Comparative impact assessment of child pneumonia interventions

Louis Niessen,a Anne ten Hove,b Henk Hilderink,c Martin Weber,d Kim Mulholland e & Majid Ezzati f

Objective To compare the cost-effectiveness of interventions to reduce pneumonia mortality through risk reduction, immunization and case management. Methods Country-specic pneumonia burden estimates and intervention costs from WHO were used to review estimates of pneumonia risk in children under 5 years of age and the efcacy of interventions (case management, pneumonia-related vaccines, improved nutrition and reduced indoor air pollution from household solid fuels). We calculated health benets (disability-adjusted life years, DALYs, averted) and intervention costs over a period of 10 years for 40 countries, accounting for 90% of pneumonia child deaths. Findings Solid fuel use contributes 30% (90% condence interval: 1844) to the burden of childhood pneumonia. Efcacious community-based treatment, promotion of exclusive breastfeeding, zinc supplementation and Haemophilus inuenzae type b (Hib) and Streptococcus pneumoniae immunization through existing programmes showed cost-effectiveness ratios of 1060 International dollars (I$) per DALY in low-income countries and less than I$120 per DALY in middle-income countries. Low-emission biomass stoves and cleaner fuels may be cost-effective in low-income regions. Facility-based treatment is potentially cost-effective, with ratios of I$60120 per DALY. The cost-effectiveness of community case management depends on home visit cost. Conclusion Vaccines against Hib and S. pneumoniae, efcacious case management, breastfeeding promotion and zinc supplementation are cost-effective in reducing pneumonia mortality. Environmental and nutritional interventions reduce pneumonia and provide other benets. These strategies combined may reduce total child mortality by 17%.
Une traduction en franais de ce rsum gure la n de larticle. Al nal del artculo se facilita una traduccin al espaol. .

Introduction
Progress in reducing mortality from pneumonia in children under 5years of age has been relatively slow in many parts of the developing world, where about 155 million clinical pneumonia episodes and 2million deaths occur annually.1,2 Risk factors for pneumonia include stunting and underweight,1,3,4 suboptimal breastfeeding,5,6 lack of immunization7,8 and indoor air pollution from household use of solid fuels.912 There is evidence that effective and appropriate management of clinical cases is possible 13,14 at health-care facilities15 and in the community,16 but this level of management is often lacking. Efforts to control pneumonia are needed to meet Millennium Development Goal4 (MDG4), to reduce child mortality in the world by two-thirds by 2015.17 Often, a package of priority interventions is developed to address MDG targets and reduce child mortality.4,6,1820 Cost-effectiveness analysis has become vital in deciding what interventions to implement and scale up.21 Single-candidate interventions to reduce pneumonia have been evaluated in general economic terms,6,11,18,2224 but no comprehensive analysis has focused on pneumonia control. Different interventions can affect incidence or case fatality, with differences noted across age groups. Population risk interventions can target specific subpopulations, while immu-

nization is intended for all infants. Preventive interventions of this kind may reduce the incidence of pneumonia, whereas case management influences case fatality after falling ill. Both types of interventions can reduce pneumonia mortality. The aim of this study was to compare the impact of eight preventive and curative interventions at the population level 6,2527 and to identify the intervention mixes that generate the highest possible level of child health at the lowest cost.

Methods
To estimate the population health effects and total costs of pneumonia interventions from a health-care perspective, we applied demographic life tables for the 40 countries with the highest mortality (list available at: http://oldwww.bmg.eur.nl/ personal/niessen/Webtable%20Countries%20by%20Region. doc The tables were used to estimate the health effect of risk factors, as well as the reductions in incidence and case fatality in population cohorts, simultaneously and consistently.6,2527 Detailed descriptions of concepts, methods, background papers, regional studies and data are available at: WHOCHOICE (CHOosing Interventions that are Cost Effective) at: www.who.int/choice/en. Box1 provides an overview of the approach.

Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD, 21205, United States of America (USA). Department for Health Policy and Management, Erasmus University, Rotterdam, the Netherlands. c Netherlands Environmental Assessment Agency, Bilthoven, the Netherlands. d World Health Organization Country Ofce, Jakarta, Indonesia. e Infectious Disease Epidemiology Unit, London School of Hygiene, London, England. f Department of Population and International Health and Department of Environmental Health, Harvard School of Public Health, Cambridge, MA, USA. Correspondence to LW Niessen (e-mail: lniessen@jhsph.edu). (Submitted: 24 January 2008 Revised version received: 1 October 2008 Accepted: 2 October 2008 Published online: 16 April 2009 )
a b

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We considered the epidemiological characteristics and level of health care of each of the 40 countries, as well as the coverage levels of the expanded programme on immunization (EPI) and of facility-based case management. Due to the large uncertainties involved in the epidemiologic, effectiveness and cost estimates, we included a high and a low cost-effectiveness scenario for each mix of interventions. Each countrys life table provides summary estimates of how pneumonia affects mortality and morbidity, expressed in terms of disability-adjusted life years (DALYs) lost. The tables also provide estimates of the effect and cost of mixed health interventions, in United States dollars (US$) for the year 2000, with a 3% discount rate according to health economics guidelines. We combined estimated health gains and costs per intervention to identify the sets of health interventions that maximized child health at different budget levels by providing the greatest health yield per dollar spent. The life tables were implemented in C++ (a general programming language) using Mlanguage (a language for working with data and building domain models). The script with M-equations is available at: http:// oldwww.bmg.eur.nl/persona/niessen/ GAPP_LOW.MPdf.pdf

Box 1. Stepwise description of impact assessment for comparatively analysing the costs and effects of interventions 6,25,26 1. Construct epidemiologic disease model. Give a population-based description; establish how parameters of the disease model interact (i.e. relative risks, incidence, case-fatality ratio, neonatal and mortality rates, by age group and sex); 2. Review national data for year of study. Include population structure and absolute gures, births, pneumonia epidemiologic rates and intervention coverage; 3. Construct baseline epidemiological parameters . Reect current population gures and epidemiologic rates, a situation of limited health care and the future United Nations demographic scenario; 4. Estimate effectiveness. Repeat analysis under Step 3 with changes to one or more key epidemiological parameters (incidence or casefatality rate) as a result of intervention effectiveness; compute the total number of healthy life years gained (or of DALYs averted). 5. Estimate costs. Establish coverage and contact rates; apply unit costs and add programme costs by intervention mix. 6. Generate a cost and effectiveness league table. Estimate the total costs and health benets (DALYs averted) of single interventions and intervention mixes and establish a ranking table based on the cost-effectiveness ratio.
DALY, disability-adjusted life year.

Epidemiologic and demographic data

The life tables used in the model were based on the recently published WHO country data, which draw on reviews of incidence and mortality for childhood and neonatal pneumonia. Incidence estimates were taken from the epidemiological review.1 Consistent applied case-fatality rates were calculated by dividing annual incidence figures by annual mortality rates from the global burden of disease data set.2,7 Risk factor prevalence data were derived from the WHO Statistical Information System (WHOSIS), available at: http://www.who.int/whosis/en/ index.html They included nonexclusive breastfeeding, undernutrition (defined as underweight for age, z<2), measles immunization coverage and exposure to indoor air pollution in the population under 5years of age. Relative risks of indoor air pollution by type of biomass fuel for pneumonia incidence were de-

rived from the Global Action Plan for Pneumonia (GAPP).9,10,28 Other relative risks for pneumonia incidence were obtained from the same review.1 National statistics on neonatal, infant and child mortality for 2005 were obtained from the online database of the Institute for Health Metrics and Evaluation.7 The fractions of neonatal mortality attributable to pneumonia and sepsis were obtained from the The Lancet nutrition series.20 Case-fatality ratios for children are specified by three age groups: neonatal period until 1month of age, remainder of the first year (212 months of age) and 15 years. The disability weight used to compute pneumonia morbidity for a disease episode lasting 2weeks was 0.279.29 DALYs were calculated by applying the region-specific disability weights for the general population by age and sex.30 Country-level demographic data on population structure, birth rates and general mortality rates were obtained from official 2005 estimates by the Population Reference Bureau (available at: http://www.prb.org/Publications/ Datasheets/2008/2008wpds.aspx).

CHOICE project.6 The calculations included the extra life-years lived by additional surviving children beyond the 10-year period, as well as the pneumonia incidence reduction from immunization until the last immunized age group reaches the age of 5years (in 2020). We estimated total health effects over a period of 100 years to include all life-years gained beyond the 10-year time horizon, among all survivors. We calculated intervention costs in International dollars (I$) to allow comparisons. Table1 shows the selected interventions and related input data for various scenarios. The subsections below describe the scenario assumptions by intervention category. Reduction of indoor air pollution The 90% confidence interval (CI) of the relative risk (RR) of pneumonia due to exposure to indoor air pollution was estimated to be 1.42 to 2.53.28 Two interventions for indoor air pollution were selected.9,28 The first was a switch at the household level to cleaner gaseous or liquid fuels (liquefied petroleum gas, kerosene or ethanol); the second was better combustion ventilation through high-quality and well-maintained biomass stoves. The health effect of intervening against this risk factor derives primarily from observational studies (including one unpublished randomized study of high-quality stoves). The GAPP reviews assumed that introducing cleaner fuel reduces pneumonia risk.9,28 Based on this assumption, changing to full-scale cleaner household fuel could
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Interventions, effectiveness andcosts

In all scenarios we assumed a programme effectiveness time horizon of 10 years for all interventions, starting in 2005. After that, the new population cohorts resumed pre-intervention status, in line with the standardized cost-effectiveness approach of WHO-

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Table 1. Input data for pneumonia intervention effectiveness, estimated health care costs and literature sources, 2005 Code Intervention Indoor air pollution Liquid fuel stoves Improved solid fuel stoves Nutrition Breastfeeding promotion Zinc supplementation Immunization Pneumococcal conjugate Haemophilus inuenzae type B Case management Community-based Facility-based Effectiveness a low-highscenariorange RR-based exposure reduction [formula: (1(1RR l ) b )(1(1RR h ) c )] RR-based exposure reduction 75% inspecic settings 1523% reduction in infants 1425% (90% CI: 830) reduction Effect level Source Costs of intervention low-highscenario range I$ 8.5714.47 in AMR D d per household member, per year I$ 4.827.59 in AMR D d per household member, per year I$ per child I$ per child Source

E1 E2

Incidence Incidence

23

23

N1 N2

Incidence Incidence

3,6

WHO dataset e WHO dataset e

24

3,6,30

I1 I2

2335% reduction 2234% reduction

Incidence Incidence

I$ 1964 per immunized child I$ 5.839.69 per immunized child 12 visits of I$ 2.139.40 per incident case I$ per child

22

C1 C2

3450% (90% CI: 2257) for neonatalpneumonia 2945% (90% CI: 2049)

Case fatality Case fatality

13,16,31

14

32

WHO dataset e

AMR, WHO Region of the Americas; CI, condence interval; I$, International dollar; RR, relative risk (values from review).28 a Age-specic reductions in exposure among all age groups under 5 years, unless otherwise indicated. b RRl is the relative risk of pneumonia under low exposure (1.42 in this study). c RRh is the relative risk of pneumonia under high exposure (2.53 in this study). d High-tech and low-tech liquid fuel stoves were considered, as well as an improved stove for solid fuels.23 For the latter, we assumed a 2-year (high-cost scenario) and a 4-year (low-cost scenario) average lifetime. Cost data are WHO-region specic. e WHO-CHOICE (CHOosing Interventions that are Cost Effective) dataset for child survival interventions (http://www.who.int/choice/en), November 2007. Data are WHO-region specic.

lower pneumonia incidence by 50% (the attributable burden for indoor air pollution). However, high-quality, well-maintained stoves are not expected to prevent all exposure to indoor air pollution. In an earlier review and costeffectiveness study, a 75% reduction in exposure was assumed in a scenario of full coverage with good stoves.11 Given the high and low RRs linked to indoor air pollution under this scenario (equations in Table1), the pneumonia incidence reduction would be 22.2% to 45.8%. 28 The cost methodology and actual cost estimates are based on WHO reports 11,23 with a two- or fouryear stove lifetime. Nutritional interventions Selected nutritional interventions to reduce pneumonia were exclusive breastfeeding promotion up to 6months of age 6,18 and food supplementation with zinc.3,33 Region-specific cost estimates were based on those from the WHOCHOICE programme.
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Immunizations The scenarios included two vaccines as potential interventions to reduce pneumonia risk. The measles vaccine was not included, since its already high coverage in most of the 40 countries studied would have made its effect on pneumonia mortality difficult to quantify. The population effectiveness of immunization depends on the level of protection against the bacteria (Hib and pneumococcus), but even more on the actual attributable contribution of these bacteria to the pneumonia burden. Hib and pneumococcus may account for more than half of pneumonia mortality in children.17 The relative importance of these bacteria as causes of pneumonia in different settings is unknown, but the similarity of the trial results suggests that major differences between populations do not exist. The effectiveness range given by the high and low country scenarios takes into account the variety of agents (Table1). The joint effect of the two vaccination

programmes targeting two different microorganisms was assumed to be additive. The cost estimates were based on earlier economic evaluations.22,24 Implementation was assumed to occur within existing immunization programmes and infrastructure. Pneumonia case management Two delivery strategies were chosen to treat children with pneumonia: a facilitybased approach,15 and a communitylevel approach in which children were diagnosed and treated by community health workers.16 The estimated reduction of pneumonia mortality through pneumonia case managementwas basedon two reviews.13,16 These reported an efficacious (i.e. under ideal circumstances) reduction of 42% (90% CI: 2257) in neonatal pneumonia mortality and of 36% (90% CI: 2049) in child pneumonia mortality, confirmed by a review of management by community health workers.31 We subtracted these expected reductions from the

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Table 2. Population using solid fuels, and PAR for pneumonia mortality among children <5 years of age, by WHO subregions, 2005 WHO subregion a AFR D AFR E AMR A AMR B AMR D EMR B EMR D EUR A EUR B EUR C SEAR B SEAR D WPR A WPR B Residual World Population Population using solid fuels No. 304 199 839 338 409 271 325 897 888 435 563 238 70 637 557 137 098 168 346 537 669 413 765 659 218 138 441 242 471 330 290 459 728 1 246 955 684 154 258 746 1 532 885 216 11 915 069 6 069 193 503 211 063 296 273 010 077 18 074 771 57 197 830 28 599 404 11 394 365 175 005 075 21 062 657 55 160 415 19 684 368 208 138 629 951 016 609 7 898 007 1 137 968 143 2 770 500 3 178 044 147 % 69 81 6 13 40 8 51 5 25 8 72 76 5 74 23 52 PAR b (%) (basedon RR c=1.80) 36 39 4 10 24 6 29 4 17 6 36 38 4 37 16 30 PAR b (%) (basedon RR c=1.42) 23 25 2 5 15 3 17 2 10 3 23 24 2 24 9 18 PAR b (%) (basedon RR c=2.53) 51 55 8 17 38 11 44 7 28 11 52 54 7 53 26 44

CI, condence interval; PAR, population-attributable risk; RR, relative risk. a AFR, WHO African Region; AMR, WHO Region of the Americas; EMR, WHO Eastern Mediterranean Region; EUR, WHO European Region; SEAR, WHO South-East Asia Region; WPR, WHO Western Pacic Region. WHO regions are subdivided based on child and adult mortality: A, very low child and very low adult mortality; B, low child and low adult mortality; C, low child and high adult mortality; D, high child and high adult mortality; E, high child and very high adult mortality. A list of countries in WHO subregions is available at: http://www.who.int/choice/demography/regions b Based on [P (RR 1)] / [(P (RR 1) + 1] where P is risk prevalence and RR is the relative risk related to the exposure to solid fuel use.2,25 The calculations include 90% CIs for the RR of pneumonia (based on the aggregate of 40 high-burden countries). c The RR value range is based on the systematic review.28

country-specific, age-specific case fatality rates, while we included the uncertainty range based on the CI. In severe cases (8.6% of all incident cases), we assumed a case fatality reduction of 51%.32 The cost data of case-management strategies at the facility level are from the WHOCHOICE programme and updates by WHOs Child and Adolescent Health Department.21,32 The community-based cost estimates are from the Disease Control Priorities in Developing Countries (DCP2) project.14 We varied the number of budgeted visits by a village agent to children treated for pneumonia by one (low-cost scenario) to two times (highcost scenario).14,31

Table 3. High and low estimates of child mortality reduction for two pneumonia intervention packages for 40 countries clustered by WHO subregion WHO subregion a AFR D AFR E AMR B AMR D EMR D SEAR B SEAR D WPR B C1, N1, N2, I1, I2 package High b 10.7 14.7 8.6 8.6 14.4 7.1 8.5 9.1 Low b 7.8 10.8 6.3 6.3 10.5 5.2 6.1 6.7 E1, C1, N1+2, I1+2 package High b 12.9 17.3 9.8 9.8 17.0 8.2 10.3 10.3 Lowb 9.5 13.2 7.3 7.3 12.7 6.2 7.5 7.9

Results
Table2 shows the regional aggregate results on the effect of using solid fuels on pneumonia mortality in children. Table3 shows the potential impact of pneumonia interventions on total mortality among children under5, and Table4 lists the cost-effectiveness ratios. In each table, all eight intervention options are grouped into the four intervention areas described above (indoor air pollution, undernutrition,

C1, case management community-based; E1, use of cleaner liquid fuels; I1, pneumococcal vaccine; I2,Haemophilus inuenza type B vaccine; N1, breastfeeding promotion; N2, zinc supplementation. a AFR, WHO African Region; AMR, WHO Region of the Americas; EMR, WHO Eastern Mediterranean Region; SEAR, WHO South-East Asia Region; WPR, WHO Western Pacic Region. WHO regions are subdivided based on child and adult mortality: A, very low child and very low adult mortality; B, low child and low adult mortality; C, low child and high adult mortality; D, high child and high adult mortality; E, high child and very high adult mortality. A list of countries in WHO subregions is available at: http://www.who.int/ choice/demography/regions b The low and high gures are based on the low and high scenario input values in Table1.

immunization and case management). In the country profiles, further expansion of pneumonia programmes is considered, alongside existing vaccination programmes and curative services. The attributable pneumonia burden due to indoor air pollution by

WHO region was based on the countryspecific exposure estimates from the WHOSIS database. The two countries with the largest populations China and India showed a high level (>70%) of solid fuel use. The attributable burden for indoor air pollution in world
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Table 4. High and low cost-effectiveness estimates (I$ per DALY averted) of single interventions to reduce pneumonia mortality, for 40 countries clustered by WHO subregion WHO subregion a SEAR B SEAR D WPR B AFR D AFR E EMR D AMR D AMR B E1 Low
b

E2
b

N1
b

N2
b

I1
b

I2 High
b

C1 High 407 293 610 69 120 89 245 335

b

C2
b

High

Low

High

Low

High 242 90 407 66 48 63 295 356

Low 66 25 86 12 12 16 18 17

High 105 40 137 19 19 26 28 27

Low

Low

Low

High 274 210 343 65 107 203 330 172

High 780 277 678 62 64 71 492 489

High b 1011 357 879 81 83 92 635 637

1567 8918 930 808 2149 448 3200 17823 1382 107 356 72 232 780 139 135 837 86 467 1572 343 1226 3936 1420

3312 1647 5612 243 498 296 1097 3812

177 67 299 49 35 47 218 261

238 109 266 44 45 50 223 243

1292 593 1447 241 244 273 1207 1324

159 115 238 27 46 35 96 130

90 69 112 21 35 66 108 56

C1, case management community-based; C2, case management facility-based; DALY, disability-adjusted life year; E1, use of cleaner liquid fuels; E2, solid fuel stoves; I1, pneumococcal vaccine; I2, Haemophilus inuenza type B vaccine; I$, International dollar; N1, breast feeding promotion; N2, zinc supplementation. a AFR, WHO African Region; AMR, WHO Region of the Americas; EMR, WHO Eastern Mediterranean Region; SEAR, WHO South-East Asia Region; WPR, WHO Western Pacic Region. WHOregions are subdivided based on child and adult mortality: A, very low child and very low adult mortality; B, low child and low adult mortality; C, low child and high adult mortality; D, high child and high adult mortality; E, high child and very high adult mortality. A list of countries in WHO subregions is available at: http://www.who.int/choice/demography/regions b The low and high cost-effectiveness gures are based on the low and high scenario input values in Table1.

regions varied from 10% to 38%, with a limited uncertainty range. The contribution of indoor air pollution to the global burden of childhood pneumonia is large (30%; CI: 1844). Table3 provides the aggregated results by WHO region of health gains for two intervention packages in the high-burden countries. Table5, which illustrates the possibilities for country-level policy-making, presents two country profiles with combinations of eight intervention scenarios. Both single (Table4) and combined interventions (Table5) show low-cost outcomes between I$10 and I$60 per DALY averted for interventions in the WHO Africa D and E subregions, and in the WHO Eastern Mediterranean D subregion. In other regions, effective options were immunization, nutritional interventions and community-based case management. A listing of WHO epidemiological subregions is available at: http://www. who.int/choice/demography/regions Many mixes of interventions fell in the cost range of I$60 to I$120 per DALY averted; others were less cost-effective in light of the general country income level. In some poorer regions, the two indoor air pollution interventions showed the same cost-effective levels as other interventions. In general, the indoor air pollution interventions appear to be less cost-effective than other interventions for reducing pneumonia mortality. The maximum potential reduction in child mortality, given
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existing infrastructures and including indoor air pollution interventions, appears to be about 1317%. Thus, most of the child pneumonia mortality could be avoided if all interventions were implemented.

Discussion
Population-based preventive measures and expanding community-based case management appear to be the most effective options for reducing pneumonia mortality. Adding these measures to existing facility-based case management would increase the efficiency of health system as a whole. When outreach expansion is limited and infrastructure is lacking, immunization is costly. Where measles vaccination coverage is already high, both types of pneumonia vaccine are attractive options. The estimates on immunization depend strongly on the price per dose. Expanded case management, combined with expanded use of new vaccines, would increase system efficiency further. Adding new vaccines and expanding immunization coverage, nutritional interventions and community case management lead to relatively cost-effective pneumonia packages, as compared with facility-based management alone, because the latter was more costly in all scenarios. Additionally, we found that health risk reduction through nutritional and immunization intervention programmes increases the cost-effectiveness of programmes for case management

of childhood illnesses. The region and country league tables present the additional cost-effective options of expanded community case management and improved neonatal management. The cost-effectiveness results showed the efficiency of implementing interventions alongside an existing health care structure, in comparison with a baseline situation. Presenting the results in this way provides policymakers with a general impression of the impact of an intervention; it also makes it possible to compare the efficiency of existing and new packages and possible ways to improve the allocation of funds. For example, in a country such as Guatemala, the most attractive additional options would be zinc supplementation combined with community case management. If these interventions were introduced simultaneously with the available environmental interventions, the additional cost of the package per DALY would increase. When environmental interventions are introduced wherever other interventions are already in place, the extra health benefits are limited and the additional cost per DALY (i.e. marginal cost-effectiveness) can be high. For example, in a country such as Nigeria, which has some infrastructure but no proven options to reduce indoor air pollution, including up-scaling community case management, along with preventive programmes, would increase the cost-effectiveness of implementing a pneumonia control package.

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Table 5. Impact of pneumonia interventions: population costs and health effects of intervention mixes, ranked by costeffectiveness ratio Scenario Low a Guatemala N2 C1 + N2 N2 + I2 C1 + N2 + I2 I2 C1 + I2 C1 N2 + I1 + I2 C1 + N2 + I1 + I2 C1 + I1 + I2 I1 + I2 N1 + N2 + I1 + I2 C1 + N1 + N2 + I1 + I2 N1 I1 E2 + N1 + N2 E2 + N1 + N2 + I1 + I2 E1 + N2 + I1 + I2 E2 C1 + N1 + N2 + E1 + I1 + I2 I1 + C2 E1 + N1 + N2 + I1 + I2 E1 C2 Nigeria N2 C1 C1 + N2 C1 + I2 C1 + N2 + I2 N2 + I2 I2 C1 + N2 + I1 + I2 C1 + I1 + I2 N2 + I1 + I2 C1 + N1 + N2 + I1 + I2 I1 + I2 N1 + N2 + I1 + I2 E2 + N1 + N2 I1 E2 + N1 + N2 + I1 + I2 E2 E1 + N2 + I1 + I2 C1 + N1 + N2 + E1 + I1 + I2 C2 I1 + C2 E1 + N1 + N2 + I1 + I2 E1 N1 3 388 548 14 456 120 22 947 950 32 557 260 19 556 400 30 645 650 12 771 920 69 744 980 77 836 540 75 686 320 66 348 560 92 885 300 100 765 800 23 128 920 46 777 990 102 294 300 168 673 800 207 344 100 75 765 250 236 928 300 105 490 400 230 488 000 137 565 200 58 702 570 128 164 700 168 511 300 274 758 000 258 060 800 365 650 800 227 851 200 99 643 700 608 643 400 499 627 700 479 963 200 831 553 600 351 680 200 706 739 500 1 019 693 000 251 974 300 1 371 835 000 664 495 100 1 800 313 000 2 127 876 000 804 987 900 1 057 172 000 2 027 254 000 1 319 492 000 226 542 300 Cost (I$) High a 3 388 755 22 847 770 35 885 920 51 380 010 32 489 570 52 833 210 25 549 410 202 430 400 213 846 400 214 000 500 199 012 700 225 585 800 236 592 300 23 129 580 166 457 900 145 676 800 344 773 400 429 838 300 119 135 400 459 878 300 225 193 400 452 992 500 227 326 900 58 704 310 128 202 800 337 498 200 387 071 600 471 722 200 528 628 400 293 837 000 165 537 400 1 401 358 000 1 336 704 000 1 191 108 000 1 618 765 000 1 062 450 000 1 418 207 000 1 444 036 000 896 624 000 2 507 878 000 1 088 280 000 3 322 043 000 3 669 423 000 805 210 800 1 702 514 000 3 549 299 000 2 128 944 000 226 555 500 Impact (DALYs averted) Low a 94 708 153 759 197 545 247 505 117 737 175 482 68 752 304 660 345 132 286 650 239 878 339 382 376 289 61 849 122 548 223 486 391 775 380 875 96 467 439 383 183 402 409 236 128 460 72 978 3 762 062 5 526 855 8 583 929 7 368 852 10 237 650 5 713 960 2 173 602 11 960 940 9 288 789 7 748 521 12 606 920 4 450 029 8 546 800 8 300 044 2 263 079 11 689 880 4 275 433 12 097 260 16 001 450 5 870 092 7 765 486 12 738 820 5 706 202 1 067 216 High a 168 753 248 160 310 204 370 709 181 722 261 407 105 082 455 961 496 946 422 480 368 496 489 399 525 116 94 573 187 061 369 041 557 602 559 431 196 759 602 671 266 837 580 330 262 222 106 185 6 731 571 8 480 821 13 260 480 11 046 040 15 369 100 9 466 567 3 366 076 17 543 130 13 691 530 12 287 710 18 236 400 6 849 750 13 268 470 14 377 170 3 465 493 18 402 300 8 763 258 19 531 300 23 081 510 8 570 428 11 202 330 20 116 860 11 697 470 1 642 060 Cost-effectiveness (I$ per DALY averted) Low 20 58 74 88 108 117 122 153 157 179 180 190 192 245 250 277 302 371 385 393 395 397 525 553 19 20 21 23 24 24 30 35 36 39 46 51 53 71 73 75 76 92 92 94 94 101 113 138 High 36 149 182 208 276 301 372 664 620 747 830 665 629 374 1 358 652 880 1 129 1 235 1 047 1 228 1 107 1 770 804 34 61 45 64 52 51 76 117 144 154 128 239 166 174 396 215 255 275 229 137 219 279 373 212

C1, case management community-based; C2, case management facility-based; DALY, disability-adjusted life year; E1, use of cleaner liquid fuels; E2, use of solid fuel stoves; I1, pneumococcal vaccine; I2, Haemophilus inuenza type B vaccine; I$, International dollar; N1, breastfeeding promotion; N2, zinc supplementation. a The low and high cost-effectiveness gures are based on the low and high scenario input values in Table1. Bull World Health Organ 2009;87:472480 | doi:10.2471/BLT.08.050872 477

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Data are limited in almost all countries. Detailed data on pneumonia deaths are lacking, and communitybased data on clinical episodes are sparse.1 Research is needed to better diagnose pneumonia and identify it as the cause of death. Our results are therefore difficult to validate beyond the recent reviews presented, whose quality determines the results of the economic impact evaluation. We were unable to distinguish between studies that reported intervention efficacy and those that reported community effectiveness. We attempted to consider this issue and other sources of uncertainty in our high and low effectiveness and cost scenarios; however, better data on community effectiveness and associated costs are needed. New preventive interventions may lead to net cost savings by preventing costly disease. However, we did not take into account potential savings due to cost offsets, lower use of health services and averted loss of workdays due to fewer illness episodes. Our results are thus conservative. A point of debate is the cost of investing in cleaner fuels, whose cost per DALY averted is higher than that of other options. The results are not directly comparable, however, because the cost of cleaner fuels is offset by other societal benefits, such as time saved looking for firewood or other biomass fuels. If only the additional implementation efforts in an already existing health sector setting are considered and the extra costs of clean fuels are ignored, the cost-effectiveness ratio

is lower. Uncertainty also surrounds the effectiveness and cost of community case management programmes. These are likely to be directly correlated with the quality improvements and the additional cost per village of visits by a village agent. These variables make it difficult to draw definite conclusions from the economic evaluation of these interventions. Still, our studies have identified three potentially valuable interventions to improve child survival: nutritional interventions, immunization and low-cost, effective case management. Innovative use of vaccines, focusing on the highest at-risk groups, could amplify the impact.

National priorities
Donors and national agencies involved in child survival programmes need to select those that maximize child health after considering existing mortality levels, infrastructure and funds available.34 The present study, focused on children, offers policy-makers a range of potential pneumonia interventions and estimates of the money they require.35 Internationally, there is agreement on using disease-burden estimates and data on the cost-effectiveness of interventions to select priority areas. New insights should be applied in real-life country settings to find local solutions and implement appropriate options. Country programme managers need more specific information on the effects and costs of child programmes so they can weigh them against other

criteria, such as equity and other societal benefits.3537 We included in our scenarios only interventions for which effectiveness data were available. Due to a lack of data we could not examine the management of severe malnutrition through improved complementary feeding or strong community programmes. Malnutrition is a major risk factor for severe pneumonia,1 yet no adequate study of the preventive effectiveness of such programmes has been performed. The links between evidence and policy tend to be weak because national policies are the outcome of complicated processes among parties with different interests.36,37 Impact analysis strengthens the selection of optimum child packages, and this paper shows how policy in this area can be more evidence based. Acknowledgements We thank the two anonymous reviewers for their detailed comments, and the members of the Global Action Plan for Pneumonia review groups for their scientific contributions. We also thank Shamim Qazi for his coordinating efforts and support. Funding: The research is supportedby a grant from the Netherlands Environmental Assessment Agency on integrated modelling, while two expert workshops were funded by WHO and the United Nations Childrens Fund. Competing interests: None declared.

Rsum
Evaluation comparative des impacts des interventions contre la pneumonie chez lenfant
Objectif Comparer les rapports cot/efcacit dinterventions pour diminuer la mortalit par pneumonie travers la rduction desrisques, la vaccination et la prise en charge des cas. Mthodes Nous avons utilis des estimations tablies par lOMS pour la charge de pneumonies par pays et les cots des interventions an danalyser les estimations du risque de pneumonie chez les enfants de moins de 5 ans et lefcacit dun certain nombre dinterventions (prise en charge des cas, vaccinations en rapport avec la pneumonie, amlioration de la nutrition et rduction de la pollution de lair intrieur due aux combustibles solides mnagers). Nous avons calcul les bnces pour la sant [annes de vie corriges de lincapacit (DALY) vites] et les cots des interventions sur une priode de 10 ans pour 40 pays totalisant 90 % des dcs denfants par pneumonie. Rsultats Lutilisation de combustibles fossiles contribue pour
478

30%(intervalle de conance 95%: 18-44) la charge de pneumonie infantile. Le traitement efcace au niveau communautaire, la promotion de lallaitement exclusif, la supplmentation en zinc et les vaccinations contre Haemophilus inuenzae type B (Hib) et Streptocccus pneumoniae par le biais des programmes existants ont prsent des rapports cot/efcacit de $ int. 10 $ int. 60 par DALY dans les pays faible revenu et infrieurs $ int. 120 par DALY dans les pays revenu moyen. Lutilisation de fourneaux biomasse faible mission et de combustibles plus propres pourrait offrir un rapport cot/efcacit satisfaisant dans les rgions faible revenu. Le traitement en tablissement de soins pourrait galement fournir un bon rapport cot/efcacit, situ entre $ int. 60 et 120 par DALY. Le rapport cot/efcacit de la prise en charge des cas au niveau communautaire dpend du cot des visites domicile.
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Research
Louis Niessen et al. Assessment of childhood pneumonia interventions

Conclusion La vaccination contre Hib et S. pneumoniae, la prise en charge efcace des cas, la promotion de lallaitement maternel et la supplmentation en zinc sont des interventions prsentant un bon rapport cot/efcacit dans la rduction de la mortalit

par pneumonie. Les interventions dordre environnemental et nutritionnel font rgresser la pneumonie et procurent dautres bnces. La combinaison de ces stratgies peut permettre une rduction globale de la mortalit infantile de 17%.

Resumen
Evaluacin comparativa del impacto de las intervenciones contra la neumona en la niez
Objetivo Comparar la costoecacia de las intervenciones tendentes a reducir la mortalidad por neumona mediante la reduccin del riesgo, la inmunizacin y el manejo de casos. Mtodos Partiendo de estimaciones de la carga de neumona por pases y del costo de las intervenciones segn la OMS, se analizaron las estimaciones del riesgo de neumona entre los menores de 5 aos y la ecacia de las intervenciones (manejo de casos, vacunas relacionadas con la neumona, mejoras de la nutricin y reduccin de la contaminacin del aire en locales cerrados por combustibles slidos domsticos). Calculamos los benecios para la salud (aos de vida ajustados en funcin de la discapacidad -AVAD- evitados) y el costo de las intervenciones a lo largo de 10 aos para 40 pases, abarcando el 90% de las defunciones por neumona en la niez. Resultados El uso de combustibles slidos contribuye en un 30% (intervalo de conanza del 90%: 1844) a la carga de neumona en la niez. Un tratamiento comunitario ecaz, la promocin de la lactancia natural como alimentacin exclusiva, la administracin de suplementos de zinc y la inmunizacin contra Haemophilus inuenzae tipo b (Hib) y Streptococcus pneumoniae a travs de los programas existentes mostraron unas relaciones costo-ecacia de 1060 dlares internacionales (I$) por AVAD en los pases de ingresos bajos, y de menos de I$120 por AVAD en los pases de ingresos medios. Las estufas de biomasa de baja emisin y unos combustibles ms limpios pueden ser costoecaces en las regiones de ingresos bajos. La administracin de tratamiento en servicios de salud es una opcin potencialmente costoecaz, puessupone I$60120 por AVAD. La relacin costo-ecacia del manejo de casos comunitario depende del costo de las visitas domiciliarias. Conclusin La vacunacin contra Hib y S. pneumoniae, el manejo ecaz de los casos, la promocin de la lactancia natural y la administracin de suplementos de zinc son medidas costoecaces contra la mortalidad en la niez. Las intervenciones ambientales y nutricionales reducen la neumona y reportan tambin otros benecios. La combinacin de estas estrategias puede reducir en total la mortalidad en la niez en un 17%.

B 60 10 120 . 120 60 . . : B . .%17

: . : ) ) .( ( %90 40 10 . %30 : .(44 18 %90 )

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Research
Assessment of childhood pneumonia interventions Louis Niessen et al.

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