Incidence was at least 3-fold higher when we restricted the analysis to the urban area immediately around the study hospitals.ConclusionsOur findings highlight the important role of S. pneumoniae as a meningitis and pneumonia-causing pathogen in the African meningitis belt. Pneumococcal disease incidence in our population was substantially lower than expected from global models; we hypothesize that poor access to hospital care led us to substantially underestimate the burden of disease. Surveillance is ongoing and will enable an evaluation of PCV impact, providing novel, high quality data from the region.

Association of RSV-A ON1 genotype with Increased Pediatric Acute Lower Respiratory Tract Infection in Vietnam

Since the initial discovery of RSV-A ON1 in Canada in 2010, ON1 has been reported worldwide, yet information regarding its clinical impact and severity has been controversial. To investigate the clinical relevance of RSV-A ON1,acute respiratory infection (ARI) cases enrolled to our population-based prospective pediatric ARI surveillance at Khanh Hoa General Hospital, Central Vietnam from January 2010 through December 2012 were studied. Clinical-epidemiological information and nasopharyngeal samples were collected. Multiplex PCR assays were performed for screening 13 respiratory viruses. RSV-positive samples were further tested for subgroups (A/B) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region. Statistical analysis was performed to evaluate the clinical-epidemiological characteristics of RSV-A ON1. A total of 1854 ARI cases were enrolled and 426 (23.0%) of them were RSV-positive. During the study period, RSV-A and B had been co-circulating. NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012. RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1. Moreover, multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 (95% CI: 1.37–3.72) times, and radiologically-confirmed pneumonia was 1.98 (95% CI: 1.01–3.87) times greater in ON1 compared to NA1 cases. Our result suggested that ON1 ARI cases were clinically more severe than NA1.

Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study.

BackgroundThere are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.MethodsA prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.ResultsOverall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).ConclusionsIn this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.

Differences upon admission and in hospital course of children hospitalized with community-acquired pneumonia with or without radiologically-confirmed pneumonia: a retrospective cohort study.

BackgroundThe use of chest radiograph (CXR) for the diagnosis of childhood community-acquired pneumonia (CAP) is controversial. We assessed if children with CAP diagnosed on clinical grounds, with or without radiologically-confirmed pneumonia on admission, evolved differently.MethodsChildren aged ≥ 2 months, hospitalized with CAP diagnosed on clinical grounds, treated with 200,000 IU/Kg/day of aqueous penicillin G for ≥ 48 h and with CXR taken upon admission, without pleural effusion, were included in this retrospective cohort. One researcher, blinded to the radiological diagnosis, collected data on demographics, clinical history and physical examination on admission, daily hospital course during the first 2 days of treatment, and outcome, all from medical charts. Radiological confirmation of pneumonia was based on presence of pulmonary infiltrate detected by a paediatric radiologist who was also blinded to clinical data. Variables were initially compared by bivariate analysis. Multi-variable logistic regression analysis assessed independent association between radiologically-confirmed pneumonia and factors which significantly differed during hospital course in the bivariate analysis. The multi-variable analysis was performed in a model adjusted for age and for the same factor present upon admission.Results109 (38.5 %) children had radiologically-confirmed pneumonia, 143 (50.5 %) had normal CXR and 31 (11.0 %) had atelectasis or peribronchial thickening. Children without radiologically-confirmed pneumonia were younger than those with radiologically-confirmed pneumonia (median [IQR]: 14 [7–28 months versus 21 [12–44] months; P = 0.001). None died. The subgroup with radiologically-confirmed pneumonia presented fever on D1 (33.7 vs. 19.1; P = 0.015) and on D2 (31.6 % vs. 16.2 %; P = 0.004) more frequently. The subgroup without radiologically-confirmed pneumonia had chest indrawing on D1 (22.4 % vs. 11.9 %; P = 0.027) more often detected. By multi-variable analysis, Fever on D2 (OR [95 % CI]: 2.16 [1.15-4.06]) was directly and independently associated with radiologically-confirmed pneumonia upon admission.ConclusionThe compared subgroups evolved differently.

Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children

BackgroundAlveolar community-acquired pneumonia (A-CAP) is mostly considered a bacterial disease, mainly pneumococcal. This study was conducted to document the impact of sequential 7-valent and the 13-valent pneumococcal conjugate vaccines (PCV7; PCV13) on emergency room and hospitalization for A-CAP among children <5 years of age. MethodsThis is an ongoing prospective population-based study in southern Israel. The current analysis spans over the period July 2002 through June 2013. A-CAP was defined using the World Health Organization (WHO)’s criteria for radiologically-confirmed pneumonia. PCV7 was introduced in Israel in July 2009 and gradually replaced by PCV13 in November 2010. Pneumococcal conjugate vaccine (PCV) impact was calculated by comparing incidences during 3 pre-defined periods: pre-PCV (2002–2008), PCV7 (2010–2011) and PCV13 (2012–2013). ResultsOverall, 10,142 A-CAP episodes occurred. The annual incidences (per 1,000 inhabitants) in children <5 years old declined from a mean (±standard deviation) of 13.8±0.9 in the pre-PCV period to 11.2±2.7 in the PCV7 period and 7.4 in the PCV13 period, representing a reduction of 13% and 47%, respectively. The overall decrease was significantly faster among outpatients than among hospitalized children (42% and −8%, respectively in the PCV7 period; 68% vs. 32% in hospitalized children in the PCV13 period). While in children 12–23 months a significant decline was observed during the PCV7 and PCV13 periods, significant declines in A-CAP rates were observed only during the PCV13 period in the <12 months and 24–59 months age groups (44% and 46%, respectively). ConclusionsA moderate decline in hospital A-CAP visits in children <5 years old was observed after PCV7 introduction. In contrast, after PCV13 introduction a substantial reduction in all visits was evident.

Cost-effectiveness analysis of the available pneumococcal conjugated vaccines for children under five years in Colombia.

BackgroundPneumococcal diseases in children under five years are common and preventable. In Colombia there are two pneumococcal conjugate vaccines (PCV) that have proved clinical efficacy. The aim was to estimate the cost-effectiveness of 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in terms of prevention of Invasive Pneumococcal Diseases (IPD), radiologically-confirmed pneumonia, and their related mortality, as well as, acute otitis media (AOM) in a cohort of newborns in Colombia.MethodsWe developed an analytical decision tree model with national data including the distribution of pneumococcal serotypes in Colombia between 2009 and 2013. A simulation of vaccination of 90% of newborns in Colombia took place with a time horizon of 5 years. The analysis was done from the Colombian health system perspective. Vaccines efficacy parameters were measured as life-years gained (LYG) and avoided morbidity by pneumococcal diseases; they were determined by a systematic review of literature. A health insurance company provided the costs. A probabilistic and a univariate sensitivity analysis for epidemiological, efficacy and cost parameters were done.ResultsAfter 5 years projection, PCV13 would prevent 437 deaths due to pneumococcal infections versus 321 that would be prevented by PCV10, compared to no vaccination. PCV13 would generate 25 396 LYG, and PCV10 would generate 18 708 LYG. Medical costs avoided would be US$ 19 479 395 for PCV13 and US$ 13 703 271 for PCV10. Compared to no vaccination, PCV13 and PCV10 were cost-effective, with an incremental cost-effectiveness ratio (ICER) of US$ 489.26 and US$ 813.41 per additional LYG, respectively; besides, PCV13 was dominant over PCV10 due to lower costs and better outcomes.ConclusionPCV13 is a cost-saving strategy compared with PCV10, as part of a universal coverage vaccination program in Colombian children under one year. PCV13 is expected to lead to a greater decrement in infant mortality from pneumococcal diseases, and a higher cost saving by preventing more pneumococcal diseases compared with PCV10 in a 5 years projection.

Early indication for a reduced burden of radiologically confirmed pneumonia in children following the introduction of routine vaccination against Haemophilus influenzae type b in Nha Trang, Vietnam

IntroductionDespite the global success of Hib vaccination in reducing disease and mortality, uncertainty about the disease burden and the potential impact of Hib vaccination in Southeast Asia has delayed the introduction of vaccination in some countries in the region. Hib vaccination was introduced throughout Vietnam in July 2010 without catch-up. In an observational, population based surveillance study we estimated the impact of routine Hib vaccination on all cause radiologically confirmed childhood pneumonia in Nha Trang, Vietnam. Materials and methodsIn 2007 active hospital based surveillance was established in Khanh Hoa General Hospital, the only hospital in Nha Trang, Khanh Hoa province. Nasopharyngeal samples and chest radiographs are taken routinely from all children diagnosed with acute respiratory illness on admission. For admissions between 02/2007 and 03/2012 chest radiographs were interpreted for the presence of WHO primary endpoint pneumonia and nasopharyngeal swabs were analysed by PCR for the presence of Influenza A or B, RSV and rhinovirus. We employed Poisson regression to estimate the impact of Hib vaccination on radiologically confirmed pneumonia (RCP) while statistically accounting for potential differences in viral circulation in the post vaccination era which could have biased the estimate. ResultsOf 3151 cases admitted during the study period, 166 had RCP and major viruses were detected in 1601. The adjusted annual incidence of RCP in children younger than 5 years declined by 39% (12–58%) after introduction of Hib vaccination. This decline was most pronounced in children less than 2 years old, adjusted IRR: 0.52 (0.33–0.81), and no significant impact was observed in the 2–4 years old who were not eligible for vaccination, adjusted IRR: 0.96 (0.52–1.72). DiscussionWe present early evidence that the burden of Hib associated RCP in Nha Trang before vaccination was substantial and that shortly after introduction to the routine childhood immunisation scheme vaccination has substantially reduced that burden.

Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine on Radiologically-Confirmed Pneumonia in Young Children in Pakistan

The effectiveness of Haemophilus influenzae type b (Hib) vaccine in preventing severe pneumonia in Asian children has been questioned, and many large Asian countries yet to introduce Hib conjugate vaccine in immunization programs. The primary objective of this study was to assess Hib conjugate vaccine effectiveness (VE) on radiologically-confirmed pneumonia in children born after introduction of Hib conjugate vaccine in Pakistan. A matched case-control study enrolled cases of radiologically-confirmed pneumonia in several hospitals serving low-income populations during 2009-2011. Cases were matched by age and season with 3hospital and 5 neighborhood controls. Pneumonia was diagnosed using standardized World Health Organization criteria for chest radiograph interpretation. Matched OR were estimated for VE. A total of 1027 children with radiologically-confirmed pneumonia were enrolled; 975 cases, 2925hospitalcontrols, and 4875 neighborhood controls were analyzed. The coverage for 3 doses of diphtheria-tetanus-pertussis-hepatitis B-Hib conjugate vaccine was 13.7%, 18%, and 22.7% in cases, hospital controls and neighborhood controls, respectively. Estimated Hib VE for radiologically-confirmed pneumonia was 62%with 3 doses of vaccine using hospital controls and 70% using neighborhood controls. Hib conjugate vaccine prevented a significant fraction of radiologically-confirmed pneumonia in children in Pakistan. Maximizing impact on child survival needs improved immunization coverage.

Haemophilus influenzae Type b Disease among Children in Rural Mozambique: Impact of Vaccine Introduction

Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.

Incidence of Radiologically-Confirmed Pneumonia and Haemophilus influenzae Type b Carriage before Haemophilus influenzae Type b Conjugate Vaccine Introduction in Central Vietnam

To determine the incidence of radiologically-confirmed pneumonia (RCP) and Haemophilus influenzae type b (Hib) carriage in central Vietnam as a baseline data before Hib conjugate vaccine introduction. In the context of ongoing population-based prospective, hospitalized acute respiratory infection surveillance study, a cross-sectional Hib carriage study was conducted among 1000 children < 5 years of age livingin NhaTrang, Vietnam in June 2010, 1 month before the nationwide introduction of Hib conjugate vaccine in Vietnam. The incidence of RCP hospitalizations among children < 5 years of age was 3.3 per 1000 children. The highest incidence was observed among children 12-23 month age group (8.3 per 1000). Haemophilus influenzae carriage was detected in 37% of the children and Hib carriage rate was 3%. Eighty-two percent of the Haemophilus influenzae had TEM β-lactamase resistance gene. The presence of 6 or more family members was associated with an increased rate of Hib carriage (P = .04). Incidence of RCP and Hib carriage in this cross-sectional survey are lower compared with other studies. Continued surveillance for invasive Hib disease and sequential Hib carriage surveys are needed to support future assessments of the impact of Hib conjugate vaccine in Vietnam.

Cost-effectiveness of pneumococcal conjugate vaccines of 7, 10, and 13 valences in Colombian children

Currently there are three pneumococcal conjugate vaccines with different coverage of serotypes for use in children under one year. We evaluate the cost-effectiveness of the introduction of pneumococcal conjugate vaccines of 7, 10, and 13 valences in the Colombian EPI. A Markov model, which followed a cohort of children under one year to life expectancy, was developed. Parameters of occurrence and care costs were based on data from National Health System and literature review. PCV-7 is a dominated strategy. PCV-10 and PCV-13 were each compared to no vaccination or PCV-10 vaccination, respectively. A 2+1 schedule and a vaccination price of US$ 14.00, US$ 14.85 and US$ 16.34 per dose were assumed in the base case for PCV-7, -10, and PCV-13 vaccines. Introduction of PCV-13 rather than PCV-10 increases the number of life years gained (LYG). From the societal perspective, in the 'competing choice' framework cost per LYG was US$ 1837 with PCV-10 and US$ 9514 with PCV-13, while PCV-7 is a dominated strategy. The ICER of PCV-13 is above the per capita Gross Domestic Product. Incremental cost-effectiveness ratios (ICERs) were influenced mainly by effectiveness against radiologically-confirmed pneumonia and AOM, vaccine price, and discount rate. Routine vaccination against Streptococcus pneumoniae in Colombia would be cost-effective with PCV-10, with ICER below the per-capita GDP, but its inclusion requires evaluating the budget impact. PCV-13 would prevent more disease and deaths with a higher LYG, but PCV-10 would save more cost to the healthcare system due its higher impact in the prevention of AOM. There is limitation in the clinical evidence of both strategies.