Hib Pneumonia Research Articles

Impact of Haemophilus influenza immunization on hospitalized acute respiratory infections

Abstract Background Immunization is the most cost-effective measure to combat communicable diseases in childhood. Haemophilus influenza (Hib) vaccine was included in the Tunisian expanded program of immunization for the first time in 2002 (Hib Vaccine monovalent) and is currently combined with the pneumococcal vaccine(Hib vaccine pentavalent combination) since April 2019. We aimed to assess impact of Hib vaccine on Respiratory Infection(RI) admissions in children aged up to 3 years. Methods It was a cohort study from January 1, 2002 to December 31, 2013. All Respiratory Infection (RI) admissions in children aged up to 3 years in the university hospital of Monastir(Tunisia) were enrolled. Results Admissions for RI represented 17.6% (CI95%: 17.3-18.1) of all communicable diseases hospitalizations (n = 6 061/34 289). The median age was 22 years (IQR: 3-52). Admission for Pneumonia with Streptococcus Pneumoniae (SP) increased significantly during study period (b = 25.9 (p < 0.0001)) especially in children up to 5 years old (b = 10.6) and in elderly (b = 6.0). Among children up to 3 years old, the Crude incidence rate per 100,000 for Hib pneumonia admission were 11.6 in Non-Vaccinated Cohort (NVC), 10.6 in Vaccinated Cohort (VC) by protocol 1 (Hib Vaccine monovalent) and 0.80 in VC by protocol 2 (Hib vaccine pentavalent combination).The relative risk reduction was 99% for protocol 2 (p < 0.001). Conclusions Admissions for RI in a tertiary level hospital were common with an increasing trend. The Hib immunization program, in particular the second protocol (pentavalent combination), has had a positive impact on the reduction of related acute diseases. Key messages The Hib immunization program, has had a positive impact on the reduction of related acute diseases. The “Hib vaccine pentavalent combination “is more efficient than “Hib Vaccine monovalent”.

Epidemiology of Respiratory Pathogens Among Children Hospitalized for Pneumonia in Xiamen: A Retrospective Study.

ObjectivesTo investigate the etiology of common respiratory pathogens in children < 2 years of age hospitalized with pneumonia in Xiamen from 2014 to 2017.MethodsThe medical records of 5581 children with pneumonia were retrospectively reviewed. Direct immunofluorescent test was used for respiratory virus testing. Bacteria were detected by conventional culture method. The results of pathogen detection at admission were analyzed as well as the clinical outcomes of children.ResultsThe burden of hospitalized children with pneumonia was highest among infants < 6 months old (58.2%). Respiratory syncytial virus (RSV) was the most common respiratory virus (26.0%) followed by parainfluenza (4.8%) and adenovirus (3.2%). Haemophilus influenzae was the most common bacteria detected (16.6%) followed by Moraxella catarrhalis (13.4%), Staphylococcus aureus (13.0%), Streptococcus pneumoniae (12.3%), Escherichia coli (5.1%) and Klebsiella pneumoniae (4.8%). Notably, RSV and K. pneumoniae were detected more frequently in severe pneumonia (35.0% and 10.9%) versus mild pneumonia (25.6% and 4.6%), with higher rates of ICU admissions, longer hospital stays and higher hospital costs compared to those infected with other respiratory pathogens.ConclusionsAmong children < 2 years of age hospitalized with pneumonia in Xiamen, RSV was the most common respiratory virus, while H. influenzae and S. pneumoniae remained the predominant bacterial pathogens detected. Considering the low implementation rate of vaccines against pneumococcal and Hib pneumonia in China, there is an urgent need to increase both vaccination rates to reduce pneumococcal and Hib disease burden.

Trends and health burden of hospitalized acute respiratory infections and impact of Haemophilus influenza immunization in a Tunisian university hospital: a twelve-year study

ABSTRACT Background We aimed to describe the episodes and trends of admissions for community-acquired Respiratory Infections (RI) over a 12-year period and to assess the impact of Haemophilus influenza type b (Hib) vaccine on RI admissions in children aged up to 3 years. Methods We conducted a twelve-year retrospective observational study on all community-acquired RI admitted to Fattouma Bourguiba Hospital in Monastir Governorate (Tunisia) from 1 January 2002 to 31 December 2013. RI cases were selected from the Regional Registry of Hospital Morbidity. Data were coded according to ICD-10. To assess the impact of the Hib vaccine, three cohorts were defined based on vaccine status (unvaccinated cohort, first vaccinated cohort (VC) by monovalent form and second VC by pentavalent combination). Results Admissions for RI represented 17.6% (CI95%: 17.3–18.1) of all communicable diseases hospitalizations (n = 6 061/34 289). The crude incidence rates (CIR) per 100,000 inh were 24.2 for upper RI (URI) and 77.5 and for Lower RI (LRI) (p < 0.0001). Pneumonias represented 53.9% of LRI. Sex-ratio (male/female) was 1.12 for URI and 1.64 for LRI (p < 0.0001). At admission, the median age was 22 years (IQR: 3–52). Admission for Pneumonia increased significantly during study period (slope ‘b’ = 5.16; p < 0.0001) especially in children up to 5 years old (slope ‘b’ = 5.53) and in elderly (slope ‘b’ = 2.13). Among children up to 3 years old, the CIRs per 100,000 for Hib pneumonia admission were 11.6 in Non-Vaccinated Cohort (NVC), 10.6 in Vaccinated Cohort (VC) by protocol 1 (Hib Vaccine monovalent) and 0.80 in VC by protocol 2 (pentavalent vaccine combination).The relative risk reduction was 99% for protocol 2 (p < 0.001). Conclusion Admissions for RI in a tertiary level hospital were common with an increasing trend. The Hib immunization program, in particular the pentavalent combination, has had a positive impact on the reduction of related acute diseases.

Realizing the need of inclusion of rotavirus vaccine in expanded program on immunization in Sindh, Pakistan

The basic goal of the expanded program on immunization (EPI) is to assure the proper immunization services that aids in preserving and promoting the health of children. The foundation of EPI in Pakistan was prompted and initiated by the World Health Organization (WHO) in 19781. The current EPI of Pakistan has vaccines for Tuberculosis, Poliomyelitis, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus Influenza-b (Hib) Pneumonia, Meningitis, and Measles. However, it doesn't include the most important Rotavirus vaccine which is internationally included in EPI of other 90 countries. Despite the advent of Rotavirus vaccine a decade ago, it is the most common cause of severe childhood diarrhea. Globally it results in more than half a million deaths among children of less than 5 years of age per annum. In 2006 first rotavirus vaccine was introduced in Finland (US) in 2 forms, Rotarix and Rotteq. Both had the maximum potential effect if given before 8 months of age. In the United States, studies depicted that after the introduction of the vaccine in 2006 mortality has reduced by more than two thirds. According to WHO, diarrhea has the 3rd highest rates of mortality in children amongst all infectious diseases.

Cost-effectiveness of the Haemophilus influenzae type b vaccine for infants in mainland China

ABSTRACTObjective: The aims of this study were to estimate the cost-effectiveness of the Haemophilus influenzae type b (Hib) vaccine for the prevention of childhood pneumonia, meningitis and other vaccine-preventable diseases in mainland China from a societal perspective and to provide information about the addition of the Hib vaccine to Chinese immunization programs.Methods: A decision tree and the Markov model were used to estimate the costs and effectiveness of the Hib vaccine versus no Hib vaccine for a birth cohort of 100,000 children in 2016. The disease burden was estimated from the literature, statistical yearbooks and field surveys. Vaccine costs were calculated from government reports and the United Nations International Children's Emergency Fund (UNICEF) website. The WHO cost-effectiveness thresholds were used to evaluate the Hib vaccine intervention. A one-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the parameter uncertainties.Results: Within the hypothetical cohort, under a vaccination coverage of 90%, the Hib vaccine could reduce 91.4% of Hib pneumonia and 88.3% of Hib meningitis; the Hib vaccine could also prevent 25 deaths, 24 meningitis sequelae cases and 9 hearing loss cases caused by Hib infection. From a societal perspective, the incremental cost-effectiveness ratio (ICER) of the Hib vaccine compared with no vaccination was US$ 13,640.1 at the market price, which was less than 3 times the GDP per capita of China in 2016. The ICER of the Hib vaccine was US$ −59,122.9 at the UNICEF price, indicating a cost savings. The largest portion of the uncertainty in the result was caused by the annual incidence of all-cause pneumonia, proportion of pneumonia caused by Hi, vaccine costs per dose, annual incidence of Hib meningitis and costs per episode of meningitis. The models were robust considering parameter uncertainties.Conclusion: The Hib vaccine is a cost-effective intervention among children in mainland China. The cost of Hib vaccine should be reduced, and it should be introduced into Chinese immunization programs.

Economic Evaluation and Budget Impact Analysis of Vaccination against Haemophilus influenzae Type b Infection in Thailand

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.

Malnutrition amongst Under-Five Years Children in Swat, Pakistan: Prevalence and Risk Factors

Purpose: To identify malnourished cases and determine their relationship with weaning time and socioeconomic factors in under-5 children in Swat, Pakistan.Methods: This cross-sectional study was conducted at the Pediatric Ward and Outpatients Department (OPD), Saidu Teaching Hospital, Swat, Pakistan using case files from October to December 2011.Results: A total of 186 children were studied to identify malnutrition, out of which 101 (37.7 %) were male and 85 (32.0 %) female. Moreover, 95 (35.7 %) of the mothers were &lt; 30 years of age and 91 (34.0 %) &gt; 30 years. About 33.7 % of the children were weaned before the age of 4 months. The maternal age of 28.6 % of the malnourished children was &lt; 20 years, and about 2l % of the malnourished children were not immunized against eight EPI (Expanded Program on Immunization) target diseases, viz, poliomyelitis, neonatal tetanus, measles, diphtheria, pertussis (whooping cough), hepatitis-B, Hib pneumonia &amp; meningitis, and childhood tuberculosis. Respondents from urban location 98 (36.7 %), while 88 (33.0 %). Based on Gomezfs classification, out of 186 children, 19 (7.1 %) werevictims of malnutrition; mothers of 35.6 % of the children were uneducated and 25.5 % had primary level (5 years) education. The number of siblings per mother was . 5 in the case of 64.8 % of the malnourished children. More than half of the children were at risk of malnutrition.Conclusion: The incidence of malnutrition is about the same for both male and female children. Risk factors for malnutrition in the children include lack of education, teenage pregnancy, lack of immunization, and large family size.Keywords: Malnutrition, Gomezfs classification, Weaning time, Risk factors, Teenage pregnancy, Swat

Pentavalent Vaccine and Adverse Events Following Immunization—Untangling the Misinterpretations

In April 2008, the National Technical Group on Immunization (NTAGI) Sub-committee on H. influenza type b (Hib) vaccine recommended that Hib containing pentavalent vaccine should be introduced in the country. Subsequently liquid pentavalent vaccine (LPV) was launched in the Kerala and Tamil Nadu on a pilot basis in December 2011. The introduction of LPV in these two states was followed by reported deaths in infants who had received LPV. An exhaustive summary of media reports and previous literature has since been made available at various fora which have been supplemented with estimations of the damage the LPV may cause. It has thus been concluded that the LPV is bound to cause more number of infant deaths than it will save from Hib meningitis and pneumonia. The current paper aims to clear some of the misinterpretations and miscalculations so that lives of 72,000 infants can be saved.

Estimation of the herd protection of Haemophilus influenzae type b conjugate vaccine against radiologically confirmed pneumonia in children under 2 years old in Dhaka, Bangladesh

Background Herd protection of Haemophilus influenzae type b (Hib) conjugate vaccine has been associated with excessive decrease of invasive Hib diseases, i.e., pneumonia and meningitis, with increased national or regional Hib vaccine coverage. Only a few studies have examined herd protection at the individual level and even less evidence is available from Asia. We examined Hib vaccine herd protection against radiologically confirmed pneumonia among children less than 2 years old.Methods We incorporated data from a matched case-control study and a vaccine coverage survey in Dhaka, Bangladesh. Pneumonia cases (n=343) were confirmed by radiology. For each case, two controls with conditions other than pneumonia or meningitis were selected from the same hospital. Hib vaccine coverage was calculated as percentages of children who received at least 2 doses of Hib vaccine from a survey in the neighborhood centered on each case and control. Conditional logistic regression was fit to examine the association between vaccine coverage and risk of radiologically confirmed pneumonia.Results Neighborhood Hib vaccine coverage varied from 0% to 63.5% for cases and from 8.7% to 61.5% for controls, respectively. Cases were less likely to have neighborhood coverage higher than 20% (OR=0.49, 0.52, 0.55, and 0.69 for coverage 20–29%, 30–39%, 40–49%, and ≥50%, respectively) than coverage <20%, compared to controls, although the estimates for coverage 40–49% and ≥50% were not statistically significant.Conclusions The study indicates that Hib vaccine may provide herd protection, even when the coverage is as low as 20–39%, in a low-income country. Asian countries should consider herd protection in implementing effective vaccine policy with limited resources.

Cost-effectiveness of Haemophilus influenzae type b (Hib) vaccine introduction in the universal immunization schedule in Haryana State, India

In India, Haemophilus influenzae type b (Hib) vaccine introduction in the universal immunization programme requires evidence of its potential health impact and cost-effectiveness, as it is a costly vaccine. Since childhood mortality, vaccination coverage and health service utilization vary across states, the cost-effectiveness of introducing Hib vaccine was studied in Haryana state. A mathematical model was used to compare scenarios with and without Hib vaccination to estimate the cost-effectiveness of Hib vaccine in Haryana from 2010 to 2024. Demographic and National Family Health Surveys were used to estimate vaccination coverage and mortality rates among children under 5. Hib pneumonia, Hib meningitis and invasive Hib disease incidence were based on Indian studies. Vaccine and syringe prices of the UNICEF supply division were used. Cost-effectiveness from government and societal perspectives was calculated as the net incremental cost per unit of health benefit gained [disability-adjusted life years (DALYs) averted, life years saved, Hib cases averted, Hib deaths averted]. Sensitivity analysis was done using variation in parameter estimates among different states of India. The incremental cost of Hib vaccine introduction from a government and a societal perspective was estimated to be US$81.4 and US$27.5 million, respectively, from 2010 to 2024. Vaccination of 73.3, 71.6 and 67.4 million children with first, second and third dose of pentavalent vaccine, respectively, would avert 7 067 817 cases, 31 331 deaths and 994 564 DALYs. Incremental cost per DALY averted from a government (US$819) and a societal perspective (US$277) was found to be less than the per capita gross national income of India in 2009. In sensitivity analysis, Hib vaccine introduction remained cost-effective for India. Hib vaccine introduction is a cost-effective strategy in India.

Haemophilusinfluenzae type b pneumonia in Egyptian children under five years: A step toward the identification of the real burden in our community by the use of real-time polymerase chain reaction

Haemophilus influenzae (Hi) causes more than 3 million cases of serious disease, mainly meningitis and pneumonia in children less than 5years old with approximately 386,000 deaths each year worldwide. The presence or absence of a polysaccharide capsule is an important distinguishing characteristic of H. influenzae species. The polysaccharide capsule can be serologically classified into six serotypes (a to f). Invasive Hi diseases in children were almost exclusively caused by serotype b (Hib). To the best of our knowledge, the real burden of Hib pneumonia in Egypt is not clarified. Yet, few studies are published and concerned with Hib sepsis among neonates or Hib meningitis in children. We aimed in this study to identify the frequency of Hib pneumonia among Egyptian children below five years by the use of real-time polymerase chain reaction (PCR) technique, with insight on antimicrobial resistance of Hib strains in the Egyptian community. One hundred patients with community-acquired pneumonia were investigated for Hib by both real-time PCR and bacterial culture. Haemophilus influenzae type b was diagnosed in 31% of the examined population by PCR, with sensitivity of 100% (95% CI: 0.86–1), specificity 100% (65% CI: 0.93–1), positive predictive value (PPV) 100% (95% CI: 0.83–1), and negative predictive value (NPV) 100% (95% CI: 0.93–1). Blood culture was positive in 12 patients only, with a sensitivity of 38% (95% CI: 0.22–0.57), a specificity of 100% (65% CI: 0.93–1), PPV 100% (95% CI: 0.69–1), and NPV 77% (95% CI: 0.68–0.86). Isolated Hib strains were sensitive to ceftriaxon in 91% of cases, followed by ampicillins in 31% and cotrimoxazole in 17%. Three patients had multidrug resistant strains of Hib. ConclusionHaemophilus influenzae type b infection is still an important and frequent pathogen causing community-acquired pneumonia in Egypt with changeable antibiotic sensitivity pattern. PCR represented a sensitive and rapid tool for the diagnosis of Hib pneumonia. Governmental plans to eradicate Hib in our community with the introduction of Hib conjugate vaccine in the national immunization program became indispensable.

Rapid assessment of Hib disease burden in Vietnam

BackgroundSeveral countries have applied the Haemophilus influenzae type b (Hib) rapid assessment tool (RAT) to estimate the burden of Hib disease where resources for hospital- or population-based surveillance are limited. In Vietnam, we used the Hib RAT to estimate the burden of Hib pneumonia and meningitis prior to Hib vaccine introduction.MethodsLaboratory, hospitalization and mortality data were collected for the period January 2004 through December 2005 from five representative hospitals. Based on the WHO Hib RAT protocol, standardized MS Excel spreadsheets were completed to generate meningitis and pneumonia case and death figures.ResultsWe found 35 to 77 Hib meningitis deaths and 441 to 957 Hib pneumonia deaths among children < 5 years of age annually in Vietnam. Overall, the incidence of Hib meningitis was estimated at 18/100,000 (95% confidence interval, CI, 15.1-21.6). The estimated Hib meningitis incidence in children < 5 years age was higher in Ho Chi Minh City (22.5/100,000 [95% CI, 18.4-27.5]) compared to Hanoi (9.8/100,000 [95% CI, 6.5-14.8]). The Hib RAT suggests that there are a total of 883 to 1,915 cases of Hib meningitis and 4,414 to 9,574 cases of Hib pneumonia per year in Vietnam.ConclusionsIn Hanoi, the estimated incidence of Hib meningitis for children < 5 years of age was similar to that described in previous population-based studies of Hib meningitis conducted from 1999 through 2002. Results from the Hib RAT suggest that there is a substantial, yet unmeasured, disease burden associated with Hib pneumonia in Vietnamese children.

1317 Rapid Diagnosis of Haemophilus Influenza Type B Pneumonia by Polymerase Chain Reaction in Unvaccinated Egyptian Children Under Five Years

Background: Haemophilus influenza type B (Hib)is an important cause of meningitis, Community-acquired pneumonia (CAP), andsepticemia. Hib disease results in significantmorbidity and mortality among children. The burdenof Hib pneumonia in Egypt is unclear thus thereare no scheduled programs for Hib surveillance, case definition, diagnostic modalities or evenvaccination.Aim: To highlight the magnitude of Hib pneumoniaamong Egyptian children, and to assess theirpattern of antibiotic sensitivity.Methods: The sera of 100 patients of Egyptianunvaccinated children below five years, presentedwith community- acquired pneumonia wereinvestigated for Hib pneumonia by Polymerasechain reaction (by ELIZA) and blood cultures.Antibiotic sensitivity was done for Hib isolates bythe use of disc -diffusion method.Results: Hib pneumonia was diagnosed in 31/100of patients by PCR patients, 12 of them were culturepositive.The highest resistance of Hib isolates was tocotrimoxazole (75%) and ampicillin (66.7%). The highest sensitivity was to ceftriaxon (91.7%).PCR had sensitivity of 100%, specificity 74.4 %, Positive Predictive value 39%, Negative PredictiveValue 100% and diagnostic accuracy 81% comparedto blood culture.Conclusion: The frequency of Hib pneumoniaamong unvaccinated children in Egypt is alarming.Combination of PCR and blood culture is necessaryto achieve early diagnosis and appropriate antibioticselection for early diagnosis and better managementof Hib pneumonia.

Childhood Hib vaccination and pneumonia and influenza burden in US seniors

This analysis examines the potential for the elderly to receive indirect protection from pneumonia and influenza (P&I) from vaccination of children. Using data from the Centers for Medicare and Medicaid Services, the National Immunization Survey, and the Behavioral Risk Factor Surveillance System, mixed-effects models were used to assess associations between vaccination coverage and P&I on the state level overall and by urbanicity and income. As vaccination coverage in children increased, the state-level P&I rates in seniors decreased ( β = −0.040, −0.074 to 0.006), where β represents the expected change in the logged age-associated rate of disease increase for a one-percentage point increase in vaccination coverage. Increasing vaccination coverage in the elderly was associated with an increase in P&I rates ( β = 0.045, 0.011–0.077) in seniors. The degree of association was more prominent in urban and high income areas. The consistent associations between influenza in the elderly and vaccination coverage in children suggest that routine vaccination of children may impart some indirect protection to the elderly.

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.

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

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. 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. 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. 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.

Authors' Reply to "Is Hib Vaccine of Economic Value in South Korea?"

We appreciate Dr. Griffiths and colleagues' letter and their interest in our paper (1). They raised quite an important fundamental issue regarding the cost-benefit analysis (CBA) study. In CBA study, many assumptions are needed because of the lack of baseline data, which are the main weakness of this kind of study. We also did several assumptions, which are not verified in other studies. Dr. Griffiths et al. pointed out this. Therefore, the CBA study can be a reference in decision on health policy, especially when the policy on national immunization, but many other discussions are also very important. First, Dr. Griffiths et al. mentioned the unreasonably high price of the Hib vaccine in Korea in our study. It was one of most serious difficulties when gathering information regarding the vaccine price in the conduction of CBA. Thus far, the Hib vaccine has not been included in the Korean universal vaccination, and no data existed regarding the Hib vaccine. Therefore, we went through the vaccine prices in private clinics in 2003. The price of the Hib immunization is KRW 40,000, which includes the vaccine (around KRW27,000-30,000) and administration (around KRW10,000). Based on this data, it was assumed that there would be a 50% reduction in the administrative costs and a 20% reduction in the cost of the Hib vaccine. Therefore, we used KRW26,000 per shot. If the Hib immunization, however, was adopted in a national immunization schedule, the cost of the vaccine would probably be lower due to the economy of scale. Under another scenario, applying US$9 or US$11 per dose as in US, the benefit-cost ratio of Hib immunization in our paper (1) would be increased to 1.52-1.86, and then we could expect the economic efficiency to increase significantly. Second, Dr. Griffiths et al. pointed out the incidence data of Hib infection in this study. The study by Kim et al. (2), which was used to estimate the annual incidence in our study, was the first population-based study and the only report of annual incidence of Hib meningitis in Korea. However, this study did not include Hib infection apart from Hib meningitis. Unavoidably, we had to assume the incidence rate of Hib pneumonia based on United States' epidemiology data (3). To estimate Hib pneumonia in Korea, the proportion of meningitis and pneumonia in US was initially estimated, and the rate was then applied to estimate Korean Hib pneumonia incidence. In addition, the trend of Korean Hib meningitis is not equal to those of other Asian countries; therefore, it is also difficult to assume that Hib pneumonia is more prevalent than Hib meningitis, as in Indonesia. Although a sensitivity analysis was conducted to test uncertainty concerning the incidence of Hib infection, we also recognize that a problem of estimation of the incidence based on other country's epidemiologic data exists. We completely agree with Dr. Griffiths et al. last point. Economic evaluation is just one method available to provide information to help develop policy. Despite the low economic efficiency, we would like to point out that there are a significant number of cases of disease, deaths and sequelae that can be prevented by Hib vaccination. The scope of this study, however, was to test the efficiency of Hib universal immunization based on a CBA. Except for the CBA, other discussions regarding whether Hib vaccination should be included in the Korean national vaccination program are beyond the scope of this study; therefore, discussion on that point was not included.

Is Hib Vaccine of Economic Value in South Korea?

We welcome the article from Shin and colleagues on the cost-benefit of Haemophilus influenzae type b (Hib) immunization in Korea (1). The introduction of Hib vaccine into national immunization programmes has increased considerably during the past few years. While 91 countries had introduced the vaccine in 2005, 138 had done so in 2008 (2). Thirty-three of these additional 46 countries receive support from the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization) for Hib vaccine, while 13 countries have introduced the vaccine with government funds (3). In Asia, the large countries of India, Pakistan and Bangladesh are currently introducing the vaccine. The overall conclusion made by Shin et al. (1) is that Hib vaccine is not economically efficient enough to introduce in Korea, partly due to the relatively high price of Hib vaccine and also due to the low Hib disease incidence. We wish to question this conclusion and some of the assumptions made to derive it. Firstly, Shin et al. used a public sector Hib vaccine price of US$20 per dose which seems unrealistically high. There are no published records of governments paying such a high public sector price for Hib vaccine. The US public sector price is between US$9 and US$11 per dose (4). In Australia, the government pays US$8 per dose (5). Shin et al. (1) states that if the price was less than US$16 per dose the vaccine would be economically efficient. Hence, if the analysis in the paper had been based on a public sector price comparable to other countries, the overall conclusion would have been opposite to their conclusion. The vaccine is in fact cost-saving. Secondly, the assumption made about Hib pneumonia incidence is unclear. The authors cite a reference from the United States for the ratio of pneumonia to meningitis incidence (6), which included only the incidence for invasive Hib disease and not all Hib pneumonias, and indicated that the number of meningitis cases is far higher than the number of pneumonia cases. However, the calculations used to estimate the pneumonia burden of disease were not stated clearly, and there are problems in extrapolating data from countries with such different demographics. In fact, Hib pneumonia is commonly thought to be much more prevalent than Hib meningitis in Asia (7). Lastly, we disagree with the underlying notion of Shin et al. that economic efficiency is only achieved if an intervention is proven to be cost-saving. Governments and policy makers are normally prepared to pay for improvement in the health of their populations. Economic analysis should, therefore, be used as one of many factors to guide the decision to choose among alternative health technologies.

Economic evaluation of delivering Haemophilus influenzae type b vaccine in routine immunization services in Kenya.

Haemophilus influenzae type b (Hib) vaccine was introduced into routine immunization services in Kenya in 2001. We aimed to estimate the cost-effectiveness of Hib vaccine delivery. A model was developed to follow the Kenyan 2004 birth cohort until death, with and without Hib vaccine. Incidence of invasive Hib disease was estimated at Kilifi District Hospital and in the surrounding demographic surveillance system in coastal Kenya. National Hib disease incidence was estimated by adjusting incidence observed by passive hospital surveillance using assumptions about access to care. Case fatality rates were also assumed dependent on access to care. A price of US$ 3.65 per dose of pentavalent diphtheria-tetanus-pertussis-hep B-Hib vaccine was used. Multivariate Monte Carlo simulations were performed in order to assess the impact on the cost-effectiveness ratios of uncertainty in parameter values. The introduction of Hib vaccine reduced the estimated incidence of Hib meningitis per 100,000 children aged < 5 years from 71 to 8; of Hib non-meningitic invasive disease from 61 to 7; and of non-bacteraemic Hib pneumonia from 296 to 34. The costs per discounted disability adjusted life year (DALY) and per discounted death averted were US$ 38 (95% confidence interval, CI: 26-63) and US$ 1197 (95% CI: 814-2021) respectively. Most of the uncertainty in the results was due to uncertain access to care parameters. The break-even pentavalent vaccine price--where incremental Hib vaccination costs equal treatment costs averted from Hib disease--was US$ 1.82 per dose. Hib vaccine is a highly cost-effective intervention in Kenya. It would be cost-saving if the vaccine price was below half of its present level.

Detection of antigenuria for diagnosis of invasiveHaemophilus influenzaetype b disease

Haemophilus influenzae type b (Hib) diseases are responsible for an estimated 400,000 childhood deaths, mostly in developing countries. To determine the value of the Wellcogen quantitative latex agglutination test (LA) in urine for the diagnosis of Hib pneumonia and meningitis. Healthy and sick children aged <5 y were enrolled in Dhaka Shishu (Children's) Hospital. Boiled and non-concentrated urine specimens underwent LA testing. In vaccinated subjects, urine was tested by LA at 24 h, 4-6 and 7-10 d after vaccination. Of 1302 enrolled cases, 201 were healthy (90 Hib vaccine recipients and 111 provided NP) and 1101 were sick with either pneumonia (n=974) or meningitis (n=127). Among the healthy children enrolled, 41 (41/111, 37%) were colonised with Hib and two (2/41, 5%) were positive by LA test. Hib antigenuria among the children who had received Hib vaccination was mainly detected only on day 1 (7/90, 8%) of vaccination. Among the sick children, LA test for Hib antigen was positive for all confirmed cases of Hib pneumonia (10) and meningitis (35). In contrast, none of the urine specimens from the cases with a known aetiology other than Hib (n=104) was positive. Quantitative analysis of antigenuria of sick children showed that it is positive at least up to 1:8 and 1:16 dilutions for pneumonia and meningitis, respectively, in contrast with <or=1:4 for healthy children. In addition to the ten cases of culture-proven Hib, the test detected an additional 16 Hib pneumonia cases among children diagnosed as pneumonia, based on the presence of antigenuria >or=1:8 dilutions. The Wellcogen LA test for Hib using boiled and non-concentrated urine is more sensitive than blood culture alone and is highly specific.