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A review of Hib epidemiology in Asia

Lolekha S, Cooksley G, Chan V, Isahak I, Ismael S, John J, et al.

Southeast Asian J. Trop. Med. Public Health, 2000 Dec;31(4):650-7.
PMID: 11414406

Meningitis due to an invasive Haemophilus influenzae type b (Hib) infection, has been previously perceived to be relatively uncommon in Asia. However, the incidence of disease and its impact may have been underestimated. In addition to a lack of microbiological facilities in some hospitals, difficulties in culturing the organism and the widespread use of antibiotics may have hidden the true incidence of the disease in some countries. Furthermore, the reported disease burden probably underestimates the incidence of Hib pneumonia. The epidemiology of invasive Hib disease for various Asian nations is reviewed in this paper. Hospital-based studies show that Hib is a major cause of bacterial meningitis and/or pneumonia in the Philippines, India, Thailand, Malaysia, Indonesia and Vietnam. Singapore and Hong Kong have a low incidence of infection compared with Western and other Asian nations. This low incidence is not due to a higher level of natural protective antibodies, but may be related to an interaction between environmental and genetic factors. Therefore the widespread belief that Hib infection is unimportant in Asia does not refer to Asia as a whole and possibly to Chinese patients only, and failure to recognize this has serious implications. The inclusion of Hib vaccine in the routine infant immunization schedule in many industrialized nations has significantly reduced the incidence of invasive disease. Recent studies have shown Hib vaccination is also effective in preventing invasive disease in children in developing countries. While population-based data may be required to confirm the need for public-funded infant Hib immunization in Asia, its introduction in countries with a high incidence of Hib meningitis and/or pneumonia has the potential to significantly improve pediatric health and survival.

Matched MeSH terms: Haemophilus Infections/microbiology; Haemophilus Infections/epidemiology*; Haemophilus Infections/prevention & control
Fulltext Epidemiology of Haemophilus influenzae invasive disease in hospitalised Kelantanese children, 1985-1994

Nik Khairulddin NY, Choo KE, Johari MR

Singapore Med J, 1999 Feb;40(2):96-100.
PMID: 10414167

Data is lacking with regard to the epidemiology of invasive haemophilus influenzae (HI) disease in Malaysia. This study was carried out to document the epidemiology of invasive HI disease in hospitalised Kelantanese children.

Matched MeSH terms: Haemophilus Infections/epidemiology*
Phylogenetic relationship of non-typeable Haemophilus influenzae isolated in Malaysia

Mohd-Zain Z, Kamsani NH, Ahmad N, Clarke SC

Infect Genet Evol, 2015 Dec;36:240-3.
PMID: 26394107 DOI: 10.1016/j.meegid.2015.09.017

The epidemiology of non-typeable Haemophilus influenzae (NTHi) remains poorly understood. We therefore sought to determine the genetic relationship of 25 NTHi isolated from various states in Malaysia using multilocus sequence typing (MLST). The majority of isolates were obtained from sputum. There were 24 novel sequence types (STs). Eight isolates were single-locus variants, the remainder being singletons. Clustering was not based on clinical site of isolation or geographical origin. Despite the limited number of isolates examined in this study, we demonstrate that NTHi isolates in Malaysia are diverse and warrant further investigation.

Matched MeSH terms: Haemophilus Infections
Type b Haemophilus influenzae endocarditis in children: case report and review of the literature

Malik AS

Ann Trop Paediatr, 1995 Sep;15(3):193-5.
PMID: 8534036

Haemophilus influenzae type b (Hib) endocarditis is a rare but potentially lethal condition. Only ten cases have been reported in the English literature. This report describes an 8-month-old Malay child with a ventricular septal defect who developed Hib endocarditis and died after 4 weeks of hospitalization. The literature is reviewed and previously reported cases summarized.

Matched MeSH terms: Haemophilus Infections/diagnosis*; Haemophilus Infections/drug therapy
Serotyping of Haemophilus paragallinarum isolated in Malaysia

Zain ZB, Iritani Y

J Vet Med Sci, 1992 Apr;54(2):363-5.
PMID: 1606267
Matched MeSH terms: Haemophilus Infections/microbiology; Haemophilus Infections/veterinary*
Fulltext High frequency of Haemophilus influenzae associated with respiratory tract infections among Malaysian Hajj pilgrims

Nik Zuraina NMN, Sarimah A, Suharni M, Hasan H, Suraiya S

J Infect Public Health, 2018 08 07;11(6):878-883.
PMID: 30097415 DOI: 10.1016/j.jiph.2018.07.010

BACKGROUND: Overcrowding during the annual Hajj pilgrimage has been known to increase the risk of infectious diseases transmission. Despite the high prevalence of respiratory illness among Malaysian Hajj pilgrims, knowledge about the etiologic pathogens is yet very limited. Thus, this study aimed to determine the spectrum of bacterial respiratory pathogens among the Hajj pilgrims returning to Malaysia in year 2016.
METHODS: Expectorated sputum specimens were collected from the Hajj pilgrims with symptomatic respiratory tract infections (RTIs). Subsequently, the bacterial pathogens were identified using the standard bacteriological culture method and Vitek II system.
RESULTS: This study indicated that 255 (87.33%) out of 292 cultured sputa were positive with at least one potential pathogenic bacteria. Out of 345 total bacterial isolates, 60% (n=207) were Haemophilus influenzae, which was associated with both single bacterium infection (132/173, 76.3%) and multiple bacterial infections (75/82, 91.5%). The other bacterial isolates included; Klebsiella pneumoniae (n=37, 10.7%), Moraxella catarrhalis (n=27, 7.8%), Haemophilus parainfluenzae (n=25, 7.2%), Streptococcus group G (n=18, 5.2%), Klebsiella spesies (n=16, 4.6%), Streptococcus pneumoniae (n=11, 3.2%) and few other organisms.
CONCLUSION: High frequency of H. influenzae was isolated from Malaysian Hajj pilgrims, especially those with respiratory symptoms. Further study should evaluate the actual pathogenicity of the organism and the interactions between the respiratory microbiota towards developing effective prevention strategies of RTIs among the local pilgrims.

Matched MeSH terms: Haemophilus Infections/microbiology; Haemophilus Infections/epidemiology*
Economic evaluations of Haemophilus influenzae type b (Hib) vaccine: a systematic review

Chongmelaxme B, Hammanee M, Phooaphirak W, Kotirum S, Hutubessy R, Chaiyakunapruk N

J Med Econ, 2017 Oct;20(10):1094-1106.
PMID: 28737468 DOI: 10.1080/13696998.2017.1359181

AIMS: The World Health Organization (WHO) recommends the use of Haemophilus influenzae type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in their national immunization programs. This systematic review aimed to update published economic evaluations of Hib vaccinations and to determine factors that potentially affected their cost-effectiveness.
METHODS: Searches were performed from the inception until December 2015 using 13 databases: CAB direct; CEA registry; EconLit; EMBASE; E-library; NHSEED; PAHO; POPLINE; PubMed; Redalyc project; RePEc; SciELO; and WHOLIS. Reference lists of relevant studies and grey literature were also searched. Full economic evaluations of Hib vaccination with results of costs and outcomes were included. The WHO checklist was used to evaluate the quality of the included studies. Data from eligible studies were extracted using a standardized data collection form.
RESULTS: Out of 830 articles, 27 were included. Almost half of the studies (12/27) were conducted in high-income countries. Twelve studies (12/27) investigated the Hib vaccine as an addition to the existing vaccination program. Most studies (17/27) examined a 3-dose schedule of Hib vaccine. Nineteen studies (19/27) reported the model used, where all were decision tree models. Most of the studies (23/27) demonstrated an economic value of Hib vaccination programs, key influential parameters being incidence rates of Hib disease and vaccine price.
CONCLUSIONS: Hib vaccination programs are mostly found to be cost-effective across geographic regions and country income levels, and Hib vaccination is recommended for inclusion into all national immunization programs. The findings are expected to support policy-makers for making decisions on allocating limited resources of the Hib vaccination program effectively.

Matched MeSH terms: Haemophilus Infections/prevention & control*
Fulltext A microbiological study of genital ulcers in Kuala Lumpur

Zainah S, Cheong YM, Sinniah M, Gan AT, Akbal K

Med J Malaysia, 1991 Sep;46(3):274-82.
PMID: 1839925

The microbial aetiology of genital ulcers was studied in 249 patients (241 men and 8 women) attending a Sexually Transmitted Disease Clinic in Kuala Lumpur, Malaysia. Herpes simplex virus type 2 was isolated in 48 (19.2%) patients, Haemophilus ducreyi from 22 (8.8%), Neisseria gonorrhoeae from seven (2.8%) and Chlamydia trachomatis from four (1.6%). Syphilis was diagnosed in 18 (7.2%) patients on the basis of dark field microscopy. Two (0.8%) patients were found to have both chancroid and syphilis and one (0.5%) had both gonorrhoea and syphilis. No organism was isolated in the remaining 151 (61.5%) patients. Overall, the accuracy of clinical diagnosis was 58% for single infection, 67% for herpes, 63% for syphilis, 47% for chancroid and 0% for lymphogranuloma venereum. Therefore, our study confirms the need for laboratory tests to diagnose accurately the aetiology of genital ulcer disease.

Matched MeSH terms: Haemophilus Infections/microbiology
Fulltext Antibiotic susceptibility profile of Haemophilus influenzae and transfer of co-trimoxazole resistance determinants

Mohd-Zain Z, Kamsani NH, Ismail IS, Ahmad N

Trop Biomed, 2012 Sep;29(3):372-80.
PMID: 23018500 MyJurnal

Prior to the implementation of Haemophilus influenzae type b vaccination worldwide, H. influenzae has been one of the main causative agents of community acquired pneumonia and meningitis in children. Due to the lack of information on the characteristics of the H. influenzae isolates that have previously been collected in Malaysia, the H. influenzae were assessed of their microbial susceptibility to commonly used antibiotics. Emphasis was made on strains that were resistance to co-trimoxazole (SXT) and their mode of transfer of the antibiotic resistance determinants were examined. A collection of 34 H. influenzae isolates was serotyped and antimicrobial susceptibility tests were performed to 11 antibiotics. To the isolates that were found to be resistant to co-trimoxazole, minimum inhibition concentration (MIC) to SXT was performed using Etest while agar dilution method was used to measure the individual MICs of trimethoprim (TMP) and sulfamethoxazole (SUL). These isolates were also examined for presence of plasmid by PCR and isolation method. Conjugal transfers of SXT-resistant genes to SXT-susceptible hosts were performed to determine their rate of transfer. Result showed that 20.6% of the total number of isolates was serotype B while the remaining was non-typeable. Antimicrobial susceptibility profile of all the isolates revealed that 58.8% was resistant to at least one antibiotic. Majority of these isolates were equally resistant to ampicillin and tetracycline (29.4% each), followed by resistance to SXT (26.5%). From nine isolates that were found to be SXT-resistant, five contained plasmid/s. Conjugal transfer experiment showed that these five isolates with plasmid transferred SXT-resistance determinants at a higher frequency than those without. From these observations, it is postulated that plasmid is not involved in the transfer of SXT-resistance genes but presence of plasmid facilitates their transfer. The information obtained from this study provides some basic knowledge on the antimicrobial susceptibility pattern of the H. influenzae isolates and their mode of transfer of SXT-resistance genes.

Matched MeSH terms: Haemophilus Infections/drug therapy; Haemophilus Infections/microbiology*
Fulltext Molecular insights of co-trimoxazole resistance genes in Haemophilus influenzae isolated in Malaysia

Mohd-Zain Z, Kamsani NH, Ahmad N

Trop Biomed, 2013 Dec;30(4):584-90.
PMID: 24522126 MyJurnal

In the last few decades, co-trimoxazole (SXT), an antibacterial combination of trimethoprim and sulfamethoxazole, has been used for treatment of upper respiratory tract infection due to Haemophilus influenzae. The usage of this antibiotic has become less important due to emergence of SXT-resistant strains worldwide. Most reports associate SXT resistance to the presence of variants of dihydrofolate reductase (DHFR) dfrA genes which are responsible for trimethoprim resistance; while the sulfamethoxazole (SMX) resistance are due to sulfonamide (SUL) genes sul1 and sul2 and/or mutation in the chromosomal (folP) gene encoding dihydropteroate synthetase (DHPS). This study aims to detect and analyse the genes that are involved in SXT resistance in H. influenzae strains that were isolated in Malaysia. Primers targeting for variants of dfrA, fol and sul genes were used to amplify the genes in nine SXT-resistant strains. The products of amplification were sequenced and multiple alignments of the assembled sequences of the local strains were compared to the sequences of other H. influenzae strains in the Genbank. Of the five variants of the dhfA genes, dfrA1 was detected in three out of the nine strains. In contrast to intermediate strains, at least one variant of folP genes was detected in the resistant strains. Multiple nucleotide alignment of this gene revealed that strain H152 was genetically different from the others due to a 15-bp nucleotide insert in folP gene. The sequence of the insert was similar to the insert in folP of H. influenzae strain A12, a strain isolated in United Kingdom. None of the strains had sul1 gene but sul2 gene was detected in four strains. Preliminary study on the limited number of samples shows that the TMP resistance was attributed to mainly to dfrA1 and the SMX was due to folP genes. Presence of sul2 in addition to folP in seven strains apparently had increased their level of resistance. A strain that lacked sul1 or sul2 gene, its resistance to sulfonamide was attributed to a 15-bp DNA insert in the folP gene.

Matched MeSH terms: Haemophilus Infections/microbiology*
Fulltext Economic Evaluation and Budget Impact Analysis of Vaccination against Haemophilus influenzae Type b Infection in Thailand

Kotirum S, Muangchana C, Techathawat S, Dilokthornsakul P, Wu DB, Chaiyakunapruk N

Front Public Health, 2017;5:289.
PMID: 29209602 DOI: 10.3389/fpubh.2017.00289

Current study aimed to estimate clinical and economic outcomes of providing the Haemophilus influenzae type b (Hib) vaccination as a national vaccine immunization program in Thailand. A decision tree combined with Markov model was developed to simulate relevant costs and health outcomes covering lifetime horizon in societal and health care payer perspectives. This analysis considered children aged under 5 years old whom preventive vaccine of Hib infection are indicated. Two combined Hib vaccination schedules were considered: three-dose series (3 + 0) and three-dose series plus a booster does (3 + 1) compared with no vaccination. Budget impact analysis was also performed under Thai government perspective. The outcomes were reported as Hib-infected cases averted and incremental cost-effectiveness ratios (ICERs) in 2014 Thai baht (THB) ($) per quality-adjusted life year (QALY) gained. In base-case scenario, the model estimates that 3,960 infected cases, 59 disability cases, and 97 deaths can be prevented by national Hib vaccination program. The ICER for 3 + 0 schedule was THB 1,099 ($34) per QALY gained under societal perspective. The model was sensitive to pneumonia incidence among aged under 5 years old and direct non-medical care cost per episode of Hib pneumonia. Hib vaccination is very cost-effective in the Thai context. The budget impact analysis showed that Thai government needed to invest an additional budget of 110 ($3.4) million to implement Hib vaccination program. Policy makers should consider our findings for adopting this vaccine into national immunization program.

Matched MeSH terms: Haemophilus Infections