Clinical and Bacteriologic Analysis of Nontypeable Haemophilus influenzae Strains Isolated from Children with Invasive Diseases in Japan from 2008 to 2015.

Haemophilus influenzae type b (Hib) conjugate vaccines have led to dramatic reductions in Hib disease among young children worldwide. Nontypeable H. influenzae (NTHi) is now the major cause of invasive H. influenzae infections. We investigated the clinical characteristics of invasive NTHi diseases among children in Japan, to clarify the pathogenicity of isolated NTHi strains. The mortality rate was 10.7%, with deaths occurring mainly among children with underlying comorbidities. Biotypes II and III were the most common, and most strains (64.3%) had multiple amino acid substitutions at the Asp-350, Ser-357, Ser-385, and/or Met-377 sites of penicillin-binding protein 3. Two strains were ß-lactamase positive and ampicillin-clavulanate resistant. Biofilm indices varied widely, and IS1016 was detected in 10.7% of the strains tested. Moreover, there was wide variation in the characteristics of invasive NTHi strains. NTHi strains, showing great genetic diversity, are responsible for most invasive H. influenzae infections in children in the postvaccine era. Continuous monitoring of NTHi strains responsible for invasive diseases in children is important to detect changes in the epidemiology of invasive H. influenzae infections in the postvaccine era.

Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study.

There is consensus that definitive therapy for infections with H. influenzae should include antimicrobial agents with clinical breakpoints against the bacterium. In Scandinavia, benzylpenicillin is the recommended empirical treatment for community-acquired pneumonia (CAP) except in very severe cases. However, the effect of benzylpenicillin on H. influenzae infections has been debated. The aim of this study was to compare the outcomes of patients given benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as empirical treatment of lower respiratory tract H. influenzae infections requiring hospital care. We identified 481 adults hospitalized with lower respiratory tract infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and early clinical response rates were compared in patients receiving benzylpenicillin (n = 199) and a WSBL (n = 213) as empirical monotherapy. After adjusting for potential confounders, empirical benzylpenicillin treatment was not associated with higher 30-day mortality neither in a multivariate logistic regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91-4.50, p = 0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93-4.92, p = 0.075). Readmission rates did not significantly differ between the study groups, but early clinical response rates were significantly higher in the WSBL group (aOR 2.28, 95% CI 1.21-4.31, p = 0.011), albeit still high in both groups (84 vs 81%). In conclusion, despite early clinical response rates being slightly lower for benzylpenicillin compared to WSBL, we found no support for increased mortality or readmission rates in patients empirically treated with benzylpenicillin for lower respiratory tract infections by H. influenzae.

Child pneumonia - focus on the Western Pacific Region.

Worldwide, pneumonia is the leading cause of death in infants and young children (aged <5 years). We provide an overview of the global pneumonia disease burden, as well as the aetiology and management practices in different parts of the world, with a specific focus on the WHO Western Pacific Region. In 2011, the Western Pacific region had an estimated 0.11 pneumonia episodes per child-year with 61,900 pneumonia-related deaths in children less than 5 years of age. The majority (>75%) of pneumonia deaths occurred in six countries; Cambodia, China, Laos, Papua New Guinea, the Philippines and Viet Nam. Historically Streptococcus pneumoniae and Haemophilus influenzae were the commonest causes of severe pneumonia and pneumonia-related deaths in young children, but this is changing with the introduction of highly effective conjugate vaccines and socio-economic development. The relative contribution of viruses and atypical bacteria appear to be increasing and traditional case management approaches may require revision to accommodate increased uptake of conjugated vaccines in the Western Pacific region. Careful consideration should be given to risk reduction strategies, enhanced vaccination coverage, improved management of hypoxaemia and antibiotic stewardship.

Incidence, Etiology and Outcome of Ventilator-Associated Pneumonia in Patients with Percutaneous Tracheotomy

Although the incidence of ventilator-associated pneumonia (VAP) is very high, there are still many uncertainties about clinical course of VAP among tracheotomized patients. The goal of the present study was to determine the impact of tracheotomy on VAP incidence and etiology, as well as outcome of VAP patients with tracheotomy. The study was conducted in a 15-bed Surgical and Neurosurgical Intensive Care Unit (ICU), Sestre milosrdnice University Hospital Center in Zagreb, Croatia. The study included all patients undergoing only percutaneous tracheotomy during the study period. According to our data, the incidence of VAP among percutaneous tracheotomized patients was 42%, not considering the time between tracheotomy and VAP onset. However, when only patients developing VAP after tracheotomy were taken into account, the incidence of VAP among tracheotomized patients dropped to 8% only. The most commonly isolated bacterium was Staphylococcus aureus, accounting for 17 (37%) isolates, followed by Haemophilus influenzae, accounting for another 10 (22%) isolates. The development of VAP among percutaneously tracheotomized patients was associated with longer total ICU stay (regardless of whether VAP developed before or after tracheotomy), while total duration of mechanical ventilation and mortality rate remained unaffected.

The modA10 phasevarion of nontypeable Haemophilus influenzae R2866 regulates multiple virulence-associated traits.

Non-typeable Haemophilus influenzae (NTHi) is a human restricted commensal and pathogen that elicits inflammation by adhering to and invading airway epithelia cells: transcytosis across these cells can result in systemic infection. NTHi strain R2866 was isolated from the blood of a normal 30-month old infant with meningitis, and is unusual for NTHi in that it is able to cause systemic infection. Strain R2866 is able to replicate in normal human serum due to expression of lgtC which mimics human blood group p(k). R2866 contains a phase-variable DNA methyltransferase, modA10 which switches ON and OFF randomly and reversibly due to polymerase slippage over a long tetrameric repeat tract located in its open reading frame. Random gain or loss of repeats during replication can results in expressed (ON), or not expressed (OFF) states, the latter due to a frameshift or transcriptional termination at a premature stop codon. We sought to determine if the unusual virulence of R2866 was modified by modA10 phase-variation. A modA10 knockout mutant was found to have increased adherence to, and invasion of, human ear and airway monolayers in culture, and increased invasion and transcytosis of polarized human bronchial epithelial cells. Intriguingly, the rate of bacteremia was lower in the infant rat model of infection than a wild-type R2866 strain, but the fatality rate was greater. Transcriptional analysis comparing the modA10 knockout to the R2866 wild-type parent strain showed increased expression of genes in the modA10 knockout whose products mediate cellular adherence. We conclude that loss of ModA10 function in strain R2866 enhances colonization and invasion by increasing expression of genes that allow for increased adherence, which can contribute to the increased virulence of this strain.

Haemophilus influenzae: a potent perinatal pathogen disproportionately isolated from Indigenous women and their neonates.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) bacteraemia in pregnant women is strongly associated with pregnancy loss and preterm delivery. However, the clinical significance of isolation of NTHi from nonsterile sites is unknown. AIMS: To examine the hypothesis that isolation of NTHi from any specimen is associated with adverse perinatal outcomes and to investigate the impression that NTHi is disproportionately isolated from indigenous women and their neonates. MATERIALS AND METHODS: Cases where NTHi was isolated from maternal, fetal or neonatal specimens during the period from 1 July 1997 to 1 July 2009 were identified. Demographic and clinical data were extracted from case notes. Histopathological material was re-reviewed by a perinatal pathologist. Demographic and clinical features of the affected group were compared with the hospital obstetric population. RESULTS: NTHi was isolated from maternal, fetal or neonatal specimens in 97 pregnancies. Two women had NTHi isolated during different pregnancies. Two mothers and 10 neonates were bacteraemic. Indigenous women comprised 28% of pregnancies where NTHi was isolated, compared with 6% of the hospital obstetric population (P < 0.001). Pregnancy loss occurred in six cases (6%). Median gestation at delivery was 33 weeks. Of 96 liveborn neonates, 88 (92%) required admission to a neonatal special care unit. Four liveborn neonates died (4%). Chorioamnionitis was confirmed by histology in 31/33 (93.9%) of placentas examined. CONCLUSIONS: Isolation of NTHi occurred more commonly in indigenous women and neonates. Isolation of NTHi from any obstetric or neonatal specimen is associated with chorioamnionitis, preterm birth, pregnancy loss, early-onset neonatal sepsis and neonatal death.

Adverse events following Haemophilus influenzae type b vaccines in the Vaccine Adverse Event Reporting System, 1990-2013.

OBJECTIVE: To characterize adverse events (AEs) after Haemophilus influenzae type b (Hib) vaccines reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. STUDY DESIGN: We searched VAERS for US reports after Hib vaccines among reports received from January 1, 1990, to December 1, 2013. We reviewed a random sample of reports and accompanying medical records for reports classified as serious. All reports of death were reviewed. Physicians assigned a primary clinical category to each reviewed report. We used empirical Bayesian data mining to identify AEs that were disproportionally reported after Hib vaccines. RESULTS: VAERS received 29,747 reports after Hib vaccines; 5179 (17%) were serious, including 896 reports of deaths. Median age was 6 months (range 0-1022 months). Sudden infant death syndrome was the stated cause of death in 384 (51%) of 749 death reports with autopsy/death certificate records. The most common nondeath serious AE categories were neurologic (80; 37%), other noninfectious (46; 22%) (comprising mainly constitutional signs and symptoms); and gastrointestinal (39; 18%) conditions. No new safety concerns were identified after clinical review of reports of AEs that exceeded the data mining statistical threshold. CONCLUSION: Review of VAERS reports did not identify any new or unexpected safety concerns for Hib vaccines.

Childhood very severe pneumonia and meningitis-related hospitalization and death in Yemen, before and after introduction of H. influenzae type b (Hib) vaccine.

Haemophilus influenzae type b (Hib) vaccine was included in the Yemen immunization programme in 2005. This study compared the rates of very severe pneumonia and all-cause meningitis hospitalization and death, before and after introduction of conjugate Hib vaccine, and reports the results of the 2010 bacterial meningitis surveillance. A retrospective analysis was made of data collected for 2000-2010 for all children aged 2-60 months in the main children's hospital in Sana'a. Compared with the pre-Hib vaccination period, the post-Hib period showed significant and impressive reductions in the rates of hospitalization and death for all-cause meningitis. However, hospitalization and death for very severe pneumonia improved only modestly, and there was evidence of a decreasing but non-significant trend indicting that very severe pneumonia was a non-specific endpoint with multi-etiologies (both viral and bacterial). Very severe pneumonia remains the leading cause of severe morbidity and death for young children, particularly those aged < 12 months.

Treatment of Haemophilus bacteremia with benzylpenicillin is associated with increased (30-day) mortality.

BACKGROUND: Optimal antibiotic treatment strategies of Haemophilus infections are still needed. Therefore, 30-day case fatality rate (CFR) of Haemophilus bacteremia and efficacy of various antibiotic treatment regimes were studied. METHODS: All episodes of Haemophilus bacteremia in the former Copenhagen County during the period 2000-9 were included in the study. Clinical and biochemical findings and outcome were collected retrospectively from medical records. RESULTS: 105 consecutive episodes were identified (median age: 69 years, with only 4 children <16 years), 72% were due to non-typeable -, 16% to typeable H. influenzae, and 11% to other Haemophilus species. Pneumonia was the most common primary focus (in 48%), and 58% of the patients had Charlson comorbidity index > 1. Definitive antibiotic therapy was in 26 cases benzylpenicillin, in 12 cases aminopenicillins, in 50 cases cefuroxime and in 16 cases broadspectrum antibiotics, whereas 1 palliative case died without start of therapy. Whereas the use of broadspectrum antibiotics was related to the severity of the disease (admittance to ICU, need for assisted ventilation or hemodialysis, septic shock), no significant difference in clinical features was demonstrated for therapy with benzylpenicillin, aminopenicillin or cefuroxime, except benzylpenicillin was rarely administered to immunosuppressed patients. The CFR was 22% (23/105). The choice of empiric antibiotic therapy was not significantly associated with mortality (adequate vs. inadequate treatment: 23% (21/93) vs. 17% (2/12), respectively, P > 0.05). In contrast, definite antibiotic therapy with cefuroxime or aminopenicillins resulted in a significantly lower CFR than treatment with benzylpenicillin (12% (6/50) or 0% (0/12) vs. 39% (10/26), respectively, Log rank test P < 0.02). When adjustments were made for other identified risk factors in bivariate logistic regression analysis, treatment with cefuroxime was still were found to be associated with a significantly lower CFR than for benzylpenicillin: OR: 0.21 (0.06-0.69), P = 0.01 (hospital-acquired bacteremia), OR: 0.27 (0.08-0.91), P = 0.04 (polymicrobial episodes), OR: 0.16 (0.04-0.59), P = 0.006 (admittance at intensive care unit), OR: 0.22 (0.06-0.82), P = 0.02 (alcohol abuse), OR: 0.15 (0.04-0.60), P = 0.008 (altered mental state), OR: 0.22 (0.07-0.71), P = 0.01 (temperature < 38 °C), OR: 0.23 (0.07-0.79), P = 0.02 (septic shock), OR: 0.21 (0.06-0.69), P = 0.01 (mechanical ventilation). CONCLUSION: Our results suggest that, after susceptibility testing, cefuroxime or aminopenicillins are preferable to benzylpenicillins as definitive therapy for Haemophilus bacteremia.

Current epidemiology and trends in invasive Haemophilus influenzae disease--United States, 1989-2008.

BACKGROUND: With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. METHODS: Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. RESULTS: During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. CONCLUSIONS: Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States.

Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA.

Since the introduction of the Haemophilus influenzae type b vaccine, the incidence of invasive H. influenzae type b disease among children has fallen dramatically, but the effect on invasive H. influenzae disease among adults may be more complex. In this population-based study we examined the epidemiology and outcomes of invasive disease caused by typeable and nontypeable H. influenzae among Utah adults during 1998-2008. The overall incidence increased over the study period from 0.14/100,000 person-years in 1998 to 1.61/100,000 person-years in 2008. The average incidence in persons >65 years old was 2.74/100,000 person-years, accounting for 51% of cases and 67% of deaths. The incidence was highest for nontypeable H. influenzae (0.23/100,000 person-years), followed by H. influenzae type f (0.14/100,000 person-years). The case-fatality rate was 22%. The incidence of invasive H. influenzae in Utah adults appears to be increasing. Invasive H. influenzae infection disproportionately affected the elderly and was associated with a high mortality rate.

A mouse model of lethal synergism between influenza virus and Haemophilus influenzae.

Secondary bacterial infections that follow infection with influenza virus result in considerable morbidity and mortality in young children, the elderly, and immunocompromised individuals and may also significantly increase mortality in normal healthy adults during influenza pandemics. We herein describe a mouse model for investigating the interaction between influenza virus and the bacterium Haemophilus influenzae. Sequential infection with sublethal doses of influenza and H. influenzae resulted in synergy between the two pathogens and caused mortality in immunocompetent adult wild-type mice. Lethality was dependent on the interval between administration of the bacteria and virus, and bacterial growth was prolonged in the lungs of dual-infected mice, although influenza virus titers were unaffected. Dual infection induced severe damage to the airway epithelium and confluent pneumonia, similar to that observed in victims of the 1918 global influenza pandemic. Increased bronchial epithelial cell death was observed as early as 1 day after bacterial inoculation in the dual-infected mice. Studies using knockout mice indicated that lethality occurs via a mechanism that is not dependent on Fas, CCR2, CXCR3, interleukin-6, tumor necrosis factor, or Toll-like receptor-4 and does not require T or B cells. This model suggests that infection with virulent strains of influenza may predispose even immunocompetent individuals to severe illness on secondary infection with H. influenzae by a mechanism that involves innate immunity, but does not require tumor necrosis factor, interleukin-6, or signaling via Toll-like receptor-4.

Epidemiology and population structure of Haemophilus influenzae causing invasive disease.

This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014-2019), reporting its evolution from a previous period (2008-2013) and analysing the non-typeable H. influenzae (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive H. influenzae disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7-14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10-17.6 % and 0-4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 (n=20) and 5 sequence types (STs) (n=10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with ß-lactam resistance. Invasive H. influenzae disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing ß-lactam resistance over time.

Exploring factors associated with acquisition and chronicity of infection in bronchiectasis: A population-based study.

INTRODUCTION: Chronic infection is associated with adverse outcomes among people with bronchiectasis. However, it is not known which factors are associated with a bacterial infection, and with persistence of an infection after the first episode. We aimed to determine factors associated with a new infection and with chronicity of Pseudomonas aeruginosa (PA) and H. influenzae (HI), the most common organisms in bronchiectasis infection. METHODS: Using an Israeli population database, we identified individuals diagnosed with bronchiectasis. Cox proportional hazard models were used to assess risk factors for first isolation and Logistic regression for chronicity of infection after a first isolation of PA and HI. RESULTS: We included 1305 people with a median of 5 respiratory samples per individual. PA was initially isolated in 297 people, of whom 97 (33%) developed chronic PA infection. HI was newly identified in 169 people, of whom 39 (23%) developed chronic infection (p = 0.029). Factors associated with increased risk of a new infection with PA were COPD (HR 1.87 [1.52-2.28], previous isolation of HI (HR 1.38 [1.07-1.78]), and alcohol abuse (HR 2.22 [1.13-4.3]). Younger age was associated with increased risk of HI infection, while COPD was associated with a lower risk of HI infection. Prescription of an anti- PA antibiotic was associated with chronic PA after a new infection (OR = 1.8 [1.09-2.9], p = 0.02). A landmark analysis showed that survival was worse in people with chronic PA infection vs. single or intermittent infection (Log rank: p = 0.034) CONCLUSIONS: Younger age and presence of PCD are associated with a new isolation of HI. A new infection with PA is associated with previous HI infection, PCD, COPD, and alcohol abuse. Unexpectedly, treatment with appropriate anti-PA antimicrobials was not associated with a reduced risk of chronicity.

Concurrent infection of Avibacterium paragallinarum and fowl adenovirus in layer chickens.

The diagnosis of a concurrent infection of Avibacterium paragallinarum and fowl adenovirus (FAdV) in an infectious coryza-like outbreak in the outskirt of Beijing is reported. The primary signs of the infection were acute respiratory signs, a drop in egg production, and the presence of hydropericardium-hepatitis syndrome-like gross lesions. Laboratory examination confirmed the presence of A. paragallinarum by bacterial isolation and a species-specific PCR test. In addition, conventional serotyping identified the isolates as Page serovar A. Fowl adenovirus was isolated from chicken liver specimen and identified by hexon gene amplification. In addition, histopathologic analysis and transmission electron microscopy examination further confirmed the presence of the virus. Both hexon gene sequencing and phylogenetic analysis defined the viral isolate as FAdV-4. The pathogenic role of A. paragallinarum and FAdV was evaluated by experimental infection of specific-pathogen-free chickens. The challenge trial showed that combined A. paragallinarum and FAdV infection resulted in more severe clinical signs than that by FAdV infection alone. The concurrent infection caused 50% mortality compared with 40% mortality by FAdV infection alone and zero mortality by A. paragallinarum infection alone. To our knowledge, this is the first report of A. paragallinarum coinfection with FAdV. The case implies that concurrent infections with these 2 agents do occur and more attention should be given to the potential of multiple agents during disease diagnosis and treatment.

National, regional, and state-level burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in India: modelled estimates for 2000-15.

BACKGROUND: India accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015. METHODS: In this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk. FINDINGS: Between 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1-59 months fell from 166 000 (uncertainty range [UR] 110 000-198 000) to 68 700 (44 600-86 000), while Hib deaths fell from 82 600 (52 300-112 000) to 15 600 (9800-21 500), representing a 58% (UR 22-78) decline in pneumococcal deaths and an 81% (59-91) decline in Hib deaths. In 2015, national mortality rates in children aged 1-59 months were 56 (UR 37-71) per 100 000 for pneumococcal infection and 13 (UR 8-18) per 100 000 for Hib. Uttar Pradesh (18 900 [UR 12 300-23 600]) and Bihar (8600 [5600-10 700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900-12 700]) and Odisha (1100 [700-1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118 000 (UR 69 000-140 000) total pneumococcal deaths could have occurred in 2015 in India. INTERPRETATION: Pneumococcal and Hib mortality have declined in children aged 1-59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India. FUNDING: Bill & Melinda Gates Foundation.

The role of Haemophilus influenzae type b in fatal community-acquired pneumonia in Chinese children.

To analyze the role of Haemophilus influenzae type b in children's death resulting from severe pneumonia conventional PCR, Southern blotting and in situ PCR were evaluated for the detection of Hib in 202 paraffin-embedded lung tissue autopsy samples from children with fatal outcome of pneumonia in China during the period of 1953-2002. The results indicate that Hib was a cause of fatal pneumonia in 36 (17.8%) of 202 samples.

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.

Clinical profile of pleural empyema and associated factors with prolonged hospitalization in paediatric tertiary centre in Angola, Luanda.

In a case series of 152 children aged from 2 to 132 months will pleural emphema from a paediatric tertiary hospital in Luanda, Angola between September 2004 and March 2005, the authors found a high prevalence of anaemia and malnutrition. The most prevalent bacteria in pleural fluid were: D pneumoniae, Haemophyllus and S aureus. The median for hospital stay was 25 days. The lethality was 7.8% and was not statistically associated with malnutrition, although this variable was associated, in multivariate analysis, with prolonged hospitalization time.