AJTMH Transactions of the Royal Society of Tropical Medicine and Hygiene
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am. J. Trop. Med. Hyg., 74(3), 2006, pp. 509-515
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ANH, D. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ANH, D. D.
Related Collections
Right arrow Bacterial Infection
Right arrow Epidemiology

HAEMOPHILUS INFLUENZAE TYPE B MENINGITIS AMONG CHILDREN IN HANOI, VIETNAM: EPIDEMIOLOGIC PATTERNS AND ESTIMATES OF H. INFLUENZAE TYPE B DISEASE BURDEN

DANG D. ANH, PAUL E. KILGORE*, WILLIAM A. KENNEDY, BATMUNKH NYAMBAT, HOANG T. LONG, LUIS JODAR, JOHN D. CLEMENS, JOEL I. WARD THE VIETNAM INVASIVE BACTERIAL DISEASE SURVEILLANCE NETWORK{dagger}
Department of Bacteriology, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam; Division of Translational Research, International Vaccine Institute, Seoul, Republic of Korea; Center for Vaccine Research, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
From March 2000 to February 2002, a population-based study of Haemophilus influenzae type b (Hib) meningitis was conducted among children less than five years of age in Hanoi, Vietnam. Children with suspected bacterial meningitis were referred to hospitals and each patient underwent standardized clinical examination and microbiologic testing. In Hanoi, 580 children were evaluated for bacterial meningitis and 23 (4%) had confirmed or probable Hib meningitis. The incidence of all Hib meningitis was 12/100,000 child-years less than five years of age and 26/100,000 child-years less than two years of age. Nationally, an estimated 1,005 children less than five years of age are hospitalized for Hib meningitis and 5,107 are hospitalized for Hib pneumonia. Among children with Hib meningitis, at least 100 will develop severe neurologic sequelae and 40 will die. These data suggest there is a substantial burden of Hib disease in Vietnam. National leaders will be provided with these data to facilitate development of national vaccination policies for children in Vietnam.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Globally, prior to introduction of conjugate vaccines directed against Haemophilus influenzae type b (Hib), there were an estimated 300,000–400,000 deaths and 2.2 million cases in children each year due to Hib disease.1,2 After the introduction of conjugate Hib vaccines into national childhood immunization programs, the decrease in incidence of Hib disease in children in several countries has been well-documented.3–7 In 1999, the Global Alliance for Vaccines and Immunizations (GAVI) was launched to support improvement of immunization programs in developing countries. GAVI has also recognized that a major barrier to the rational introduction of Hib vaccine has been the limited availability of credible disease burden data among children.

In Vietnam, Tran and others in Ho Chi Minh City showed that Hib caused 53% of culture-proven bacterial meningitis in hospitalized children.8 In the northern region of Vietnam, a community-based survey showed that Hib was carried by 39% of the children and that 68% of the Hib isolates were resistant to at least one antibiotic.9 These data have suggested that the burden of disease was substantial, but few data are available to understand the incidence of Hib meningitis and the consequent neurologic sequelae. Despite these data, however, no population-based incidence rates of Hib meningitis have been available in Vietnam. To address the need for this information, we conducted a population-based study of bacterial meningitis in Hanoi, Vietnam.


METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study population. The study population consisted of 94,529 children ≤ 59 months of age residing in the seven urban district of Hanoi, Vietnam.10 In this population, children with suspected meningitis were referred to one of three central hospitals in Hanoi: 1) National Pediatric Hospital, 2) St. Paul Hospital, and 3) Bach Mai Hospital. Because these hospitals are major tertiary care centers for children in the northern region of Vietnam, they also serve residents in the five outlying districts of Hanoi province (population = 1.2 million people). The study was reviewed and approved by the Institutional Review Board of the Research and Educational Institute at Harbor–UCLA Medical Center and by the Ethical Research Committee of the National Institute of Hygiene and Epidemiology (NIHE), (Hanoi, Vietnam). Informed consent for each subjects’ participation was verbally obtained from each parent. Training workshops were conducted to provide standardized procedures for the referral of children with signs and symptoms of meningitis as well as the clinical and laboratory evaluations.

Clinical evaluation of patients. From March 4, 2000 through March 3, 2002, active surveillance for meningitis in children ≤ 59 months of age was established in Hanoi. Children residing outside the city in suburban areas of Hanoi and rural northern provinces were detected by passive surveillance. These children were evaluated for meningitis if they met the same referral and age criteria used for children in Hanoi. Children ≤ 59 months of age were referred for evaluation if they had a body temperature > 37.5°C (axillary) or > 38.0°C (orally) and had at least one of the following signs/ symptoms: headache, bulging (tense) fontanelle, nuchal rigidity, forceful vomiting, or mental status changes including irritability, confusion, lethargy, or coma. Children were admitted to inpatient pediatric wards after the collection of blood and cerebrospinal fluid (CSF) to measure indices of inflammation (e.g., CSF glucose level) and perform bacterial culture testing. Medical histories and demographic data were obtained in interviews with parents or guardians, and laboratory data were collected using standardized case report forms and laboratory procedures. Neurologic sequelae were assessed clinically at the time of hospital discharge and were defined as any cranial nerve (e.g., hearing loss), motor (e.g., paralysis), or cognitive (e.g., vegetative state) deficit at the time of hospital discharge.

Case definitions. Abnormal CSF was defined by the presence of one or more of the following: 1) visibly turbid CSF, 2) CSF white blood cell count (WBC) > 30 cells/mm3 for neonates ≤ 1 month of age and > 10 cells/mm3 for older infants and children), 3) CSF neutrophils > 70% of total CSF WBCs, 4) CSF protein concentration > 170 mg/dL for neonates ≤ 1 month of age or > 75 mg/dL for older infants and children, or 5) CSF glucose concentration < 40 mg/dL.11,12 The following case definitions were used: 1) confirmed Hib meningitis: growth of Hib in CSF culture or abnormal CSF and growth of Hib in a blood culture; 2) confirmed bacterial meningitis: growth of a bacterial pathogen in CSF or abnormal CSF and growth of a bacterial pathogen in a blood culture; 3) probable Hib meningitis: presence of abnormal CSF findings and identification of Hib in CSF by Gram stain or detection by latex agglutination antigen (LA) or DNA polymerase chain reaction (PCR) tests; 4) suspected bacterial meningitis: presence of abnormal CSF with no identifiable bacterial pathogen by culture or other testing; 5) probable bacterial meningitis: according to the World Health Organization (WHO) a probable bacterial meningitis case requires a child to have one or more signs or symptoms of meningitis and either a CSF with turbid appearance or CSF protein > 100 mg/dL or glucose < 40 mg/dL or WBCs > 100 cells/mm3 with > 80% neutrophils and no identifiable bacterial pathogen.13

Laboratory evaluations. The CSF was sent to the laboratory within one hour of collection and a Gram stain was performed on uncentrifuged CSF. Two drops each of CSF were streaked onto commercially prepared blood and chocolate agar media (BBL®; Becton Dickinson, Franklin Lakes, NJ). Residual CSF was inoculated into 5% Fildes broth.14–16 The CSF broth was routinely sub-cultured after 24 hours, 72 hours, and 7 days of incubation. Blood was inoculated into BACTEC® Peds Plus®/F bottles (Becton Dickinson) with growth detected using either an automated blood culture system or after routine subculture at one, three, and seven days of incubation. Bacterial identification was performed using standard microbiologic criteria.15 External proficiency testing was performed periodically throughout the study to ensure accuracy in bacterial growth on study media and identification.17 Abnormal CSF was tested for the presence of Hib, S. pneumoniae, and Neisseria meningitidis capsular polysaccharides by latex agglutination (Slidex Meningite®; BioMerieux; Marcy l’Etoile, France). The PCR was performed using a PCR enzyme-linked immunosorbent assay method to detect H. influenzae bexA gene and S. pneumoniae ply gene DNA using previously published methods.16,18

Data management and statistical analysis. Case report forms were transmitted to the study data management center and entered into a computerized database at the NIHE in Hanoi. Study case report forms were compared with available data in hospital medical charts, and study databases were regularly inspected for accuracy of recorded data. Study investigators conducted microbiology laboratory record audits by comparing logbook (blood and CSF specimen records, bacterial culture records) information with study laboratory reports to identify missed meningitis cases.

Categoric comparisons were performed with the chi-square test. The Fisher exact test was used in analysis with expected cell sizes less than five (SAS® statistical software version 8.1; SAS, Inc., Cary, NC). Comparison of dimensional variables was oerformed with Student’s t-test or the Mann-Whitney U test when data were not normally distributed. Test statistics were evaluated with a significance level of P < 0.05. Incidence rates were calculated using person-time denominators that incorporated the two-year period of prospective surveillance and 1999 census data for children ≤ 59 months of age in Hanoi.10 Ninety-five percent confidence intervals (CIs) for incidence rates were calculated by the Wilson score method.19 The estimated national burden of Hib meningitis (hospitalizations and deaths) was calculated directly from the Hib meningitis incidence and case-fatality rate (CFR) determined in this study. To estimate the incidence of Hib pneumonia, we assumed that the frequency of Hib pneumonia hospitalizations was five times the number of Hib meningitis hospitalizations.20 This assumption, which was used in the WHO Rapid Assessment Tool for Hib disease, is based on the ratio of Hib pneumonia to Hib meningitis cases observed in two studies that described the burden of Hib pneumonia and Hib meningitis.21,22


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Characteristics of children with meningitis. Between March 4, 2000 and March 3, 2002, a total of 3,407 children from Hanoi, suburban Hanoi, and other northern provinces were prospectively evaluated for bacterial meningitis. Of these children, 580 lived in the Hanoi active surveillance study population (Table 1Go). In Hanoi, 47% of the children evaluated were ≤ 11 months of age, 24% were neonates (< 1 month of age), and 15% were 1–6 months of age. From parent-reported data, only 3 (0.5%) of the 580 children evaluated for bacterial meningitis in this study had received conjugate Hib vaccine (0 of the 3 had confirmed Hib meningitis or probable Hib meningitis) and 102 (18%) used antibiotics prior to hospitalization.


View this table:
[in this window]
[in a new window]
 
TABLE 1
Demographic characteristics and incidence of bacterial meningitis (suspected and probable) and meningitis due to Haemophilus influenzae type b (Hib) (confirmed and probable) in children ≤ 59 months of age, Hanoi, Vietnam, March 4, 2000–March 3, 2002*
 
Suspected and probable bacterial meningitis. In the Hanoi active surveillance population (Table 1Go) among children ≤ 59 months of age, suspected bacterial meningitis was found in 251 (43%) of the 580 children evaluated. The annual incidence of suspected bacterial meningitis was 133/100,000 (95% CI = 111–156). The highest age-specific incidence rates for suspected bacterial meningitis were 1,773/100,000 (95% CI = 1,199–2,615) among neonates and 199/100,000 (95% CI = 123–321) among infants 1–6 months of age. Probable bacterial meningitis was found in 166 (29%) of 580 children evaluated and the annual incidence of probable bacterial meningitis was 88/100,000 children ≤ 59 months of age (95% CI = 71–109). Age-specific incidence rates for probable bacterial meningitis were slightly lower than the corresponding age-specific incidence rates of suspected bacterial meningitis with the exception of neonates in whom the incidence was 1,954/100,000 (95% CI = 1,346–2,829) (Table 1Go). Among children living in either suburban Hanoi or rural provinces outside the Hanoi active surveillance area, 1,019 cases of probable bacterial meningitis and 1,265 cases of suspected bacterial meningitis were identified (Table 2Go).


View this table:
[in this window]
[in a new window]
 
TABLE 2
Clinical and cerebrospinal fluid (CSF) chracteristics in children ≤ 59 months of age with meningitis in Hanoi city (active surveillance area), suburban Hanoi, and other northern provinces (passive surveillance area), Vietnam, March 4, 2000–March 3, 2002*
 
Confirmed Hib and probable Hib meningitis. In the Hanoi active surveillance population, 13 children had confirmed Hib meningitis and 10 children had probable Hib meningitis (Table 1Go). All 10 children with probable Hib meningitis had CSF positive by the H. influenzae PCR, but none were positive by either CSF LA or Gram stain. For children ≤ 59 months of age, the annual total incidence of confirmed Hib meningitis plus probable Hib meningitis was 12/100,000 (95% CI = 7–22) and the incidence for confirmed Hib meningitis alone was 7/100,000 (95% CI = 3–15). For children ≤ 23 months of age, the annual total incidence rate of confirmed Hib meningitis plus probable Hib meningitis was 26/100,000 (95% CI = 13–51) including the 13 children with confirmed Hib meningitis (Figure 1Go). The highest age-specific rates of confirmed Hib meningitis plus probable Hib meningitis, 30/ 100,000 and 44/100,000, were found among infants 1–6 and 7–11 months of age, respectively. In children 24–60 months oaf age, no cases of confirmed Hib meningitis were identified, but 7 of the 10 children with probable Hib meningitis (CSF culture negative, H. influenzae PCR positive) were identified in this older age group.


Figure 1
View larger version (22K):
[in this window]
[in a new window]
  		    FIGURE 1. Cumulative incidence of Haemophilus influenzae type B (Hib) meningitis by age group among children ≤ 59 months of age in an active surveillance area of Hanoi, Vietnam, March 4, 2000 through March 3, 2002.

 
Among the presenting signs and symptoms of meningitis, altered mental status, nuchal rigidity, and seizure were more commonly observed among children with confirmed Hib meningitis and probable Hib meningitis compared with those having suspected bacterial meningitis (Table 2Go). Among cases determined to be confirmed Hib meningitis, probable Hib meningitis, probable bacterial meningitis, and suspected bacterial meningitis, those from suburban Hanoi or rural provinces presented with more severe disease compared with children from Hanoi. For each meningitis case category, children living in suburban Hanoi or rural provinces were also more likely to have received prior antibiotic treatment.

Other bacterial meningitis. In all surveillance areas (active and passive surveillance areas), there were 211 children ≤ 59 months of age identified with bacterial meningitis during the 24-month surveillance period. Of the 116 children with Hib meningitis, 51 had Hib isolated in both CSF and blood, 48 had Hib isolated in only CSF, and 17 children were categorized as probable Hib meningitis. Eighty percent (n = 93) of the confirmed Hib meningitis and probable Hib meningitis cases were identified from suburban Hanoi and other northern provinces.

Case-fatality and neurologic sequelae. In all areas of surveillance, the overall CFR in children with confirmed Hib and probable Hib meningitis was 4% (n = 5) (Table 3Go). All Hib meningitis–associated deaths occurred in children from suburban Hanoi and rural provinces; no children died of Hib meningitis in Hanoi. Among children from Hanoi, suburban Hanoi, and rural provinces, neurologic sequelae were observed in 12 (10%) of 116 children with either confirmed Hib meningitis or probable Hib meningitis. Among these 12 children with Hib-associated sequelae, hydrocephalus (n = 4), developmental delay (n = 2), limb paralysis (n = 2), seizure disorder (n = 4), and vegetative state (n = 1) were identified.


View this table:
[in this window]
[in a new window]
 
TABLE 3
Neurologic sequelae and deaths among children ≤ 59 months of age with meningitis in Hanoi, suburban Hanoi, and rural northern provinces, Vietnam, March 4, 2000–March 3, 2002*
 
Other invasive disease. Streptococcus pneumoniae was found among 11% (n = 28) and N. meningitidis was found in 4% (n = 10) of children with non-Hib invasive disease (bacterial isolates from normally sterile sites). In the Hanoi active surveillance population, there were three children with pneumococcal meningitis and one with pneumococcal bacteremia, giving an annual incidence rate for pneumococcal meningitis of 1.6/100,000 (95% CI = 0.4–6.9) in children ≤ 59 months of age. Using meningococcal cases (n = 5) identified in the active surveillance area of Hanoi, we found that the annual incidence rate of meningococcal meningitis was 2.6/100,000 in children ≤ 59 months of age (95% CI = 0.8–8.5), with the highest rate found in infants 7–11 months of age (21.8/100,000; 95% CI = 5.0–94.4).

Burden of Hib disease. Recent population census data show that Vietnam has 8,371,377 children ≤ 59 months of age. In addition, recent Vietnam population data report that there were 1,674,275 newborn babies in 2004. Based on the national population and Hib meningitis incidence from Hanoi, there are an estimated 1,005 hospitalizations each year for Hib meningitis with at least 40 deaths associated with Hib meningitis. Of the 1,005 children hospitalized for Hib meningitis, it is estimated that at least 100 children have severe neurologic sequelae as a result of Hib meningitis. Based on the population distribution of children ≤ 59 months of age, more than half (~553) of severe Hib meningitis cases that lead to hospitalization occur among infants. Based on expected ratio of Hib pneumonia to Hib meningitis cases, we would expect 115 cases of Hib pneumonia each year in Hanoi. Thus, the estimated incidence of Hib pneumonia among children ≤ 59 months of age was 61/100,000 (95% CI = 47–79) during the study period. Nationally, we estimate that there are at least 5,107 hospitalizations for Hib pneumonia each year among children ≤ 59 months of age.


DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In this prospective, population-based study of acute bacterial meningitis, Hib was the most common bacterial etiology among children in Hanoi, suburban districts of Hanoi, and other northern provinces of Vietnam. Haemophilus influenzae type B was responsible for 56% and 49% of culture- or PCR-positive bacterial meningitis cases in Hanoi, suburban Hanoi, and rural provinces, respectively. In Hanoi, the total Hib meningitis incidence (confirmed Hib meningitis and probable Hib meningitis) was 12/100,000 in children ≤ 59 months of age. In children ≤ 59 months of age, probable bacterial meningitis produced a sizable disease burden with an annual incidence rate of 88/100,000 children. All Hib meningitis-associated deaths were among children living outside Hanoi in either suburban Hanoi districts or rural provinces (CFR = 5% among 93 children with confirmed or probable Hib meningitis).

Our study has some limitations. First, we limited standard clinical evaluations and obtained cultures from children with meningitis or sepsis and we did not systematically evaluate and enroll children with cellulitis, pneumonia, epiglottitis, septic arthritis, or osteomyelitis. Second, the approach for estimating the incidence of Hib pneumonia is based on assumptions described in the Hib Rapid Disease Burden Assessment tool developed by a WHO expert panel. In this algorithm, it is assumed that five cases of serious Hib pneumonia occur for every one case of Hib meningitis, but we recognize that there may be some variations in this ratio by country or region. Third, although considerable efforts were made to use surveillance and laboratory methods that would enhance detection of meningitis, 34% of the children in Hanoi as well as suburban and rural Hanoi who were diagnosed with confirmed Hib meningitis and probable Hib meningitis had received antibiotics prior to hospital evaluation. In a survey from a community near Hanoi, Vietnam, Larsson and others noted that 91% of children with acute respiratory infection received treatment with antibiotics.9 Thus, in our study, the antibiotic usage information from parents/guardians who sought care likely underestimates the actual number of children pretreated with antibiotics because parents were instructed to report treatment as unknown if they could not precisely recall the use of an antibiotic. Also, in our study, a high proportion of children with abnormal CSF consistent with suspected or probable bacterial meningitis also had negative CSF Hib cultures and PCR test results. These results are consistent with previous studies showing that CSF in patients with antibiotic treatment may show abnormal test results even after cultures and/or antigen test results have become negative.23,24 Finally, our study detected patients who were sick enough for referral to hospitals. Patients (including those with fever as their only symptom) having less severe disease would have been more likely to receive immediate antimicrobial therapy at commune health centers or private clinics under national guidelines based on the Integrated Management of Childhood Illness protocols for Vietnam.25 This may have prevented invasive Hib disease from being detected during surveillance.

The incidence rates of Hib meningitis observed in this study were in the lower range of incidence rates for Hib meningitis found globally. This range of Hib incidence includes some of the highest observed rates from indigenous populations in the United States (409/100,000 children < 5 years of age)26 and Australia (150/100,000 children < 5 years of age)27 to the lowest rates observed in several Asian countries including Thailand (4/100,000 children < 5 years of age), the Republic of Korea (6/100,000), and China (Hefei, 10/100,000).16,28,29 The total confirmed Hib meningitis and probable Hib meningitis incidence rates found in Hanoi are similar to those found in European countries such as Austria (9/100,000 children < 5 years of age), Spain (6/100,000), and Greece (8/100,000).30–32

The higher incidence rate for Hib meningitis that we observed in Hanoi compared with data from other population-based studies in Asia may be due to at least two key features of our study design.33 First, study investigators provided laboratory training, supervision, and enhanced microbiologic diagnostic capacity in each study hospital. This strengthened capacity was demonstrated in data from the National Pediatric Hospital where confirmed Hib meningitis was detected nine times more often during the study period compared with the two-year period prior to our surveillance study (90 cases versus 10 cases). Our study also provided standardized microbiology methods as well as commercially prepared bacterial culture media containing IsoVitaleX® (BBL Microbiology Systems, Cockeysville, MD) for Haemophilus influenzae growth enhancement and reagents for bacterial identification.

A second feature of our study design was the inclusion of CSF testing by PCR that increased our detection of Hib meningitis by 77% compared with the use of bacterial culture alone. The added value of PCR was underscored by the results from older children 24–59 months of age in whom 7 of the 10 total probable Hib meningitis cases who were detected by CSF H. influenzae PCR testing. Although PCR detected several additional cases of Hib meningitis, no additional gains in Hib meningitis case detection occurred using latex agglutination Hib antigen detection. This finding may be due to a number of factors, including the reported lower sensitivity (86%) of latex agglutination antigen detection relative to bacterial culture.34,35 One study suggested that Hib latex agglutination may require ≤ 1,000 bacteria/mL of CSF to yield a positive test result.36

The present study provides evidence from population-based surveillance that Hib is the most common cause of bacterial meningitis among Vietnamese children living in urban and rural settings with high incidence rates observed in children < 24 months of age. Furthermore, there are an estimated 6,111 cases of severe Hib disease among Vietnamese children every year including 1,005 cases of Hib meningitis and 5,107 due to Hib pneumonia. These data will be provided to national decision-makers to help inform decisions regarding the introduction of conjugate Hib vaccine into the routine national childhood immunization schedule. Future Hib-related activities in Vietnam will focus on the development of a national Hib reference laboratory capacity and a reporting system for identifying persons with culture-confirmed invasive Hib disease.

Received September 28, 2005. Accepted for publication October 20, 2005.

Acknowledgments: We thank Professor Dang Duc Trach, Duc Thang Bui, and Dr. Dinh Thiem Vu for their support in development of the study protocol and field site; Dr. Hoa Thi Lan Nguyen, Dr. Cong Khanh Nguyen, Anh Thi Hien Nguyen, Dr. Anh Thi Ngan Nguyen, Dr. Huong Thu Vu, Thi Tuyet Phi, and Dr. Huong Le Thanh Pham for assistance in study monitoring and technical support for surveillance; Dr. Hai Feng Hwang, Dr. Susan Partridge, Jennie Jing, Swei-Ju Chang, and Dr. Joo Yeun Kim for work in planning the study and development of study operating procedures, data forms, data entry systems, and laboratory database management; and Dr. Eunsik Park and Deok-Ryun Kim for statistical and database management consultation. We sincerely thank Professor E. Kim Mulholland, Professor Ron Dagan, Dr. Jay Wenger, and Professor Zhi Yi Xu for their counsel during development of the International Vaccine Institute multi-country Hib surveillance studies. We also thank Min Kyoung Oh for help in preparing this manuscript, Helen Kim for ethical guidance, and Kathy Murray for editorial review of this manuscript.

Financial support: This study was supported by Bill and Melinda Gates Children’s Vaccine Program at Program for Appropriate Technology in Health, GlaxoSmithKline Biologicals, Merck Vaccines, and Wyeth Vaccines. The American Committee on Clinical Tropical Medicine and Travelers’ Health (ACCTMTH) assisted with publication expenses.

Disclosure: Paul E. Kilgore is currently conducting research supported in part by GlaxoSmithKline Biological, Wyeth Vaccines, and Sanofi-Aventis. This statement is made in the interest of full disclosure and not because the author considers this to be a conflict of interest.

* Address correspondence to Paul E. Kilgore, Division of Translational Research, International Vaccine Institute, Gwanak-Ku P.O. Box 14, Seoul, Republic of Korea 151-600. E-mail: pkilgore{at}ivi.int Back

{dagger} The Vietnam Invasive Bacterial Disease Surveillance Network; National Pediatric Hospital: Cong Khanh Nguyen, Thi Thi Ngo, Thu Hang Dang, Thi Lich Bui, Thi Suu Pham, Ngoc Khanh Nguyen, Van Lam Nguyen, Thi Hoan Phung, Thi San Luong, Khanh Dung Khu, Kim Nga Nguyen, Tran Van Ung, and Nguyen Thi Linh; St. Paul Hospital: Huyen Thi Minh Nguyen, Vinh Lai Nong, Sam Thi Do, Hoa Mai Nguyen, Uong Bao Nguyen, Lam Thanh Tran, Thoa Kim Nguyen, Thao Thi Bui, Cach Thi Do, Thoa Thi Nguyen, Khanh Ngoc Nguyen, Vinh Le, Thanh Thi Ngo, Siu Thi Nguyen, Anh Thuy Nguyen, Van Bich Trang, Thanh Trung Nguyen, Nhi Y Pham Nguyen, Tang Duy Nguyen, Hanh Nha Phung, Hong Thu Nguyen, Nhan Thanh Nguyen, Long Duy Ta, Duc Van Dao, Anh Tuan Nguyen, Ngoc Hong Nguyen, Van Bich Nguyen, Dieu Thu Nguyen, Dung Thi Nguyen, Tam Thi Nguyen, Nga Thi Nguyen, Binh Thi Nguyen, Nga Phi Nguyen, Thanh Thi Le, Phuc Thi Nguyen, Lung Thi Nguyen, Tan Thi Le, Hoa Xuan Nguyen, Hoan Thi Nguyen, Thuy Thanh Nguyen, Minh Van Nguyen, Thu Minh Hoang, Lien Thi Tran, Duong Thuy Bui, Thuy Thi Nguyen, Diep Ngoc Do Pham, Nga Phuong Nguyen, Hien Phuong Le, Truong Thi Nguyen, Cam Thuy Ngo, Thinh Thi Nguyen, Thai Thi Nguyen, Tuyet Anh Luong Phan, Gian Thi Luong, Anh Hai Nguyen, Huong Thien Nguyen, Huong Thanh Nguyen, and Ngoc Thi Nguyen; Hanoi City Health Department: Quy Tran, Tien Dung Nguyen, Tien Dung Do, Van Bang Nguyen, Thuy Tai Le, Van Nam Nguyen, Xuan Quang Nguyen, Mai Phuong Doan, Nguyen Thi Lien, Khac Trieu Nguyen, Anh Tuan Le, Nguyen Duc Binh, Thi Tan Nguyen, Ming Hai Nguyen, Thau Van Nguyen, Dai Dong Nguyen, Ngoc Hung Nguyen, Ha Tien Lam, Anh Thieu Cu, Dan Thi Nguyen, Binh Quyet Dinh, Minh Ngoc Nguyen, Thi Mai Nguyen, Mai Lan Nguyen, Ngoc Bich Nguyen, Thi Thi Nguyen, Thi Xuyen Nguyen, Thi Chi Nguyen, Hai Minh Nguyen, Thi Dung Nguyen, Long Tuan Nguyen, Van Khanh Nguyen, Tho Duc Le, and Hong Xuan Doan. Back

Authors’ addresses: Dang D. Anh, Department of Bacteriology, National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hanoi, Vietnam 10,000, Telephone: 844-971-6009, Fax: 844-971-6485, E-mail: ducanhnihe{at}hn.vnn.vn. Paul E. Kilgore, Nyambat Batmunkh, Luis Jodar, and John D. Clemens, Divisional of Translational Research, International Vaccine Institute, Gwanak-Ku P.O. Box 14, Seoul, Republic of Korea, 151-600, Telephone: 822-872-2801, Fax: 822-872-2803, E-mails: pkilgore{at}ivi.int, bnyam{at}ivi.int, ljodar{at}ivi.int, and jclemens{at}ivi.int. William A. Kennedy and Joel I. Ward, UCLA Center for Vaccine Research, Liu Research Building (RB3), 1124 W. Carson Street, Torrance, CA 90502, Telephone: 310-781-3636, Fax: 310-972-2962, E-mails: wkennedy{at}uclacvr.labiomed.org and jward{at}uclacvr.labiomed.org. Hoang T. Long, National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hanoi, Vietnam 10,000, Telephone: 844-971-6009, Fax: 844-971-6485, E-mail: nihe{at}hn.vnn.vn.

Reprint requests: Paul E. Kilgore, Divisional of Translational Research, International Vaccine Institute, Gwanak-Ku P.O. Box 14, Seoul, Republic of Korea, 151-600, E-mail: pkilgore{at}ivi.int.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Jamison DT, Mosley WH, Measham AR, Bobadilla JL, 1993. Disease control priorities in developing countries. Stansfield SK, Shepard DS, eds. Acute Respiratory Infection. Second edition. New York: Oxford University Press, 67–90.
  2. Anon., 1998. Global programme for vaccines and immunization (GPV). The WHO position paper on Haemophilus influenzae type b conjugate vaccines. Wkly Epidemiol Rec 73: 64–68.[Medline]
  3. de la Hoz F, Higuera AB, Di Fabio JL, Luna M, Naranjo AG, de lL V, Pastor D, Hall AJ, 2004. Effectiveness of Haemophilus influenzae type b vaccination against bacterial pneumonia in Colombia. Vaccine 23: 36–42.[ISI][Medline]
  4. Martin M, Casellas JM, Madhi SA, Urquhart TJ, Delport SD, Ferrero F, Chamany S, Dayan GH, Rose CE, Levine OS, Klugman KP, Feikin DR, 2004. Impact of Haemophilus influenzae type b conjugate vaccine in South Africa and Argentina. Pediatr Infect Dis J 23: 842–847.[ISI][Medline]
  5. McVernon J, Howard AJ, Slack MP, Ramsay ME, 2004. Long-term impact of vaccination on Haemophilus influenzae type b (Hib) carriage in the United Kingdom. Epidemiol Infect 132: 765–767.[Medline]
  6. Hviid A, Melbye M, 2004. Impact of routine vaccination with a conjugate Haemophilus influenzae type b vaccine. Vaccine 22: 378–382.[ISI][Medline]
  7. Peltola H, Aavitsland P, Hansen KG, Jonsdottir KE, Nokleby H, Romanus V, 1999. Perspective: a five-country analysis of the impact of four different Haemophilus influenzae type b conjugates and vaccination strategies in Scandinavia. J Infect Dis 179: 223–229.[ISI][Medline]
  8. Tran TT, Le QT, Tran TN, Nguyen NT, Pedersen FK, Schlumberger M, 1998. The etiology of bacterial pneumonia and meningitis in Vietnam. Pediatr Infect Dis J 17: S192–S194.[ISI][Medline]
  9. Larsson M, Kronvall G, Chuc NT, Karlsson I, Lager F, Hanh HD, Tomson G, Falkenberg T, 2000. Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community. Trop Med Int Health 5: 711–721.[ISI][Medline]
  10. Central Census Steering Committee, 2000. 1999 Population and Housing Census: Sample Results. Hanoi, Vietnam.
  11. Sarff LD, Platt LH, McCracken GH Jr, 1976. Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis. J Pediatr 88: 473–477.[ISI][Medline]
  12. Oski FA, 1999. Laboratory values. Oski’s Pediatrics: Principles and Practice. Third edition. New York: Lippincott Williams and Wilkins, 2216–2224.
  13. Levine O, Schuchat A, Schwartz B, Wenger JD, Elliott J, 1996. Generic Protocol for Population-Based Surveillance of Haemophilus influenzae type b. Geneva: World Health Organization. WHO/VRD/GEN/95.05.
  14. Daly J, Seskin KC, Pezzlo M, 1992. Processing and interpretation of cerebrospinal fluid. Isenberg HD, ed. Clinical Microbiology Procedures Handbook. First edition. Washington, DC: American Society for Microbiology Press, 67–72.
  15. Murray PR, Baron EJ, Pfaller MA, Tenover PC, Yolken RH, 1995. Manual of Clinical Microbiology. Sixth edition. Washington, DC: American Society for Microbiology Press, 301–561.
  16. Kim JS, Jang YT, Kim JD, Park TH, Park JM, Kilgore PE, Kennedy WA, Park E, Nyambat B, Kim DR, Hwang PH, Kim SJ, Eun SH, Lee HS, Cho JH, Kim YS, Chang SJ, Huang HF, Clemens JD, Ward JI, 2004. Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children. Vaccine 22: 3952–3962.[ISI][Medline]
  17. National Committee for Clinical Laboratory Standards, 2000. NCCLS Quality Manual. Wayne, PA: NCCLS.
  18. Salo P, Ortqvist A, Leinonen M, 1995. Diagnosis of bacteremic pneumococcal pneumonia by amplification of pneumolysin gene fragment in serum. J Infect Dis 171: 479–482.[ISI][Medline]
  19. Newcombe RG, 1998. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med 17: 873–890.[ISI][Medline]
  20. World Health Organization, 2004. Estimating the Local Burden of Haemophilus influenzae Type b (Hib) Disease Preventable by Vaccination. A Rapid Assessment Tool. Geneva: World Health Organization. Wor(WHO/V&B/01.27), 1–67.
  21. Mulholland K, Hilton S, Adegbola R, Usen S, Oparaugo A, Omosigho C, Weber M, Palmer A, Schneider G, Jobe K, Lahai G, Jaffar S, Secka O, Lin K, Ethevenaux C, Greenwood B, 1997. Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants. Lancet 349: 1191–1197.[ISI][Medline]
  22. Levine OS, Lagos R, Munoz A, Villaroel J, Alvarez AM, Abrego P, Levine MM, 1999. Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b. Pediatr Infect Dis J 18: 1060–1064.[ISI][Medline]
  23. Kanegaye JT, Soliemanzadeh P, Bradley JS, 2001. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 108: 1169–1174.[Abstract/Free Full Text]
  24. Stuertz K, Merx I, Eiffert H, Schmutzhard E, Mader M, Nau R, 1998. Enzyme immunoassay detecting teichoic and lipoteichoic acids versus cerebrospinal fluid culture and latex agglutination for diagnosis of Streptococcus pneumoniae meningitis. J Clin Microbiol 36: 2346–2348.[Abstract/Free Full Text]
  25. Cao XT, Ngo TN, Kneen R, Bethell D, Le TD, Nguyen TT, Pham TT, Truong DL, Solomon T, Wills B, Parry CM, 2004. Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission. Trop Med Int Health 9: 573–581.[ISI][Medline]
  26. Ward JI, Margolis HS, Lum MK, Fraser DW, Bender TR, Anderson P, 1981. Haemophilus influenzae disease in Alaskan Eskimos: characteristics of a population with an unusual incidence of invasive disease. Lancet 1: 1281–1285.[ISI][Medline]
  27. Hanna JN, Wild BE, 1991. Bacterial meningitis in children under five years of age in Western Australia. Med J Aust 155: 160–164.[ISI][Medline]
  28. Rerks-Ngam S, Treleaven S, Chunsuttiwat S, Muangchana C, Jolley D, Brooks A, Dejiselert S, Varintarwat S, Guiver M, Kunasol P, Maynard JE, Biggs B, Steinhoff M, 2004. Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand. Vaccine 22: 975–983.[ISI][Medline]
  29. Yang Y, Shen X, Jiang Z, Liu X, Leng Z, Lu D, Rao J, Liu J, Chang L, 1998. Study on Haemophilus influenzae type b diseases in China: the past, present and future. Pediatr Infect Dis J 17: S159–S165.[ISI][Medline]
  30. Vutuc C, Kunze M, 1993. Incidence of Haemophilus influenzae meningitis in Austria. Wien Klin Wochenschr 105: 59–60.[ISI][Medline]
  31. Simarro E, Ruiz J, Gomez J, Ortega MG, Vicente C, Martinez L, Perez J, 2000. Haemophilus influenzae infections in children less than 5 years of age in the community of Murcia during the 1992–1999 period. Enferm Infecc Microbiol Clin 18: 325–328.[Medline]
  32. Syrogiannopoulos GA, Mitselos CJ, Beratis NG, 1995. Childhood bacterial meningitis in southwestern Greece: a population-based study. Clin Infect Dis 21: 1471–1473.[ISI][Medline]
  33. Gessner BD, Sutanto A, Linehan M, Djelantik IG, Fletcher T, Gerudug IK, Ingerani , Mercer D, Moniaga V, Moulton LH, Moulton LH, Mulholland K, Nelson C, Soemohardjo S, Steinhoff M, Widjaya A, Stoeckel P, Maynard J, Arjoso S, 2005. Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial. Lancet 365: 43–52.[ISI][Medline]
  34. Prasad K, Singhal T, Jain N, Gupta PK, 2004. Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis. Cochrane Database Syst Rev CD001832.
  35. Marcon MJ, Hamoudi AC, Cannon HJ, 1984. Comparative laboratory evaluation of three antigen detection methods for diagnosis of Haemophilus influenzae type b disease. J Clin Microbiol 19: 333–337.[Abstract/Free Full Text]
  36. Scheifele DW, Daum RS, Syriopoulou VP, Siber GR, Smith AL, 1979. Comparison of two antigen detection techniques in a primate model of Haemophilus influenzae type b infection. Infect Immun 26: 827–831.[Abstract/Free Full Text]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ANH, D. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ANH, D. D.
Related Collections
Right arrow Bacterial Infection
Right arrow Epidemiology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS