Use Of Hib Vaccine Research Articles

Widespread of non-typeable Haemophilus influenzae with high genetic diversity after two decades use of Hib vaccine in China.

BackgroundThe aim of this study was to analyze the microbiological characteristics of nasopharyngeal carriage Haemophilus influenzae isolates collected from children with respiratory infections in Beijing hospital and Youyang Hospital of China.MethodsThe serotypes of all isolates were determined using latex agglutinated antisera (a‐f). The minimum inhibitory concentrations (MICs) of 11 antibiotics were determined using E‐test strips. For the beta‐lactamase‐negative ampicillin‐resistant (BLNAR) isolates, ftsI gene was sequenced based on fragments amplified by PCR. STs of H influenzae isolates were determined by multi‐locus sequence typing.ResultsThe overall carriage rate of H influenzae in the study population was 9.1% (362/3984). One hundred and ninety H influenzae isolates which were selected in our study were non‐typeable (NTHi) and 44 (23.2%) of them were positive for β‐lactamase. All isolates were susceptible to ceftriaxone and levofloxacin. Susceptibility rates to erythromycin and sulfamethoxazole‐trimethoprim in Beijing were significantly higher than Youyang (P < .05). Thirty‐six BLNAR isolates were identified. The MLST analysis showed 108 STs in 190 isolates, the most common of which were ST408 (11, 5.8%), ST914 (10, 5.3%), ST57 (9, 4.7%), and ST834 (6, 3.2%). Twelve STs were detected in both of the study sites, which covered 63 isolates.ConclusionsAll isolates in the present study were NTHi, which suggested widespread of this type in China. The BLNAR isolates were detected more frequently than before. Because high genetic diversity of NTHi isolates of H influenzae exists worldwide, it is important to continuously monitor these bacteria in the future.

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15.

SummaryBackgroundPneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015.MethodsUsing WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use.FindingsWe estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015.InterpretationThe widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia.FundingBill & Melinda Gates Foundation.

Nontypeable Haemophilus influenzae (NTHi).

In this infographic the diseases caused by nontypeable Haemophilus influenzae (NTHi), including otitis media, are discussed. Encapsulated type b Haemophilus influenzae (Hib) was responsible for most of the invasive disease (meningitis) prior to the use of Hib vaccines. As Hib vaccines have no effect on infections due to nontypeable H. influenzae (NTHi), in areas where Hib vaccines are used, nontypeable strains are now the most common cause of invasive disease. Moreover, NTHi contributes to the ∼21000 otitis media (OM)-associated deaths per year. Due to this collective global morbidity and mortality, concerted vaccine development is underway. In addition to preventing disease, an effective vaccine will likely help to mitigate the global crisis of antibiotic resistance. Since 1973, ampicillin resistance due to NTHi's production of β-lactamase has been recognized; however, a significant concern is the more recent emergence and spread of β-lactamase-negative-ampicillin-resistant (BLNAR) strains in many regions of the world. As such, H. influenzae is one of 12 bacterial pathogens that are considered priority pathogens by the World Health Organization.

Utilization pattern of Haemophilus influenza type b vaccine in eight provinces of China

ABSTRACTObjective: In China, Hib vaccine is a private-sector vaccine that is an option for parents to select to give to their children; it must be paid for out-of-pocket because it is not included in the government's Expanded Program on Immunization (EPI). We evaluated utilization patterns of Hib vaccine to provide evidence in support of development of a national Hib vaccination strategy. Methods: We obtained lists of children from immunization information systems (IIS) of counties or districts in 8 provinces of China. Using these lists, we selected 10 children at random from each birth cohort from 2008 through 2012. We obtained Hib vaccination dates from official vaccination certificates. The target sample size was 1,000 children. Results: We were able to obtain records for 978 subjects of the selected subjects; of these, 44.79% had received at least 1 dose of Hib vaccine, and 15.54%, 5.83%, 12.27%, and 11.15% had received one, two, three, and four doses, respectively. Per capita GDP was positively correlated with receipt of at least one dose of Hib vaccine. Among the 438 subjects who received Hib vaccine, 27% received 1 dose after 12 months of age; 15%, 7%, and 23% received one of three other patterns of Hib vaccination recommended by the World Health Organization (WHO) [a 3-dose primary series; 2 primary series doses and 1 booster; or 3 primary series doses and 1 booster]. The other 28% of subjects received patterns of Hib vaccination not recommended by WHO. Considering protection from Hib disease as receipt of a WHO-recommended Hib vaccine schedule, 29% of subjects could be considered protected after 12 months of age, 52% could be considered protected during infancy and beyond, and 19% could be considered to not have been protected adequately, despite being vaccinated. Conclusions: Coverage with Hib vaccine was low. There were significant differences between WHO recommendations and actual patterns of use of Hib vaccine, with half of vaccine recipients receiving no protection during infancy and one fifth receiving non-protective Hib vaccination patterns. Inclusion of Hib vaccine into China's EPI system, which provides vaccine at no charge to parents and makes specific vaccination schedule standards, has potential to make more effective use of Hib vaccine.

Is Pneumonia Among Children in Developing Countries a Different Disease From the 1 Among Patients in the Same Age Group in Developed Countries?

Is Pneumonia Among Children in Developing Countries a Different Disease From the 1 Among Patients in the Same Age Group in Developed Countries?

Haemophilus influenza type b disease and vaccination in India: knowledge, attitude and practices of paediatricians.

Haemophilus influenza type b (Hib) causes significant morbidity and mortality among young children in India. Hib vaccines are safe and efficacious; nevertheless, their introduction to India's national immunization programme has been hindered by resistance from certain sectors of academia and civil society. We aimed to ascertain the attitudes and perceptions of Indian paediatricians towards Hib disease and vaccination. A cross-sectional survey of knowledge, attitude and practices on Hib and vaccines was undertaken among 1000 Indian paediatricians who attended 49 th National Conference of Indian Academy of Pediatrics in 2012 through use of a 21-point questionnaire. 927 (93%) paediatricians completed the survey. 643 (69%) responded that Hib is a common disease in India. 788 (85%) reported prescribing Hib vaccine to their patients and 453 (49%) had done so for the past 5-15 years. Hib vaccine was used in combination with other vaccines by 814 (88%) of the participants. 764 (82%) respondents thought Hib vaccine effective while 750 (81%) thought it to be safe. Fever, pain and redness were the most frequently reported post vaccination side-effects. 445 (48%) paediatricians ranked universal use of Hib vaccine in the national immunization programme as the most important strategy to prevent and control Hib disease in India. The excellent profile as reported by a large number of paediatricians from throughout India further strengthens evidence to support expanded use of currently available Hib vaccines. These findings should encourage the Government of India to initiate mass use of this vaccine nationwide.

Vaccination with Haemophilus influenzae type b conjugate vaccine reduces bacterial meningitis in Morocco

Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia and can be prevented by Hib vaccine. We conducted a vaccine impact evaluation to support continued use of Hib vaccine in Morocco following introduction in 2007. Bacterial meningitis surveillance data from 2004 to 2009 were obtained from 11 sentinel hospitals located in eight provinces and one prefecture in Morocco to examine Hi meningitis reporting for cases aged <5 years. We defined the years of 2004-2006 as the pre-vaccine period and 2008-2009 as the post-vaccine period and compared the mean annual number of confirmed Hi meningitis cases for these time periods using a Chi-square test. We calculated the minimum incidence of Hi meningitis during the evaluation period in Grand Casa Prefecture, where the catchment population could be estimated. From 2004 to 2009, 1844 suspected meningitis case-patients aged <5 years were reported; 354 (19.2%) were confirmed with bacterial meningitis, including 105 (29.7%) Hi cases. The mean annual number of confirmed Hi meningitis cases decreased by 75%, from 24 in the pre-vaccine period to 6 during the post-vaccine period (p<0.001). Assuming Hi cases with unknown age were <5 years of age, the estimated minimum incidence of confirmed Hi meningitis in Grand Casa Prefecture decreased by 93%, from 15 cases per 100,000 children in the pre-vaccine period to 1 case per 100,000 children in the post-vaccine period. Hib vaccine introduction likely significantly reduced the occurrence of Hi meningitis among children aged <5 years at the 11 sentinel hospitals included in this evaluation in Morocco, suggesting that continued use of Hib vaccine in Morocco would be beneficial.

Ten years of Hib vaccination in Italy: Prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance

The introduction of Haemophilus influenzae type b (Hib) conjugate vaccines has greatly reduced the incidence of invasive Hib disease. However, concern exists about the possible emergence of “strain replacement”. We report the epidemiology and characterization of isolates from invasive H. influenzae disease in Italy through 2007–2009, 10 years after Hib vaccination was introduced. Invasive H. influenzae disease cases were detected through the National Surveillance of Invasive Bacterial Disease. Seventy-eight H. influenzae strains were serotyped and tested for antimicrobial susceptibility. Genetic basis of resistance to β-lactams was investigated. The annual incidence of invasive H. influenzae infection was 0.06/100,000 in 2007, 0.08/100,000 in 2008 and 0.09/100,000 in 2009 in all age groups. A slight increase in disease incidence has been observed in adults ≥65 years since 2007. Nonencapsulated (ncHi) predominated among H. influenzae isolates from all age groups: 61.5%, 76.0%, and 75.0% for <5, 5–64 and ≥65 years, respectively. Although ncHi mainly caused bacteremia, meningitis due to ncHi increased in comparison with previous data (38.6% in 2007–2009 vs. 26.2% 1997–2002). Prevalence of encapsulated non-Hib strains grew significantly (4.1% in 1997–2002 vs.16.7% in 2007–2009; p < 0.001), although they remained rare. Resistance to ampicillin mediated by β-lactamase declined, but that due to altered penicillin-binding protein 3 increased. In conclusion, routine use of Hib vaccines produced both a drastic decrease in the number of invasive H. influenzae cases and epidemiological changes in disease. Overall, pediatric H. influenzae disease has become less common whereas there has been a slight increase of disease in the elderly. A marked change in the predominant serotype from Hib to ncHi has occurred. Changes in the H. influenzae population moderately affected antibiotic resistance trends.

Global use of Haemophilus influenzae type b conjugate vaccine

Haemophilus influenzae type b (Hib) conjugate vaccines have been underutilized globally. We report progress in global use of Hib vaccines included in national immunization schedules. The number of countries using Hib vaccine increased from 89/193 (46%) in 2004 to 158/193 (82%) by the end of 2009. The increase was greatest among low-income countries eligible for financial support from the GAVI Alliance [13/75 (17%) in 2004, 60/72 (83%) by the end of 2009], and can be attributed to various factors. Additional efforts are still needed to increase vaccine adoption in lower middle income countries [20/31 (65%) by the end of 2009].

Supporting new vaccine introduction decisions: Lessons learned from the Hib Initiative experience

The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines.

The Elimination of Haemophilus influenzae type b Meningitis Following Conjugate Vaccine Introduction in Senegal

Senegal introduced routine infant Haemophilus influenzae type b (Hib) conjugate vaccine during 2005. We evaluated acute bacterial meningitis surveillance data among children 0 to 59 months of age collected during January 2003 to September 2007 at the major pediatric referral hospital in the Dakar Region of Senegal. Hib vaccine effectiveness was assessed using a case-control design. A total of 1749 children with suspected bacterial meningitis were included in the current study of whom 142 (8%) had Hib identified. Among children less than age 1 year, the average annual Hib meningitis incidence decreased from 22 to 47 per 100,000 during 2003-2005 to 1.4 per 100,000 during 2007, while pneumococcal meningitis incidence remained stable. Before vaccine introduction, calculated incidences varied over 4-fold between districts within the Dakar Region for the years 2003 to 2005. Following use of Hib vaccine, pneumococcus has now become the most common etiology of pediatric acute bacterial meningitis in Dakar region. Senegal successfully implemented Hib conjugate vaccine into their routine infant immunization program with a resultant near elimination of Hib meningitis burden.

Knowledge of Interim Recommendations and Use of Hib Vaccine During Vaccine Shortages

The goals were to determine among pediatricians and family physicians (1) knowledge of interim recommendations regarding Haemophilus influenzae type b (Hib) vaccine administration, (2) current practices, and (3) factors associated with nonadherence. An Internet-based survey was conducted in April 2008 among national samples. Response rates were 68% (220 of 325 physicians) among pediatricians and 51% (153 of 302 physicians) among family physicians. Seventy-three percent of pediatricians and 45% of family medicine physicians reported insufficient Hib vaccine supplies, and 22% to 24% reported having to defer doses for infants 2 to 6 months of age > or =10% of the time. Ninety-eight percent of pediatricians and 81% of family physicians were aware of the interim recommendations (P < or = .0001), and virtually all knew that the booster dose should be deferred; however, 22% of pediatricians and 33% of family medicine physicians reported not deferring this dose. Physicians in both specialties were less likely to adhere to recommendations to defer in this age group if they thought that their practice had sufficient vaccine supplies (pediatricians, odds ratio: 0.01 [95% confidence interval: 0.003-0.03]; family medicine physicians, odds ratio: 0.10 [95% confidence interval: 0.03-0.33]). Family medicine physicians were less likely to adhere to recommendations if they had not heard about the interim recommendations (odds ratio: 0.04 [95% confidence interval: 0.01-0.21]). Most primary care physicians experienced Hib vaccine shortages, and many have had to defer doses for 2- to 6-month-old children. Most are knowledgeable regarding interim recommendations, but one-fifth to one-third reported nonadherence.

Foresight in medicine: current challenges with Haemophilus influenzae type b conjugate vaccines

An effective vaccine to prevent invasive infections caused by Haemophilus influenzae type b (Hib) bacteria has been available for more than 20 years. Hib conjugate vaccine is safe, efficacious and easy to use, and its cost-benefit ratio is high both in industrialized as well as in developing countries. In spite of this, WHO estimates that every year approximately 8 million children contract life-threatening Haemophilus infections, especially meningitis or severe pneumonia. If we want to take seriously the Millenium Development Goal of reducing the mortality of under 5-year-old children by two-thirds before the year 2015, an effective means to contribute to this would be more efficient use of Hib vaccines.

Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates

Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities. We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years. We calculated that Hib caused about 8.13 million serious illnesses worldwide in 2000 (uncertainty range 7.33-13.2 million). We estimated that Hib caused 371,000 deaths (247,000-527,000) in children aged 1-59 months, of which 8100 (5600-10,000) were in HIV-positive and 363,000 (242,000-517,000) in HIV-negative children. Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality. GAVI Alliance and the Vaccine Fund.

Acute bacterial meningitis among children under 5 years of age in Oman: a retrospective study during 2000-2005

During the last two decades, significant changes have taken place in the epidemiology of meningitis, especially due to the global availability and expanding use of Hib vaccines. The introduction of conjugate Hib vaccine in the Expanded Programme of Immunization (EPI) in Oman and recent availability of meningococcal vaccines against serogroups A and C plus the introduction of pneumococcal heptavalent conjugate vaccine are expected to influence the epidemiology of the disease in the country. We conducted this periodic review of acute bacterial meningitis in children younger than five years of age in Oman from January 2000 to December 2005 to reflect changes in the epidemiological pattern of these pathogens. Retrospective analysis of all cases of acute bacterial meningitis in children younger than five years of age reported to the Department of Communicable Diseases Surveillance and Control, Ministry of Health, Oman. There were 344 cases of meningitis due to suspected bacterial etiologies reported in children younger than 5 years of age. Although Haemophilus influenzae 76 (22%) was the most common pathogen identified during the study period, the incidence of meningitis due to Haemophilus influenzae has been dramatically reduced since the introduction of conjugate Hib vaccination in Oman in October 2001. Streptococcus pneumoniae 53 (15%) and Neisseria meningitidis 37 (11%) were the next two leading agents of meningitis respectively. In one hundred seventy four (52%) cases of presumptive bacterial meningitis, the etiologic organism remains unidentified. The peak occurrence of meningitis was in young children younger than one year old. The total male to female ratio was 1.4:1 and the case fatality rate (7 deaths) was 2%. With the introduction of Hib vaccine in Oman in October 2001, the absolute number of cases due to Haemophilus influenzae significantly declined over the years. The incidence of meningitis due to other pathogens such as S. pneumoniae and N. meningitidis remains steady. There is significant need to improve laboratory methods of bacterial detection and identification, which will help to formulate better antibiotic policies and strengthen control measures through newly introduced vaccines in Oman.

Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case–control study

To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda. Case-control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case-patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables. We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV-negative, had received >/=2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92-100%] and 96% (95% CI 80-100%) when cases were compared with neighbourhood and hospital controls, respectively. In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality.

Use of vaccine trials to estimate burden of disease.

Vaccine trials, the most informative way of determining the efficacy of a vaccine, can also provide valuable information about the burden of disease. The burden of Haemophilus influenzae type b (Hib) remains a major barrier to the use of Hib vaccines, especially in Asia. Recent studies in Indonesia and Bangladesh have used vaccine-trial designs, with known effective vaccines, to estimate the vaccine-preventable burden of Hib disease in those communities. New vaccines against pneumonia and diarrhoeal diseases are usually directed at only one of various causes of the syndrome. In the case of pneumonia, it is very difficult to determine the aetiology in most cases, so the vaccine trial offers a means of determining the burden of vaccine-preventable diseases. This is particularly important for pneumococcal vaccines as serotype replacement may reduce the effectiveness of the vaccines in the field. This approach would underestimate disease burden if vaccines were found to have an impact on syndromes other than those against which they are directed, and might lead to errors in estimation if there were erroneous assumptions about the efficacy of the vaccine against the condition under investigation.

H. influenzae type b (Hib) vaccine--controversies.

Hib vaccine is the 8th vaccine knocking at the door to be included in the EPI the world over. However there are some controversies that need to be addressed, especially when it comes to use of this vaccine in India. It is difficult to culture Hib unless one uses sheep blood enriched media for culture. There is a lack of good community based data on Hib burden in India. This makes many feel that Hib is rare in India. However this is not true. There are many studies that have looked at this closely. Hib is a common cause of meningitis and pneumonitis in children less than 5 years old in India. There is wide spread problem of multi-drug resistance by Hib in India. Mortality of meningitis is as high as 100% if third generation cephalosporins are not used in time. Of the survivors of meningitis, 60% develop long-term sequelae. Hib vaccine is very effective and can lead to 99% reduction with mass vaccination in just 2-3 years. It is also a very safe vaccine. Of the conjugated vaccines available in India all are equally effective and safe and there is nothing to choose one over the other. There is a need to give a booster dose at 15-18 months of age. Even UK, which never gave the booster dose, is seriously thinking of changing their practice and give a booster dose. Lastly the combination vaccines of Hib with IPV, DPwT/DPaT, and Hepatitis B are safe and effective and should be encouraged to improve the compliance. The use of Hib vaccine is recommended in India, for those who can afford the vaccine.

Characterization of haemophilus influenzae isolated from invasive disease in Brazil from 1990 to 1999.

The Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in the National Immunization Program in Brazil in the second half of 1999. A retrospective analysis on serotypes, biotypes, and antimicrobial resistance of Hi invasive strains obtained through Hi survey was conducted to document the characteristics of this pathogenic agent during a decade prior the use of Hib vaccine. A total 3,204 strains from 1990 to 1999 were studied, being 88.2% isolated from cerebrospinal fluid, 10.7% from blood, and 1.1% from pleural fluid. The rate of 90.9% of strains was obtained from children up to 4 years old, and the age group >6 months old to 1 year was the higher risk to Hi infection. Type b was, by far, the most common type (97.8%), followed in frequency by type a (0.5%); only 1.5% was a nontypable strain. Biotypes I and II accounted for 97.8% of isolates. Resistance to ampicillin (AM) and chloramphenicol (CO) was detected at rates of 18.1% and 19.1%, respectively, whereas simultaneous resistance to AM and CO was identified in 13.9% of strains. Total concordance was found between AM resistance and beta-lactamase production. No strain showed resistance to ceftriaxone and rifampicin. In conclusion, the data generated through this laboratory-based surveillance should serve as a reference for assessing the impact of Hib vaccination and to detect changes on the pattern of Hi diseases in the country.

Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study.

To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria. From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity. During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins. On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.