Social contact patterns relevant for infectious disease transmission in Cambodia.

Social mixing patterns are key determinants of infectious disease transmission. Mathematical models parameterised with empirical data from contact pattern surveys have played an important role in understanding epidemic dynamics and informing control strategies, including for SARS-CoV-2. However, there is a paucity of data on social mixing patterns in many settings. We conducted a community-based survey in Cambodia in 2012 to characterise mixing patterns and generate setting-specific contact matrices according to age and urban/rural populations. Data were collected using a diary-based approach from 2016 participants, selected by stratified random sampling. Contact patterns were highly age-assortative, with clear intergenerational mixing between household members. Both home and school were high-intensity contact settings, with 27.7% of contacts occurring at home with non-household members. Social mixing patterns differed between rural and urban residents; rural participants tended to have more intergenerational mixing, and a higher number of contacts outside of home, work or school. Participants had low spatial mobility, with 88% of contacts occurring within 1 km of the participants' homes. These data broaden the evidence-base on social mixing patterns in low and middle-income countries and Southeast Asia, and highlight within-country heterogeneities which may be important to consider when modelling the dynamics of pathogens transmitted via close contact.

Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.

BACKGROUND: The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. METHODS: We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. RESULTS: Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. CONCLUSION: Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.

Why cost-effectiveness thresholds for global health donors should differ from thresholds for Ministries of Health (and why it matters).

Healthcare cost-effectiveness analysis is increasingly used to inform priority-setting in low- and middle-income countries and by global health donors. As part of such analyses, cost-effectiveness thresholds are commonly used to determine what is, or is not, cost-effective. Recent years have seen a shift in best practice from a rule-of-thumb 1x or 3x per capita GDP threshold towards using thresholds that, in theory, reflect the opportunity cost of new investments within a given country. In this paper, we observe that international donors face both different resource constraints and opportunity costs compared to national decision-makers. Hence, their perspective on cost-effectiveness thresholds must be different. We discuss the potential implications of distinguishing between national and donor thresholds and outline broad options for how to approach setting a donor-perspective threshold. Further work is needed to clarify healthcare cost-effectiveness threshold theory in the context of international aid and to develop practical policy frameworks for implementation.

Estimating the programmatic cost of targeted mass drug administration for malaria in Myanmar.

BACKGROUND: Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar. METHODS: We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses. RESULTS: The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5. CONCLUSION: This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

Cost analysis of a school-based comprehensive malaria program in primary schools in Sikasso region, Mali.

BACKGROUND: The expansion of malaria prevention and control to school-aged children is receiving increasing attention, but there are still limited data on the costs of intervention. This paper analyses the costs of a comprehensive school-based intervention strategy, delivered by teachers, that included participatory malaria educational activities, distribution of long lasting insecticide-treated nets (LLIN), and Intermittent Parasite Clearance in schools (IPCs) in southern Mali. METHODS: Costs were collected alongside a randomised controlled trial conducted in 80 primary schools in Sikasso Region in Mali in 2010-2012. Cost data were compiled between November 2011 and March 2012 for the 40 intervention schools (6413 children). A provider perspective was adopted. Using an ingredients approach, costs were classified by cost category and by activity. Total costs and cost per child were estimated for the actual intervention, as well as for a simpler version of the programme more suited for scale-up by the government. Univariate sensitivity analysis was performed. RESULTS: The economic cost of the comprehensive intervention was estimated to $10.38 per child (financial cost $8.41) with malaria education, LLIN distribution and IPCs costing $2.13 (20.5%), $5.53 (53.3%) and $2.72 (26.2%) per child respectively. Human resources were found to be the key cost driver, and training costs were the greatest contributor to overall programme costs. Sensitivity analysis showed that an adapted intervention delivering one LLIN instead of two would lower the economic cost to $8.66 per child; and that excluding LLIN distribution in schools altogether, for example in settings where malaria control already includes universal distribution of LLINs at community-level, would reduce costs to $4.89 per child. CONCLUSIONS: A comprehensive school-based control strategy may be a feasible and affordable way to address the burden of malaria among schoolchildren in the Sahel.

Geographic Resource Allocation Based on Cost Effectiveness: An Application to Malaria Policy.

Healthcare services are often provided to a country as a whole, though in many cases the available resources can be more effectively targeted to specific geographically defined populations. In the case of malaria, risk is highly geographically heterogeneous, and many interventions, such as insecticide-treated bed nets and malaria community health workers, can be targeted to populations in a way that maximises impact for the resources available. This paper describes a framework for geographically targeted budget allocation based on the principles of cost-effectiveness analysis and applied to priority setting in malaria control and elimination. The approach can be used with any underlying model able to estimate intervention costs and effects given relevant local data. Efficient geographic targeting of core malaria interventions could significantly increase the impact of the resources available, accelerating progress towards elimination. These methods may also be applicable to priority setting in other disease areas.

Malaria and Economic Evaluation Methods: Challenges and Opportunities.

There is a growing evidence base on the cost effectiveness of malaria interventions. However, certain characteristics of malaria decision problems present a challenge to the application of healthcare economic evaluation methods. This paper identifies five such challenges. The complexities of (i) declining incidence and cost effectiveness in the context of an elimination campaign; (ii) international aid and its effect on resource constraints; and (iii) supranational priority setting, all affect how health economists might use a cost-effectiveness threshold. Consensus and guidance on how to determine and interpret cost-effectiveness thresholds in the context of internationally financed elimination campaigns is greatly needed. (iv) Malaria interventions are often complimentary and evaluations may need to construct intervention bundles to represent relevant policy positions as sets of mutually exclusive alternatives. (v) Geographic targeting is a key aspect of malaria policy making that is only beginning to be addressed in economic evaluations. An approach to budget-based geographic resource allocation is described in an accompanying paper in this issue and addresses some of these methodological challenges.

Dynamic Transmission Economic Evaluation of Infectious Disease Interventions in Low- and Middle-Income Countries: A Systematic Literature Review.

Economic evaluation using dynamic transmission models is important for capturing the indirect effects of infectious disease interventions. We examine the use of these methods in low- and middle-income countries, where infectious diseases constitute a major burden. This review is comprised of two parts: (1) a summary of dynamic transmission economic evaluations across all disease areas published between 2011 and mid-2014 and (2) an in-depth review of mosquito-borne disease studies focusing on health economic methods and reporting. Studies were identified through a systematic search of the MEDLINE database and supplemented by reference list screening. Fifty-seven studies were eligible for inclusion in the all-disease review. The most common subject disease was HIV/AIDS, followed by malaria. A diverse range of modelling methods, outcome metrics and sensitivity analyses were used, indicating little standardisation. Seventeen studies were included in the mosquito-borne disease review. With notable exceptions, most studies did not employ economic evaluation methods beyond calculating a cost-effectiveness ratio or net benefit. Many did not adhere to health care economic evaluations reporting guidelines, particularly with respect to full model reporting and uncertainty analysis. We present a summary of the state-of-the-art and offer recommendations for improved implementation and reporting of health economic methods in this crossover discipline.

Using Economic Evidence to Set Healthcare Priorities in Low-Income and Lower-Middle-Income Countries: A Systematic Review of Methodological Frameworks.

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks--which incorporate economic evaluation evidence--for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence.

Malaria community health workers in Myanmar: a cost analysis.

BACKGROUND: Myanmar has the highest malaria incidence and attributed mortality in South East Asia with limited healthcare infrastructure to manage this burden. Establishing malaria Community Health Worker (CHW) programmes is one possible strategy to improve access to malaria diagnosis and treatment, particularly in remote areas. Despite considerable donor support for implementing CHW programmes in Myanmar, the cost implications are not well understood. METHODS: An ingredients based micro-costing approach was used to develop a model of the annual implementation cost of malaria CHWs in Myanmar. A cost model was constructed based on activity centres comprising of training, patient malaria services, monitoring and supervision, programme management, overheads and incentives. The model takes a provider perspective. Financial data on CHWs programmes were obtained from the 2013 financial reports of the Three Millennium Development Goal fund implementing partners that have been working on malaria control and elimination in Myanmar. Sensitivity and scenario analyses were undertaken to outline parameter uncertainty and explore changes to programme cost for key assumptions. RESULTS: The range of total annual costs for the support of one CHW was US$ 966-2486. The largest driver of CHW cost was monitoring and supervision (31-60% of annual CHW cost). Other important determinants of cost included programme management (15-28% of annual CHW cost) and patient services (6-12% of annual CHW cost). Within patient services, malaria rapid diagnostic tests are the major contributor to cost (64% of patient service costs). CONCLUSION: The annual cost of a malaria CHW in Myanmar varies considerably depending on the context and the design of the programme, in particular remoteness and the approach to monitoring and evaluation. The estimates provide information to policy makers and CHW programme planners in Myanmar as well as supporting economic evaluations of their cost-effectiveness.

Cost effectiveness and resource allocation of Plasmodium falciparum malaria control in Myanmar: a modelling analysis of bed nets and community health workers.

BACKGROUND: Funding for malaria control and elimination in Myanmar has increased markedly in recent years. While there are various malaria control tools currently available, two interventions receive the majority of malaria control funding in Myanmar: (1) insecticide-treated bed nets and (2) early diagnosis and treatment through malaria community health workers. This study aims to provide practical recommendations on how to maximize impact from investment in these interventions. METHODS: A simple decision tree is used to model intervention costs and effects in terms of years of life lost. The evaluation is from the perspective of the service provider and costs and effects are calculated in line with standard methodology. Sensitivity and scenario analysis are undertaken to identify key drivers of cost effectiveness. Standard cost effectiveness analysis is then extended via a spatially explicit resource allocation model. FINDINGS: Community health workers have the potential for high impact on malaria, particularly where there are few alternatives to access malaria treatment, but are relatively costly. Insecticide-treated bed nets are comparatively inexpensive and modestly effective in Myanmar, representing a low risk but modest return intervention. Unlike some healthcare interventions, bed nets and community health workers are not mutually exclusive nor are they necessarily at their most efficient when universally applied. Modelled resource allocation scenarios highlight that in this case there is no "one size fits all" cost effectiveness result. Health gains will be maximized by effective targeting of both interventions.

Buy now, saved later? The critical impact of time-to-pandemic uncertainty on pandemic cost-effectiveness analyses.

BACKGROUND: Investment in pandemic preparedness is a long-term gamble, with the return on investment coming at an unknown point in the future. Many countries have chosen to stockpile key resources, and the number of pandemic economic evaluations has risen sharply since 2009. We assess the importance of uncertainty in time-to-pandemic (and associated discounting) in pandemic economic evaluation, a factor frequently neglected in the literature to-date. METHODS: We use a probability tree model and Monte Carlo parameter sampling to consider the cost effectiveness of antiviral stockpiling in Cambodia under parameter uncertainty. Mean elasticity and mutual information (MI) are used to assess the importance of time-to-pandemic compared with other parameters. We also consider the sensitivity to choice of sampling distribution used to model time-to-pandemic uncertainty. RESULTS: Time-to-pandemic and discount rate are the primary drivers of sensitivity and uncertainty in pandemic cost effectiveness models. Base case cost effectiveness of antiviral stockpiling ranged between is US$112 and US$3599 per DALY averted using historical pandemic intervals for time-to-pandemic. The mean elasticities for time-to-pandemic and discount rate were greater than all other parameters. Similarly, the MI scores for time to pandemic and discount rate were greater than other parameters. Time-to-pandemic and discount rate were key drivers of uncertainty in cost-effectiveness results regardless of time-to-pandemic sampling distribution choice. CONCLUSIONS: Time-to-pandemic assumptions can "substantially" affect cost-effectiveness results and, in our model, is a greater contributor to uncertainty in cost-effectiveness results than any other parameter. We strongly recommend that cost-effectiveness models include probabilistic analysis of time-to-pandemic uncertainty.

Artemisinin resistance--modelling the potential human and economic costs.

BACKGROUND: Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. METHODS: This analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool. RESULTS: Using conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment. CONCLUSIONS: These 'ballpark' figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world.

Cost of treating inpatient falciparum malaria on the Thai-Myanmar border.

BACKGROUND: Despite demonstrated benefits and World Health Organization (WHO) endorsement, parenteral artesunate is the recommended treatment for patients with severe Plasmodium falciparum malaria in only one fifth of endemic countries. One possible reason for this slow uptake is that a treatment course of parenteral artesunate is costlier than quinine and might, therefore, pose a substantial economic burden to health care systems. This analysis presents a detailed account of the resources used in treating falciparum malaria by either parenteral artesunate or quinine in a hospital on the Thai-Myanmar border. METHODS: The analysis used data from four studies, with random allocation of inpatients with falciparum malaria to treatment with parenteral artesunate or quinine, conducted in Mae Sot Hospital, Thailand from 1995 to 2001. Detailed resource use data were collected during admission and unit costs from the 2008 hospital price list were applied to these. Total admission costs were broken down into five categories: 1) medication; 2) intravenous fluids; 3) disposables; 4) laboratory tests; and 5) services. RESULTS: While the medication costs were higher for patients treated with artesunate, total admission costs were similar in those treated with quinine, US$ 243 (95% CI: 167.5-349.7) and in those treated with artesunate US$ 190 (95% CI: 131.0-263.2) (P=0.375). For cases classified as severe malaria (59%), the total cost of admission was US$ 298 (95% CI: 203.6-438.7) in the quinine group as compared with US$ 284 (95% CI: 181.3-407) in the artesunate group (P=0.869). CONCLUSION: This analysis finds no evidence for a difference in total admission costs for malaria inpatients treated with artesunate as compared with quinine. Assuming this is generalizable to other settings, the higher cost of a course of artesunate should not be considered a barrier for its implementation in the treatment of malaria.

Ethics, economics, and the use of primaquine to reduce falciparum malaria transmission in asymptomatic populations.

Yoel Lubell and colleagues consider ethical and economic perspectives on mass drug administration of primaquine to limit transmission of P. falciparum malaria. Please see later in the article for the Editors' Summary.

Priority setting in global health: towards a minimum DALY value.

Rational and analytic healthcare decision making employed by many national healthcare-funding bodies could also be expected from global health donors. Cost effectiveness analysis of healthcare investment options presents the effectiveness of a particular action in proportion to the resources required, and cost effectiveness thresholds, while somewhat arbitrary, define the level at which the investment can be considered value for money. Currently, cost effectiveness thresholds reflect the national budget context or willingness-to-pay, which is problematic when making cross-country comparisons. Defining a global minimum monetary value for the disability adjusted life year (DALY) would in effect set a global baseline cost effectiveness threshold. A global minimum DALY value would reflect a universal minimum value on human health, irrespective of a national provider's willingness or ability to pay. A minimum DALY value and associated threshold has both limitations and flaws but is justified on similar grounds to the Millennium Development Goals or the absolute poverty threshold and has the potential to radically improve transparency and efficiency of priority setting in global health.

Distribution of selected healthcare resources for influenza pandemic response in Cambodia.

INTRODUCTION: Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. METHODS: A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. RESULTS: Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution across Cambodia. Distribution mapping at the local level can inform policy decisions on where to stockpile resources in advance of and for reallocation in the event of a pandemic. These findings will be useful in determining future health resource investment, both for pandemic preparedness and for general health system strengthening, and provide a foundation for future analyses of equity in health services provision for pandemic mitigation planning in Cambodia.

Human H5N1 influenza infections in Cambodia 2005-2011: case series and cost-of-illness.

BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia. METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness. RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0% comprised direct medical provider costs, including diagnostic testing (41.2%), pharmaceuticals (28.4%), hospitalisation (10.4%), oxygen (4.4%) and outpatient consultations (0.6%). Patient or family costs were US$45 per patient (15.0%) of total economic cost. CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness.