Global use of Haemophilus influenzae type b conjugate vaccine.

Haemophilus influenzae type b (Hib) conjugate vaccines have been underutilized globally. We report progress in global use of Hib vaccines included in national immunization schedules. The number of countries using Hib vaccine increased from 89/193 (46%) in 2004 to 158/193 (82%) by the end of 2009. The increase was greatest among low-income countries eligible for financial support from the GAVI Alliance [13/75 (17%) in 2004, 60/72 (83%) by the end of 2009], and can be attributed to various factors. Additional efforts are still needed to increase vaccine adoption in lower middle income countries [20/31 (65%) by the end of 2009].

Methodology and measurement of the effectiveness of Haemophilus influenzae type b vaccine: systematic review.

The use of the highly effective Haemophilus influenzae type b (Hib) conjugate vaccine has increased globally. We review the benefits and limitations of studies measuring Hib vaccine effectiveness (VE). We critically examine the case-control approach by assessing the similarities and differences in methodology and findings and discuss the need for future Hib VE studies. In the absence of good surveillance data, vaccine effectiveness studies can play an important role, particularly with the increasing use of pneumococcal vaccine that has not been well tested under field conditions in less developed countries. However, the effectiveness of Hib vaccine has been well documented so the need for future VE Hib studies is minimal.

A systematic review and critical evaluation of invasive Haemophilus influenzae type B disease burden studies in Asia from the last decade: lessons learned for invasive bacterial disease surveillance.

In Asia, questions regarding the burden of Haemophilus influenzae type b (Hib) disease have delayed decision-making on introduction of Hib vaccine. However, over the past decade many studies have been published regarding Hib disease burden in Asia. We conducted a systematic literature review of all reports of Hib disease burden in Asia between 1998 and 2009, and critically reviewed their methods and data quality. We identified 94 studies from 28 countries in Asia presenting data on Hib disease burden. Of the 94 studies reviewed, 49 (52%) used a case definition consistent with World Health Organization standards, and 47 (50%) described laboratory methodology used. Twenty-seven surveillance studies presented data on incidence of Hib disease, with 8 (30%) accounting for missed cases, 6 (15%) accounting for cases with missed diagnostic tests, and 2 (7%) that considered prior antibiotic use. Of the 21 studies that provided incidence data for Hib meningitis, 10 (48%) used active, prospective, population-based surveillance, and found unadjusted incidence rates of Hib meningitis ranging from a low of 0.98 per 100,000 child-years in children aged less than 5 years in China to a high of 28 per 100,000 child-years in children less than 5 years in Mongolia. Of 49 studies that reported the etiology of bacterial meningitis, 30 (60%) identified Hib as the most common cause. This review highlights the importance of using rigorous methodologies, including standardized surveillance methods and appropriate laboratory diagnostic tests, when conducting studies measuring the burden of invasive bacterial diseases including those caused by Hib. When poorly conducted, studies can underestimate disease burden and lead to inappropriate decisions about vaccine introduction.

Haemophilus influenzae type b disease in HIV-infected children: a review of the disease epidemiology and effectiveness of Hib conjugate vaccines.

The paper reviews the literature on the epidemiology of Hib disease and the effectiveness of Hib conjugate vaccine (HibCV) in HIV-infected children. The current three-dose primary Hib conjugate vaccine schedule in low-income settings has had a striking impact on the incidence of Hib disease. However, HIV-infected children have an almost 6-fold higher risk of Haemophilus influenzae type b (Hib) invasive disease than HIV-uninfected children and HibCV effectiveness is lower in this population. HIV-related HibCV failures are difficult to detect without well functioning surveillance systems and HIV testing of cases. Breakthrough Hib cases have been noted in vaccinated HIV-infected children in South Africa. A HibCV booster dose in addition to the three-dose primary schedule is routine in many, but not all, high-income countries. In order to determine whether a booster dose should be given to HIV-infected children in developing countries, well-designed studies need to be conducted to better determine the persistence of protective antibody concentrations, response to booster doses of vaccine as well as timing of and risk factors for vaccine failure in HIV-infected children both treated and naive to antiretroviral drug therapy (ART). Meanwhile, physicians and public health personnel should be especially vigilant at ensuring that HIV-infected infants receive their primary doses of HibCV, ART and co-trimoxazole prophylaxis. Until more definitive evidence is available, physicians may also need to consider a booster dose for such children irrespective of ART status. In any updating of vaccine schedules, HIV-infected children need particular consideration.

The burden of pneumococcal disease among Latin American and Caribbean children: review of the evidence.

OBJECTIVE: To conduct a comprehensive review of data on pneumococcal disease incidence in Latin America and the Caribbean and project the annual number of pneumococcal disease episodes and deaths among children < 5 years of age in the region. METHODS: We carried out a systematic review (1990 to 2006) on the burden of pneumococcal disease in children < 5 years of age in the region. We summarized annual incidence rates and case fatality ratios using medians and interquartile ranges for invasive pneumococcal disease (IPD) (including all-IPD and separately abstracting pneumococcal meningitis, pneumonia, bacteremia, and sepsis data), pneumonia (all cause and radiologically confirmed), and acute otitis media by age group: < 1 year, < 2 years, and < 5 years. We modeled age-specific cumulative incidence of disease obtained from standard Kaplan-Meier analysis and projected data to obtain regional estimates of disease burden. We adjusted burden estimates by serotype coverage, vaccination coverage, and vaccine efficacy to estimate the number of cases and deaths averted. RESULTS: Of 5 998 citations identified, 26 papers from 10 countries were included. The estimated annual burden of pneumonia, meningitis, and acute otitis media caused by pneumococcus in children < 5 years of age ranged from 980 000 to 1 500 000, 2 600 to 6 800, and 980 000 to 1 500 000, respectively. An estimated 12 000 to 28 000 deaths due to pneumococcal disease occur in the region annually. Pneumococcal conjugate vaccine could save 1 life per 1 100 and prevent 1 case per 13 children vaccinated. CONCLUSION: A substantial burden of pneumococcal disease in the region is potentially preventable with pneumococcal conjugate vaccines and should be considered in regional vaccine decision making. Results are limited by the very few studies, conducted in selected settings, included in this review.

The burden of pneumococcal disease among Latin American and Caribbean children: review of the evidence / La carga de enfermedad neumocócica en niños de América Latina y el Caribe: revisión de la información científica

OBJECTIVE: To conduct a comprehensive review of data on pneumococcal disease incidence in Latin America and the Caribbean and project the annual number of pneumococcal disease episodes and deaths among children < 5 years of age in the region. METHODS: We carried out a systematic review (1990 to 2006) on the burden of pneumococcal disease in children < 5 years of age in the region. We summarized annual incidence rates and case fatality ratios using medians and interquartile ranges for invasive pneumococcal disease (IPD) (including all-IPD and separately abstracting pneumococcal meningitis, pneumonia, bacteremia, and sepsis data), pneumonia (all cause and radiologically confirmed), and acute otitis media by age group: < 1 year, < 2 years, and < 5 years. We modeled age-specific cumulative incidence of disease obtained from standard Kaplan-Meier analysis and projected data to obtain regional estimates of disease burden. We adjusted burden estimates by serotype coverage, vaccination coverage, and vaccine efficacy to estimate the number of cases and deaths averted. RESULTS: Of 5 998 citations identified, 26 papers from 10 countries were included. The estimated annual burden of pneumonia, meningitis, and acute otitis media caused by pneumococcus in children < 5 years of age ranged from 980 000 to 1 500 000, 2 600 to 6 800, and 980 000 to 1 500 000, respectively. An estimated 12 000 to 28 000 deaths due to pneumococcal disease occur in the region annually. Pneumococcal conjugate vaccine could save 1 life per 1 100 and prevent 1 case per 13 children vaccinated. CONCLUSION: A substantial burden of pneumococcal disease in the region is potentially preventable with pneumococcal conjugate vaccines and should be considered in regional vaccine decision making. Results are limited by the very few studies, conducted in selected settings, included in this review.

OBJETIVO: Realizar una revisión amplia de los datos sobre la incidencia de la enfermedad neumocócica en América Latina y el Caribe y proyectar el número anual de episodios de la enfermedad y de defunciones entre niños menores de 5 años de edad en la región. MÉTODOS: Se llevó a cabo una revisión sistemática (1990-2006) sobre la carga de la enfermedad neumocócica en niños < 5 años en la región. Las incidencias anuales y las tasas de letalidad se compendiaron mediante las medianas y los rangos intercuartiles de la enfermedad neumocócica invasiva (en su conjunto y por separado para meningitis, neumonía, bacteremia y sepsis neumocócicas), la neumonía (todos los casos confirmados mediante radiología) y la otitis media aguda, por grupos de edad: < 1 año, < 2 años y < 5 años. Se modeló la incidencia acumulada de la enfermedad específica para la edad mediante el análisis estándar de Kaplan-Meier y se proyectaron los datos para obtener estimados regionales de la carga de la enfermedad. Para estimar el número de casos y muertes evitados se ajustaron los estimados de la carga según la cobertura de los serotipos bacterianos, la cobertura de la vacunación y la eficacia de la vacuna. RESULTADOS: De las 5 998 referencias identificadas se seleccionaron 26 artículos de 10 países. La carga anual estimada de neumonía, meningitis y otitis media aguda causadas por neumococos en niños < 5 años varió entre 980 000 y 1 500 000, 2 600 y 6 800, y 980 000 y 1 500 000, respectivamente. Se estimó que en la región podrían morir anualmente entre 12 000 y 28 000 niños debido a la enfermedad neumocócica. La vacuna antineumocócica conjugada podría salvar una vida por cada 1 100 niños vacunados y evitar un caso de enfermedad por cada 13. CONCLUSIONES: Se podría evitar una parte substancial de la carga de enfermedad neumocócica en la región mediante la aplicación de vacunas antineumocócicas conjugadas y esto se debe tener en cuenta al tomar decisiones sobre la vacunación...

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis / Rentabilidad médica de la vacunación antineumocócica en América Latina y el Caribe: un análisis regional

OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

OBJETIVO: En América Latina y el Caribe, la vacunación sistemática de niños contra Streptococcus pneumoniae podría requerir inversiones considerables de los gobiernos y organizaciones donantes. Al evaluar estas inversiones se requiere información sobre los posibles beneficios sanitarios, costos y rentabilidad (relación costo-efectividad) de la vacunación. Se presenta un análisis económico de la vacunación infantil antineumocócica en América Latina y el Caribe a partir de la información de la vacuna y de datos demográficos, epidemiológicos y de costos. MÉTODOS: Se realizó una revisión bibliográfica estructurada previa para llegar a estimados regionales de la incidencia de la enfermedad. Los costos se tomaron de entrevistas a médicos y tarifas públicas. Se construyó un modelo analítico de decisión para comparar la vacunación de los niños de esta región con la vacuna antineumocócica conjugada y la no vacunación, tomando en cuenta solamente el efecto directo de la vacuna en los niños. RESULTADOS: Se proyectó la vacunación antineumocócica con las tasas de cobertura de la vacuna contra la difteria, el tétanos y la tosferina para prevenir 9 500 muertes anuales en menores de 5 años en esta región, o aproximadamente 1 vida salvada por cada 1 100 niños vacunados. Las vidas salvadas y los casos prevenidos de sordera, trastornos psicomotores y convulsiones equivalen a evitar anualmente 321 000 años de vida ajustados por incapacidad (AVAD). A un precio de la vacuna de US$ 5,00 a US$ 53,00 por dosis, el costo por AVAD evitado desde el punto de vista de la sociedad sería de US$ 154,00 a US$ 5 252,00. CONCLUSIONES: La vacuna antineumocócica conjugada fue altamente rentable hasta un precio de US$ 40,00 por dosis. La introducción de esta vacuna en América Latina y el Caribe puede reducir la mortalidad infantil con una alta rentabilidad en un amplio espectro de posibles costos.

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis

OBJECTIVE. In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS. We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine’s direct effects on children. RESULTS. Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted lifeyears (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION. Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis

OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis.

OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004.

BACKGROUND: Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. METHODS: From January 2000 through December 2004, we collected data from Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. RESULTS: We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. CONCLUSIONS: GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.

Restaurant outbreak of Legionnaires' disease associated with a decorative fountain: an environmental and case-control study.

BACKGROUND: From June to November 2005, 18 cases of community-acquired Legionnaires' disease (LD) were reported in Rapid City South Dakota. We conducted epidemiologic and environmental investigations to identify the source of the outbreak. METHODS: We conducted a case-control study that included the first 13 cases and 52 controls randomly selected from emergency department records and matched on underlying illness. We collected information about activities of case-patients and controls during the 14 days before symptom onset. Environmental samples (n = 291) were cultured for Legionella. Clinical and environmental isolates were compared using monoclonal antibody subtyping and sequence based typing (SBT). RESULTS: Case-patients were significantly more likely than controls to have passed through several city areas that contained or were adjacent to areas with cooling towers positive for Legionella. Six of 11 case-patients (matched odds ratio (mOR) 32.7, 95% CI 4.7-infinity) reported eating in Restaurant A versus 0 controls. Legionella pneumophila serogroup 1 was isolated from four clinical specimens: 3 were Benidorm type strains and 1 was a Denver type strain. Legionella were identified from several environmental sites including 24 (56%) of 43 cooling towers tested, but only one site, a small decorative fountain in Restaurant A, contained Benidorm, the outbreak strain. Clinical and environmental Benidorm isolates had identical SBT patterns. CONCLUSION: This is the first time that small fountain without obvious aerosol-generating capability has been implicated as the source of a LD outbreak. Removal of the fountain halted transmission.

Follow-up of a low cost latrine promotion programme in one district of Amhara, Ethiopia: characteristics of early adopters and non-adopters.

OBJECTIVES: To verify reported construction of 22 385 household latrines in 2004, after community mobilization, as part of a trachoma control programme in one district of Amhara, Ethiopia, and to explore characteristics of early latrine adopters and non-adopters. METHODS: We used a two-stage cluster sample survey design to randomly select eight sub-districts and 160 households listed as having built a latrine, and visited them to verify presence and use. Household heads were interviewed to determine latrine cost and knowledge, attitude and practice regarding latrines. Non-latrine adopting neighbours were interviewed for comparison. We estimated district latrine ownership and calculated adjusted odds ratios for factors associated with latrine use. RESULTS: Latrines were present in 87% (95% CI 77-97) of listed households; 90% (81-99) were in use. Among all district residents we estimated ownership as 50.2% (44-56) and use as 45.2% (36-55). Of latrine owners who had built in 2004, 69% (53/77) had spent nothing on their latrine, those who paid spent an average of US$4.0 [standard deviation (SD) US$3.6]; overall the median cost was US$0 and the mean US$0.80 (SD US$1.7). Household heads adopting latrines were 1.9 times (95% CI 1.3-2.8) more likely to have any education and 1.5 times (95% CI 1.1-2.0) more likely to have a larger family than non-adopting neighbours. Cleanliness (48%, 56/116) and health benefits (42%, 49/116) were the most frequently reported advantages of latrines. CONCLUSION: The latrine promotion programme dramatically increased latrine access and use at very low cost. The method of community mobilization used could be an effective way of reaching millennium development sanitation targets.

Equity in resource allocation in the Irish health service. A policy Delphi study.

Resource allocation in the Irish health service, based on historical allocations with incremental increases, is widely believed to be inequitable. Using a three-round policy Delphi survey, which seeks to explore both consensus and disagreement surrounding policy issues, the views of 52 senior health service personnel were sought in order to determine ways to improve equity in resource allocation. Panelists provided several reasons why the current method of resource allocation is inequitable and several suggestions for improving equity. The level of consensus on views was determined by calculating the percentage of ratings in each category based on a series of rating scales. The main suggestion centred around the development and implementation of a needs based resource allocation formula. Panelists reached a high consensus in favour of this but only reached a low consensus as to its feasibility. Potential obstacles identified included methodological difficulties, insufficient resources and resistance from potential losers. These findings highlight concerns about the lack of transparency in the resource allocation process and openness to the development of a more equitable needs based resource allocation model, a move which is becoming more common internationally. Feasibility concerns should not preclude an attempt to begin this process.