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.

Influence of socio-economic inequality measured by the Gini coefficient on meningitis incidence caused by Mycobacterium tuberculosis and Haemophilus influenzae in Colombia, 2008-2011.

Bacterial meningitis is an important cause of infectious neurological morbidity and mortality. Its incidence has decreased with the introduction of vaccination programmes against preventable agents. However, low-income and middle-income countries with poor access to health care still have a significant burden of the disease. Thus, the relationship between the Gini coefficient and H. influenzae and M. tuberculosis meningitis incidence in Colombia, during 2008-2011, was assessed. In this ecological study, the Gini coefficient was obtained from the Colombian Department of Statistics, incidence rates were calculated (cases/1,000,000 pop) and linear regressions were performed using the Gini coefficient, to assess the relationship between the latter and the incidence of meningitis. It was observed that when inequality increases in the Colombian departments, the incidence of meningitis also increases, with a significant association in the models (p<0.01) for both M. tuberculosis (r²=0.2382; p<0.001) and H. influenzae (r²=0.2509; p<0.001). This research suggests that high Gini coefficient values influence the incidence of Mycobacterium tuberculosis and Haemophilus influenzae meningitis, showing that social inequality is critical to disease occurrence. Early detection, supervised treatment, vaccination coverage, access to health care are efficient control strategies.

Haemophilus influenzae type b vaccine impact in resource-poor settings in Asia and Africa.

The Haemophilus influenzae type b (Hib) conjugate vaccine has been administered for almost 20 years in developed countries with remarkable success. More recently, the vaccine has been introduced in resource-poor settings, mainly those in Africa. African countries have documented large declines in Hib-invasive disease following universal vaccine introduction based on evaluation of routine surveillance data. As of 2007, only Mongolia in Asia had introduced the vaccine. Consequently, studies are limited to clinical trials in Bangladesh and Indonesia, and these also demonstrate substantial vaccine impact. Beyond invasive disease, three pivotal trials in Africa and Asia have demonstrated vaccine impact against clinical pneumonia end points. In all settings evaluated, Hib vaccine was shown to be cost effective, although the vaccine is not yet cost saving based on pentavalent vaccine prices in excess of US$3 per dose. Future issues include monitoring for serotype replacement and the effects of the HIV epidemic, evaluating the usefulness of a booster dose or new vaccine schedules and working to lower vaccine prices.

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.

Pharmacodynamic evaluation of meropenem and cefotaxime for pediatric meningitis: a report from the OPTAMA program.

OBJECTIVE: To determine the probability of meropenem (Merrem, AstraZeneca Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. METHODS: A 5,000-patient Monte Carlo simulation in a population of 10-year-old children with meningitis was conducted. Pediatric pharmacokinetic data were derived from the literature. Pathogen minimum inhibitory concentrations (MICs) were obtained from common bacteria that had caused meningitis collected during pediatric clinical trials. Time above the MIC exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or probability of target attainment was defined as 40% and 50% time above the MIC for meropenem and cefotaxime, respectively. High cumulative fractions of responses were defined as >90% probability of target attainment against the populations of bacteria. RESULTS: Meropenem was calculated to achieve 94.7%, 94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H. influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S. pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and 84.8% cumulative fractions of response, respectively. CONCLUSION: In a simulated population of 10-year-old children, meropenem had a high likelihood of attaining bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90% cumulative fraction of response against only N. meningitidis. Therefore, at the doses simulated, meropenem may be a more appropriate empiric choice for the treatment of bacterial meningitis in pediatric patients presumed to be caused by these pathogens until culture and susceptibility data are available.

Rapid assessment tool for Haemophilus influenzae type b disease in developing countries.

Haemophilus influenzae type b (Hib) still causes a substantial number of deaths among children in developing countries, despite the availability of effective conjugate vaccines. A major obstacle in developing a Hib vaccine has been limited awareness about the impact of Hib disease. A tool was developed to estimate the national rates of Hib meningitis and pneumonia by assessing retrospective local data over 7 to 10 days. Data from 11 countries in Africa, the Middle East, and Asia were studied and showed rates of Hib meningitis from >50 cases per 100,000 children >5 years in Ghana and Uganda to <15 per 100,000 in Iran, Jordan, and Uzbekistan. Results were affected by the quality of available data. The Hib rapid assessment tool can be useful to countries that desire a timely assessment of Hib disease rates.

High incidence of Haemophilus influenzae type b infection in children in Pacific island countries.

The Haemophilus influenzae type b (Hib) disease burden among children <5 years old in 4 Pacific island countries (PICs) was estimated. The incidence of confirmed Hib meningitis was calculated using the numbers of culture-confirmed isolates. In addition, the World Health Organization (WHO) Hib Rapid Assessment Tool (RAT) was used to estimate the true Hib meningitis incidence and the number of Hib meningitis and pneumonia cases, as well as the number of deaths due to Hib meningitis and pneumonia. The Hib meningitis annual incidence in 3 PICs was 70-84 cases per 100,000 children <5 years old. For PICs, the RAT is likely to overestimate the Hib pneumonia burden, as it assumes a 5 : 1 ratio of Hib pneumonia to Hib meningitis. The true ratio is likely to be 1 : 1. 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 US1000 dollars-US10,000 dollars for each death prevented--a number that ignores savings from reductions in the cost of treatment.

Antimicrobial resistance in Haemophilus influenzae isolated during population-based surveillance for meningitis in Salvador, Brazil.

Antimicrobial susceptibility was determined for 150 Haemophilus influenzae isolates obtained during population-based surveillance for meningitis in Salvador, Brazil. Ten (6.7%) isolates were resistant to ampicillin and chloramphenicol. Of these, two isolates, a beta-lactamase and non-beta-lactamase producer, were resistant to amoxacillin-clavulinic acid. These findings indicate that present antibiotic regimens in Brazil may not be appropriate for the treatment of H. influenzae meningitis.

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.