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.

The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review.

BACKGROUND: Two of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST). METHODS: We systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (≥ 2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST. RESULTS: We identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST. CONCLUSIONS: Few RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines.

Surveillance of bacterial meningitis in the country of Georgia, 2006-2010.

Bacterial meningitis remains important cause of morbidity and mortality worldwide, particularly in developing countries. This study analyzed the data from sentinel surveillance for bacterial meningitis among children <5 years of age hospitalized in largest children's hospital in Tbilisi, capital of Georgia and adult patients hospitalized in infectious diseases hospital during 2006-2010 with suspected bacterial meningitis. The surveillance is conducted by National Center for Disease Control and Public Health (NCDCPH). The number of patients with identified organism was 127 (19 %). In the subsample of patients with laboratory confirmed bacterial meningitis Streptococcus pneumoniae was the most frequently isolated organism (67 cases, 52.8 %), followed by. influenza (17 cases, 13.4 %) and Neisseria meningitidis (16 cases, 12.6 %). The number of patients with suspected TB meningitis was 27 (21.3 %). The overall case fatality rate in the subgroup of patients with identified organism was 12.3 %. The highest mortality was observed among TB patients (22.2 %) with 14.3 % mortality for N. meningitidis and 10.3 % for S. pneumoniae. No lethal outcome was observed among patients with Haemophilus influenzae.

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.

The causative organisms of bacterial meningitis in Korean children in 1996-2005.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy.

Reduction of meningitis and impact on under-5 pneumonia after introducing the Hib vaccine in the Kingdom of Tonga.

AIMS: To document the impact of Hib vaccine on Haemophilus influenzae (Hi) invasive disease, meningitis and inpatient pneumonia in children under 5 in the Kingdom of Tonga. METHODS: Cases of meningitis and pneumonia were sourced from the paediatric discharge book from 1 January 2000 to 2 November 2007 and from computerised discharge records from Vaoila Hospital on the island of Tongatapu where approximately 70% of the total population resides. Laboratory-confirmed cases were sourced from the microbiology laboratory register over the same period. RESULTS: Prior to the introduction of Hib vaccine in 2005, there were, on average, 5.6 cases of invasive Hi disease per year. In the 22 months after Hib vaccine introduction, there was only one case of invasive Hi disease. This corresponds to a fall in the annual incidence of invasive Hib disease from 54.3 to 5.1/100,000 children under 5 years of age. The annual incidence of inpatient pneumonia has fallen by 28.3% from 1007.6 to 722.8/100,000 children under 5 in the 22 months after introducing the vaccine. CONCLUSION: Hib vaccine has reduced invasive Hi disease and Hi meningitis in Tonga. The reduction in inpatient pneumonia is more likely a reflection of annual fluctuations in viral pneumonia than of a reduction in Hib pneumonia, but ongoing surveillance is recommended.

[Management strategy for pediatric presumptive bacterial meningitis (diagnosis, surveillance, follow-up)]. / Stratégie de prise en charge (diagnostic, surveillance, suivi) d'une méningite présumée bactérienne de l'enfant.

The epidemiology of bacterial meningitis has changed since the last French consensus in 1996, mainly because of more frequent Haemophilus influenzae B and pneumoccocus vaccination. A research PubMed and Cochrane databases was performed for articles published within the past 12 years, mentioning the diagnosis, surveillance, and follow-up of presumed bacterial meningitis in children. Sixty-one references were included among the 1606 on PubMed and 50 on the Cochrane databases. Additional articles (n=35) were identified using the references of selected articles. The definition of bacterial meningitis was reviewed, particularly when the causal agent was not identified. Clinical and biological criteria for the diagnosis and the place of brain imaging were updated. Guidelines available after the common use of Haemophilus influenzae vaccination were analyzed with their level of evidence. Initial surveillance data and risk factors associated with death or poor outcome were reviewed. The short and long-term follow-up was also analyzed to identify the proper follow-up for children.

[Childhood bacterial meningitis in the Norwegian county Sør-Trøndelag 1988 - 2007]. / Bakteriell meningitt hos barn i Sør-Trøndelag 1988 - 2007.

BACKGROUND: Bacterial meningitis is a severe and feared disease. We have studied bacterial meningitis in children in Sør-Trøndelag county during a 20-year period from 1988 to 2008. MATERIAL AND METHODS: Medical records of children (in-patients) with spinal fluid findings or a clinical diagnosis of bacterial meningitis, at St. Olavs Hospital, were retrospectively reviewed. RESULTS: 112 cases of bacterial meningitis were registered in children below 16 years of age in Sør-Trøndelag county between 1988 and 2008. Children younger than 2 years had the highest occurrence, with a mean annual incidence of 42.3 per 100,000, whereas the incidence among children in the age group 2 to 16 was 5.7 per 100,000. We observed a decline in the occurrence from 19.1 per 100,000 in the period 1988 - 1991, to 6.9 per 100,000 in the period 2003 - 2006. 31 cases of Haemophilus influenzae type B, 26 cases of Neisseria meningitidis group B, 26 of Streptococcus pneumoniae and 19 cases with other pathogens were registered. The occurrence of H influenzae and N meningitidis have declined over the entire period, whereas S pneumoniae has increased. 6/112 children died (5.4 %) and 34 developed sequelae (30.4 %). In a multiple logistic regression analysis, the maximal value of C-reactive protein was associated with an increased risk of developing sequelae, adjusted for age and triggering microbe. INTERPRETATION: The incidence of bacterial meningitis among children in Sør-Trøndelag has decreased significantly over the last 20 years, and meningitis is now a rare disease. Bacterial meningitis is most common among children below the age of two, and is still associated with a substantial mortality and risk of long-term neurological sequalae.

Invasive Haemophilus influenzae Serotype a Infection in Children: Clinical Description of an Emerging Pathogen-Alaska, 2002-2014.

BACKGROUND: Invasive infections from Haemophilus influenzae serotype a (Hia) have been reported with increasing frequency, especially among indigenous populations. However, there are limited population-based studies of clinical severity. We studied invasive Hia infections in Alaska to determine clinical characteristics, mortality and sequelae. METHODS: We defined an invasive Hia infection as the first detection of Hia from a usually sterile site in a child <10 years of age from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases Surveillance System and reviewed medical charts up to 2 years after reported illness. RESULTS: We identified invasive Hia infections in 36 children, 28 (78%) <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without documented underlying illness. Overlapping clinical presentations included meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%); and bone, joint or soft tissue infections in 10 children (22%). In 4 other children, no source of invasive infection was identified. Intensive care was provided for 11 children (31%); 12 children (33%) required surgical intervention. One year after infection, 4 children (11%) had died from Hia, and 5 children (14%) had ongoing neurologic sequelae. CONCLUSIONS: Invasive Hia infections in Alaska occurred predominantly in Alaska Native infants in rural communities. Although one-third of children had preexisting conditions, most cases occurred without known comorbidity. Clinical syndromes were frequently severe. One year after infection, 1 in 4 children had either died or had neurologic sequelae. An effective vaccine would prevent significant morbidity and mortality in affected populations.

Impact of the Haemophilus influenzae type b vaccination program on HIB meningitis in Brazil.

This study aimed to evaluate the impact of vaccination against Haemophilus influenzae type b (HIB) in Brazil on the morbidity, mortality, and case fatality of HIB meningitis, using the Ministry of Health database and population data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística--IBGE). Impact was evaluated through a time series analysis (1983-2002), using regression forecasting (RF) by dividing the time series into two periods: (a) historical (1983-1998) and (b) validation (1999-2002). Impact of the vaccination was positive, although more significant for incidence and mortality than for case fatality rates.

The epidemiology of Haemophilus influenzae type b meningitis in Burkina Faso.

BACKGROUND: Haemophilus influenzae type b (Hib) disease burden studies are important to conduct in African countries that plan to introduce vaccine so that vaccine impact can be documented. METHODS: We implemented population-based meningitis surveillance in 3 districts of Burkina Faso for 12 months each during 2002-2003 and 2004-2005 using polymerase chain reaction, culture and antigen detection. RESULTS: Lumbar puncture was performed on 1686 patients and 112 had Hib identified. Persons <1, <5, 5-14 and 15+ years of age had annual Hib meningitis incidences of 97, 34, 2.1 and 0.55 per 100,000, respectively; overall case fatality proportion was 25%. During the historic meningitis epidemic season months of December through April, the proportion of purulent cerebrospinal fluid among children aged <5 years that yielded Hib was 27% compared with 30% during other months. Twenty-five of 98 persons with information available were treated with only one or 2 doses of oily chloramphenicol. Among children age <5 years with Hib meningitis, 28% were pretreated with antimalarials and antimalarial pretreatment was associated with delay in hospitalization. CONCLUSIONS: In Burkina Faso, Hib meningitis incidence and case fatality proportion are high and thus vaccine could have a substantial impact. While awaiting well-implemented routine infant Hib vaccination, empiric case management for pediatric meningitis in sub-Saharan Africa must recognize that Hib is likely even during the epidemic season. In malaria-endemic areas, pediatric Hib meningitis case management may be adversely affected by the similar presentation of these 2 diseases.

[Trends in Haemophilus influenzae type b meningitis in Brazil in children under five years of age from 1983 through 2002]. / Tendência das meningites por Haemophilus influenzae tipo b no Brasil, em menores de 5 anos, no período de 1983 a 2002.

The study was based on an ecological design using a historical time series (1983-2002), related to Haemophilus influenzae type b meningitis in Brazil. Incidence, mortality and case-fatality rates, as well as trends in incidence and morbidity-mortality were estimated in children less than 5 years of age. Polynomial regression analysis was used to analyze trends, adopting a significance level of 0.05. 43.9% of confirmed cases occurred in infants less than 1 year old and 38.7% in children 1-4 years old. The observed rates were also highest in these two age strata. The incidence and mortality rates showed an increasing trend, until approximately 1999, when a quick decline was observed. The study results reinforce the effectiveness of the Vaccination Program against HIB in Brazil, which benefited age ranges that did not receive the vaccine (Herd Immunity).

[A study of bacterial meningitis in Hokkaido between 1999 and 2003].

We evaluated 83 children with bacterial meningitis in 67 of 81 insitutions in Hokkaido, Japan between 1999 and 2003 by questionnaire. The incidence of bacterial meningitis in children aged < 5 years and 5 < or =, < 10 years was 6.3 and 0.7 cases per 100, 000 children/year. The incidences of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus agalactiae in children aged < 5 years were 3.7, 1.4 and 0.8. Median age was 13 months ranging from 0 day to 9 years. Seventy-four (89.1%) of the total were less than 5 years old with 39 (47.0%) less than 1 year old. Major causative organisms were H. influenzae in 51 patients, S. pneumoniae in 18, S. agalactiae in 9 and E. coli in 3. Four deaths occurred, giving an overall case mortality rate of 4.8%. Sequelae were seen at discharge in 25.3%, predominantly epilepsy, hearing loss, and developmental delay of varying severity. The frequency of poor prognosis was 55.6% for patients with meningitis due to S. pneumoniae compared with 21.6% for H. influenzae and 22.2% for S. agalactiae.

Are Haemophilus influenzae infections a significant problem in India? A prospective study and review.

It has been suggested Haemophilus influenzae serotype b (Hib) disease is uncommon in Asia. During 1993--1997, we conducted prospective surveillance of acute infections caused by H. influenzae in 6 academic referral Indian hospitals. The study included 5798 patients aged 1 month to 50 years who had diseases likely to be caused by H. influenzae; 75% of the patients were aged <5 years. A total of 125 H. influenzae infections were detected, 97% of which were caused by Hib. Of 125 isolates, 108 (86%) were from children aged <5 years, and 11 (9%) were from adults aged >18 years. Sixty-two percent of the patients had meningitis. The case-fatality rate was 11% overall and 20% in infants with Hib meningitis. Up to 60% of all isolates were resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, or erythromycin; 32% were resistant to >/= 3 antimicrobial drugs, but none were resistant to third-generation cephalosporins. These data suggest that available Hib vaccines will benefit Indian children.

Hemophilus influenzae meningitis at the Children's Hospital Medical Center in Boston, 1958 to 1973.

Three hundred ninety-seven children were admitted to the Children's Hospital Medical Center, Boston between 1958 and 1973 with H. influenzae meningitis. The annual rate of admission and the percent of all cases of bacterial meningitis were not changed from that of the preceding decade. The age incidence was strikingly similar to that reported from this hospital for 1920 to 1932.

Postneonatal infant mortality in infants to a neonatal intensive care unit.

The postneonatal infant mortality (PNIM) of 2,205 infants admitted to a neonatal intensive care unit from January 1971 to December 1974 was 44 in 1,000 infants who survived to age 28 days. This rate is approximately ten times that of the general population. Congenital malformations (59%), infections (12%), sudden infant death syndrome (10%), and asphyxial brain damage (10%) were the most common causes of death. One third (26) of the infants remained in the hospital whereas two thirds (52) had been dismissed prior to death. All who remained in the hospital plus 36 who had been dismissed died of severe illnesses that were incompatible with prolonged survival. The remaining PNIM was 10 in 1,000 neonatal survivors. This rate is still twice that of the general population. These deaths occurred in infants who were apparently well at the time of dismissal and subsequent examinations. Sudden infant death syndrome and infections constituted the largest portion of this mortality. Factors contributing to mortality in this group were poor socioeconomic status and low birth weight. Maternal age, race, marital status, and neonatal illnesses including apnea were not significantly related. Factors that appear to be important in the birth of high-risk infants continued to be operative in the postneonatal period, and contribute to a high mortality in apparently normal infants dismissed from the neonatal intensive care unit.

Prediction of morbidity in Hemophilus influenzae meningitis.

A dramatic decrease in mortality from Hemophilus influenzae meningitis has occurred in recent years. Morbidity and long-term sequellae remain significant problems. A follow-up investigation of 73 cases of H. influenzae meningitis seen over a three-year period revealed: 2 deaths, 6 children with major sequellae (retardation, spastic quadriplegia, blindness, persistent seizure disorder), 10 with minor residua, and 55 with no detectable disability. Statistical analysis of clinical parameters demonstrated a significant risk of death or major morbidity in those patients who, at the time of admission, had seizures, coma, hypothermia, shock, age less than 12 months, hemoglobin less than 11 gm/100 ml, pretreatment symptoms for longer than three days, a spinal fluid white blood cell count less than 1,000/cu mm, or a spinal fluid glucose value less than 20 mg/100 ml. Using these parameters, those patients at highest risk of having lasting major morbidity with H. influenzae meningitis can be predicted, allowing more vigorous intensive care which may reduce the mortality and morbidity further.

National trends in Haemophilus influenzae meningitis mortality and hospitalization among children, 1980 through 1991.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccines were licensed for routine use in the United States in December 1987. We compared national trends in deaths and hospitalization from H influenzae meningitis among children < 5 years old before and after Hib conjugate vaccine licensure. METHODS: H influenzae meningitis mortality rates were calculated using data from the 1980 through 1991 computerized national mortality files. Hospitalization rates from H influenzae meningitis were calculated using data from the 1980 through 1991 National Hospital Discharge Surveys. Trends in H influenzae mortality and hospitalization from 1980 through 1887 were compared with trends from 1988 through 1991. Trends for Streptococcus pneumoniae and Neisseria meningitidis meningitis were also examined. RESULTS: From 1980 through 1987, mortality from H influenzae meningitis decreased an average of 8.5% each year, compared with a 48% annual decrease from 1988 through 1991 (P < .001 for difference in trends). H influenzae meningitis hospitalization rates increased 1% each year from 1980 through 1987, and decreased an average of 34% each year from 1988 through 1991. There was no significant difference in mortality or hospitalization trends for S pneumoniae or N meningitidis meningitis during the two periods. Among infants, H influenzae meningitis mortality decreased an average of 8% per year from 1980 through 1987 and 43% per year from 1988 through 1991. One- to four-year-old children had similar average annual declines, 8% and 58% for the two periods. Although there were regional differences in the absolute mortality rates, all regions of the country had similar trends in meningitis mortality. CONCLUSIONS: Among US children < 5 years old, we found substantial decreases in deaths and hospitalization from H influenzae meningitis, but not S pneumoniae or N meningitidis meningitis, in the years after Hib conjugate vaccine licensure. These results suggest that the declines in H influenzae meningitis were due primarily to the use of Hib conjugate vaccines.

Epidemiology of Haemophilus influenzae type b meningitis in Manila, Philippines, 1994 to 1996.

BACKGROUND: Effective vaccines against Haemophilus influenzae type b (Hib) have shown impressive results in decreasing Hib meningitis in developed countries. In the Philippines Hib vaccines are not part of the routine immunization given to children. Before a decision can be made to include Hib vaccines in immunization program, epidemiology of Hib meningitis in Manila, Philippines, should first be described. METHODOLOGY: A cohort of 41,592 children <5 years of age in Central Manila was the study population. Confirmed cases between January, 1994, and December, 1996, were obtained from all hospitals in the region. Confirmation of cases was based on positive culture isolated from blood or cerebrospinal fluid (CSF) or Hib antigen identified in CSF with a clinical diagnosis of Hib meningitis. The progress of children with Hib meningitis postinfection was evaluated from hospital records. RESULTS: There were 118 episodes of Hib meningitis identified in the population in the study period. Sequelae occurred in 15% of the total cases, and the case fatality rate was 11%. The annual incidence of Hib meningitis in Manila for children <5 years old was 95 per 100,000. CONCLUSIONS: Hib meningitis in Central Manila is common. The incidence is particularly high in children <6 months old. Adverse neurologic outcomes and a high case fatality rate in children younger than 1 year suggest that a vaccination program would be useful.

A population-based retrospective assessment of the disease burden resulting from invasive Haemophilus influenzae in infants and young children in Santiago, Chile.

Clinical discharge and laboratory records were reviewed in the seven government hospitals that provide care for 93% of the pediatric population of Santiago, Chile, to detect cases of meningitis and other invasive (bacteremia-associated) infections caused by Haemophilus influenzae. infections that occurred in children less than five years of age from January, 1985, through December, 1987, were recorded and matched with census data to calculate incidence rates. The incidence of meningitis and non-meningitis syndromes peaked in the 6- to 11-month age group and tapered sharply after 12 months of age. The city-wide incidence (ca. 21.6 cases/10(5) children less than 5 years of age) is one-third to one-half that reported for the general pediatric population in the United States. However, there is much evidence for under-reporting in Santiago. In Area Norte, served by Roberto del Rio Children's Hospital where H. influenzae has been a subject of research by pediatricians for years, the incidence of invasive H. influenzae infections (42.5/105) is approximately two-fold higher than the rest of Santiago. The cumulative proportions of episodes of H. influenzae disease occurring in successively older age groups closely parallel the pattern seen in the general United States pediatric population. Although only ca. 20% of all episodes occur during the first 6 months of life, nearly 80% of episodes are seen by 18 months of age. Based on the observed incidence rates, the apparent underreporting and the high city-wide case fatality of Hib meningitis (16%), invasive H. influenzae infections represent an important public health problem in Santiago, Chile.