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

OBJECTIVE: 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.

Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in low- and middle-income countries: regional analysis and assessment of major determinants.

OBJECTIVES: To estimate the cost-effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccine in low- and middle-income countries and identify the model variables, which are most important for the result. STUDY DESIGN: A static decision tree model was developed to predict incremental costs and health impacts. Estimates were generated for 4 country groups: countries eligible for funding by the GAVI Alliance in Africa and Asia, lower middle-income countries, and upper middle-income countries. Values, including disease incidence, case fatality rates, and treatment costs, were based on international country estimates and the scientific literature. RESULTS: From the societal perspective, it is estimated that the probability of Hib conjugate vaccine cost saving is 34%-53% in Global Alliance for Vaccines and Immunization eligible African and Asian countries, respectively. In middle-income countries, costs per discounted disability adjusted life year averted are between US$37 and US$733. Variation in vaccine prices and risks of meningitis sequelae and mortality explain most of the difference in results. For all country groups, disease incidence cause the largest part of the uncertainty in the result. CONCLUSIONS: Hib conjugate vaccine is cost saving or highly cost-effective in low- and middle-income settings. This conclusion is especially influenced by the recent decline in Hib conjugate vaccine prices and new data revealing the high costs of lost productivity associated with meningitis sequelae.

Impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccination in India.

OBJECTIVE: To estimate the potential health impact and cost-effectiveness of nationwide Haemophilus influenzae type b (Hib) vaccination in India. STUDY DESIGN: A decision support model was used, bringing together estimates of demography, epidemiology, Hib vaccine effectiveness, Hib vaccine costs, and health care costs. Scenarios favorable and unfavorable to the vaccine were evaluated. State-level analyses indicate where the vaccine might have the greatest impact and value. RESULTS: Between 2012 and 2031, Hib conjugate vaccination is estimated to prevent over 200 000 child deaths (∼1% of deaths in children <5 years of age) in India at an incremental cost of US$127 million per year. From a government perspective, state-level cost-effectiveness ranged from US$192 to US$1033 per discounted disability adjusted life years averted. With the inclusion of household health care costs, cost-effectiveness ranged from US$155-US$939 per discounted disability adjusted life year averted. These values are below the World Health Organization thresholds for cost effectiveness of public health interventions. CONCLUSIONS: Hib conjugate vaccination is a cost-effective intervention in all States of India. This conclusion does not alter with plausible changes in key parameters. Although investment in Hib conjugate vaccination would significantly increase the cost of the Universal Immunization Program, about 15% of the incremental cost would be offset by health care cost savings. Efforts should be made to expedite the nationwide introduction of Hib conjugate vaccination in India.

Comparative economic evaluation of Haemophilus influenzae type b vaccination in Belarus and Uzbekistan.

BACKGROUND: Hib vaccine has gradually been introduced into more and more countries during the past two decades, partly due to GAVI Alliance support to low-income countries. However, since Hib disease burden is difficult to establish in settings with limited diagnostic capacities and since the vaccine continues to be relatively expensive, some Governments remain doubtful about its value leading to concerns about financial sustainability. Similarly, several middle-income countries have not introduced the vaccine. The aim of this study is to estimate and compare the cost-effectiveness of Hib vaccination in a country relying on self-financing (Belarus) and a country eligible for GAVI Alliance support (Uzbekistan). METHODS AND FINDINGS: A decision analytic model was used to estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other types of Hib disease with and without the vaccine. Treatment costs were attached to each disease event. Data on disease incidence, case fatality ratios and costs were primarily determined from national sources. For the Belarus 2009 birth cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases, 34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted DALY averted are US$ 9,323 in Belarus and US$ 267 in Uzbekistan. CONCLUSION: The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden. Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus. However, when seen in the context of the relative ability to pay for public health, the vaccine can be considered cost-effective in both countries.

Rapid assessment of Hib disease burden in Vietnam.

BACKGROUND: Several 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. METHODS: Laboratory, 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. RESULTS: We 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. CONCLUSIONS: In 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.

[Epidemiology of Haemophilus influenzae meningitis in Tunisia]. / Epidémiologie des méningites à Haemophilus influenzae en Tunisie.

The incidence of Haemophilus influenzae b meningitis (Hib) in children < 5 years in Tunisia was studied through a surveillance system set up in June 2000 and followed for 14 months. Population-based surveillance began in 3 governorates and sentinel surveillance in 2. Children < 5 years suspected of meningitis had lumbar puncture, macroscopic exam, blood count, chemical analysis and culture carried out. In the 14 months, 80 cases of meningitis were recorded. From the population-based surveillance most cases were children < 1 year (73.6%) and boys (64%). H. influenzae was isolated in 38% of cases, pneumococci in 13% and meningococci in 7%. The incidence of confirmed Hib was 14.4/100 000 children. The estimated cost of identifying and treating Hib meningitis and its complications was greater than the cost of vaccine introduction. Based this study, the Ministry of Health has decided to introduce Hib vaccination.

Haemophilus influenzae type b infection in children in Pacific countries.

The Haemophilus influenzae type b (Hib) disease burden among children under five years in four Pacific island countries (PIC was estimated. The incidence of confirmed Hib meningitis was calculated using numbers of culture confirmed isolates. In addition, the WHO Hib Rapid Assessment Tool (RAT) was used to estimate the true Hib meningitis incidence and the number of Hib meningitis and pneumonia cases and deaths. The Hib meningitis annual incidence in three PICs was 70 to 84 per 100,000 children under five years. The high Hib disease burden and the relative cost-effectiveness of Hib vaccine, make the introduction of Hib vaccine a good investment for PICs costing US$ 1,000-10,000 for each death prevented - ignoring treatment cost savings.

Cost-benefit analysis of a Haemophilus influenzae type b meningitis prevention programme in The Philippines.

BACKGROUND: Haemophilus influenzae type b (Hib) meningitis is associated with high mortality and serious sequelae in children under 5 years of age. Vaccines which can prevent this infection are available. OBJECTIVE: To evaluate the costs and benefits of a 3-dose immunisation schedule in Manila, Philippines. PERSPECTIVE: Government and societal perspectives. DESIGN AND PARTICIPANTS: A cost-benefit analysis based on a birth cohort of 100,000 children. The state of health of the cohort with and without a Hib immunisation programme was modelled over a 5-year period. A survey of medical records of patients with Hib in Manila provided data on the extent and cost of sequelae following infection. INTERVENTION: A 3-dose Hib vaccination programme given at ages 2, 3 and 4 months. RESULTS: The model predicted that vaccinating children against Hib meningitis would prevent 553 cases per year in a birth cohort of 100,000, at a cost of 56,200 Philippine pesos (PHP) [$US1,605; 1998 exchange rate] per case (base case assumptions of 90% vaccine efficacy rate, 95 per 100,000 Hib incidence rate, 85% vaccination coverage). Results from the cost-benefit analyses indicated that the saving to the government would be around PHP39 million ($US1.11 million), and the saving to society would be PHP255 million ($US7.28 million). CONCLUSION: There would be a positive economic benefit for the Philippine government and for the Filipino society if a Hib vaccination programme was introduced in Manila.

Clinical and economic impact of a combination Haemophilus influenzae and Hepatitis B vaccine: estimating cost-effectiveness using decision analysis.

BACKGROUND: Compliance with hepatitis B virus (HBV) vaccine remains suboptimal, despite a recommendation by the Advisory Committee on Immunization Practices of the US Public Health Service that all newborns be vaccinated. Although a combined HBV-Haemophilus influenzae type b (Hib) vaccine may improve acceptance of the HBV vaccine, the clinical and economic consequences of this intervention are uncertain. OBJECTIVES: To compare the health impact and cost-effectiveness of the following 2 immunization strategies: current practice of administering HBV vaccine separately (75% compliance) and Hib vaccine alone or as part of a multivalent vaccine (95% compliance); and strategy of delivering a combined HBV-Hib vaccine (95% compliance). DESIGN: A Markov model simulated the natural history of acute and chronic HBV and Hib disease in a cohort of US newborns. Clinical and economic variables were obtained from published reports. RESULTS: The Hib-related outcomes were the same in both strategies, because the efficacy and compliance with Hib vaccine were assumed to be equivalent in both. A 53% reduction in the number of cases of HBV infection with the combination strategy (n = 8541) was estimated when compared with current practice (n = 18 044), along with 205 fewer HBV-related deaths per 1 million infants. Immunization costs of the combination strategy were $11.5 million higher than for current practice ($108.4 million compared with $96.9 million), whereas the cost of HBV-related disease was $4.0 million lower than in current practice. The incremental cost-effectiveness ratio for the combination strategy was $17700 per year of life saved. CONCLUSION: An HBV-Hib vaccine in US infants yields substantial benefits, with a cost-effectiveness ratio that is lower than that of many commonly used medical interventions.

Bacterial meningitis in the pediatric population: paradigm shifts and ramifications for otolaryngology-head and neck surgery.

Various population-based studies have suggested that the incidence and epidemiology of bacterial meningitis is changing. No studies have been published which examine a sample population of the United States at large. Records of pediatric patients age 5 and under who were treated for bacterial meningitis (n = 470) at all US Army medical facilities between 1986 and 1991 were reviewed. The incidence of bacterial meningitis declined by 75% in the study group during this period. The largest decrease occurred in infants less than 1 year of age. The bacterial organisms isolated most commonly, in decreasing frequency were: Haemophilus influenza type b (HIB), pneumococcal, streptococcal, and staphylococcal. The most dramatic abatement occurred in Haemophilus meningitis following the introduction of HIB vaccinations. Neurologic sequelae were identified in 10% of meningitis survivors. The 2 most common impairments were hearing loss and speech/language delay. Economic modeling demonstrates tremendous savings in health care dollars from the decrease in disease incidence. These changes will have substantial bearing on training programs and practitioners, since the management of neurologic sequelae requires the expertise of multiple subspecialists. In the face of a medical onslaught, once devastating diseases are in retreat.

The burden of Haemophilus influenzae type b disease in Australia and an economic appraisal of the vaccine PRP-OMP.

OBJECTIVES: To estimate the incidence and sequelae of Haemophilus influenzae type b disease (Hib) in the Australian population, and to evaluate the costs and outcomes of a vaccination program using the vaccine PRP-OMP at two, four and 12 months. DESIGN: The evaluation was based on a decision analytic model developed by Merck Sharp and Dohme (Australia) Pty Ltd, to predict the number of children who would contract Hib, and suffer mild or severe sequelae or die as a result. The state of health of a cohort of children was modelled each month over a five-year period. A survey of medical records and interviews with parents of children who contracted meningitis in Western Australia from 1984-1990 was undertaken to provide data on the extent and costs of sequelae. RESULTS: The incidence of Hib among non-Aboriginal Australians under five years of age was estimated as 53 per 100,000, and 460 per 100,000 among Aborigines. In a single year at least 630 children may contract Hib, up to 19 may die, and a further 46 may have neurological damage, this being severe in up to 18 children. The number of deaths could be reduced by 17 per year and a further 25 cases of severe and 16 cases of mild disability could be averted. At a price of $20 per dose, and a 5% discount rate, the expected cost per year of life extended by a vaccination program is $3148. When adjusted for the increased number of years without neurological impairment, the incremental cost per quality adjusted life year (QALY) is $1965. Compared with a single vaccine at 18 months, the incremental cost per additional QALY gained is $5047. A separate analysis of the Aboriginal population showed that the proposed vaccination program would be of significant benefit, leading to a saving of resources.

The retreat of Hemophilus influenzae type B invasive disease: analysis of an immunization program and implications for OTO-HNS.

Hemophilus influenzae type b (Hib) is the most common cause of bacterial meningitis among children under 5 years old. Hib is also responsible for other invasive diseases including epiglottitis, cellulitis, sepsis, pneumonia, and osteomyelitis. A child's cumulative risk of systemic Hib disease during the first 5 years of life is approximately 1 in 200. A polysaccharide Hib vaccine was first marketed in 1985, and newer, more effective conjugated vaccines have been licensed since 1987. Immunization schedules have included increasingly younger children. No studies have been published that analyze the effects of a vigorous immunization program on a sample population representative of the United States at large. Records of pediatric patients ages 5 years and younger who were treated for Hib meningitis or epiglottitis (N = 373) at all U.S. Army medical facilities between 1986 and 1991 were reviewed. The combined incidence of these diseases declined by more than 86% in the study group during this period. The largest decrease occurred in infants less than 1 year old, before vaccines were licensed for use in this group. Meanwhile, the number of cases of bacterial meningitis due to other organisms in this cohort remained unchanged. Economic modeling validates the cost-effectiveness of vaccination. The impact of these preliminary trends on health care systems and otolaryngology-head and neck surgery will be significant. Almost two thirds of Hib disease has involved infants under 15 months old, for whom a conjugated vaccine has been available only since October 1990. The change in disease frequency will have substantial bearing on training programs, because management of neurologic sequelae and the emergent airway require the expertise of otolaryngologists. In the face of medical onslaught, Hib invasive disease is in retreat.

Cost-benefit analysis for the use of Haemophilus influenzae type b conjugate vaccine in Santiago, Chile.

Cost-benefit analyses can be integral to the evaluation of interventions in developing countries. The authors compare the potential benefits to the Chilean Ministry of Health, in terms of treatment costs averted, by prevention of Haemophilus influenzae type b (HIB) invasive disease, with the costs of adding HIB conjugate vaccine to the diphtheria-tetanus-pertussis (DTP) immunization routinely administered to infants. In their basecase model, over a 10-year period (1991-2000), vaccination against HIB will prevent 1,229 cases of HIB invasive disease, including 713 cases of meningitis, 107 of whom would suffer severe, long-term sequelae, and between 29 and 116 deaths. Assuming a cost of US$1 for a full three-dose regimen of vaccine, the benefit/cost ratio of 1.66, with a net discounted savings of over $403,225, illustrates that HIB vaccine can be cost-beneficial. Sensitivity analyses which alter each of the variables in the analysis indicate that if the true incidence of HIB disease is twice the published rate, then three doses of vaccine remains cost-beneficial at US#3.

PIP: Health practitioners reviewed the clinical records of all 6-60 month old children who were treated for meningitis caused by Haemophilus influenzae type b (HIB) in 1989-1990 at Roberto del Rio Children's Hospital in Santiago, Chile, to estimate costs for all phases of meningitis treatment (ambulatory visits, hospitalization, and follow-up). They also estimated annual HIB incidence. They determined the cost of adding HIB conjugate vaccine to the DTP vaccine. They assumed a cost of US$1 for a full 3-dose regimen of vaccine. They then conducted a cost benefit analysis of the use of HIB conjugate vaccine to prevent invasive HIB disease in Santiago. The National Health Service had to pay an average of US$1301/case of HIB meningitis and US$887/case of HIB invasive disease other than meningitis, including pre- and post-hospitalization costs and adjustment for frequency of sequelae. Several factors indicated that the estimates were actually underestimates. For example, the researchers did not take into account herd immunity and the fact that sequelae often do not appear until the children are older. The addition of the HIB conjugate vaccine to the immunization program would prevent at least 1229-3111 cases of HIB invasive disease, disabling sequelae, and deaths during a 10-year period. Further, it would save the National Health Service more than US$403,225. The benefit/cost ratio was 1.66. The researchers changed each of the variables in the cost benefit analysis. These sensitivity analyses revealed that if the true incidence of HIB disease were 2 times greater than the based on reported data, the 3 doses of HIB conjugate vaccine would still have a cost benefit of US$3. These results indicated that adding HIB conjugate vaccine would exert a considerable public health and cost benefit. Cost benefit analyses of vaccines would also prove useful to decision-makers in other developing countries.

Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries.

To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).

[Costs and benefits of vaccination against Haemophilus influenzae type b]. / De kosten en baten van vaccinatie tegen Haemophilus influenzae type b.

In the Netherlands, Haemophilus influenzae type b (Hib) causes invasive disease in hundreds of children every year; meningitis is the most frequent and most severe infection. Children from the age of 6 months can be protected against Hib-diseases by conjugated vaccines. The financial consequences of the introduction of such vaccine into the state vaccination programme are considered in a cost-effectiveness analysis. Some elements in the analysis are still uncertain, such as the price and the schedule and method of administration of the vaccine. Presumably, the costs and benefits will be in balance, if one vaccine dose will cost about 7 US $+ and if the administration can be combined with the present programme of vaccinations against diphtheria, whooping cough, poliomyelitis and tetanus.