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Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to Gd(III). The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd(III) ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β-gal.

Objective? To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. Methods? Prospective observational study of drug dispensing practices at baseline and during the 3?years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1?month per quarter, documenting a total of 271?953 patient encounters in the three districts. Results? In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP?+?AS during the intervention period. Of patients who received SP?+?AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. Conclusions? The uptake of SP?+?AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.

An outbreak of apparent food-borne illness following a church gathering was promptly reported to the Maine Bureau of Health. Gastrointestinal symptoms among church attendees were initially attributed to consumption of leftover sandwiches that had been served the previous day. However, a rapid epidemiological and laboratory assessment revealed the etiology of illness, including the death of an elderly gentleman, was not food-borne in origin. A criminal investigation determined that deliberate arsenic contamination of the brewed coffee by one of the church members was the source of the outbreak. Public health officials and criminal investigators must be aware that intentional biologic aggression can initially present as typical unintentional disease outbreaks. Practitioners must also consider the need to properly maintain and preserve potential forensic evidence. This case demonstrates the key role public health practitioners may play in criminal investigations.

The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care-seekers obtaining appropriate treatment.Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels.

OBJECTIVE To measure the direct cost burdens (health care expenditure as a percent of total household expenditure) for households in rural South Africa, and examine the expenditure and use patterns driving those burdens, in a setting with free public primary health care and hospital exemptions for the poor. METHODS Data on illness events, treatment patterns and health expenditure in the previous month were assessed from a cross-sectional survey of 280 households conducted in the Agincourt Health and Demographic Surveillance site, South Africa. RESULTS On average, a household experiencing illness incurred a direct cost burden of 4.5% of total household expenditure. A visit to a public clinic generated a mean burden of 1.3%. Complex sequences of treatments led 20% of households to incur a burden over 10%, with transport costs generating 42% of this burden. An outpatient public hospital visit generated a burden of 8.2%, as only 58% of those eligible obtained an exemption; inpatient stays incurred a burden of 45%. Consultations with private providers incurred a mean burden of 9.5%. About 38% of individuals who reported illness did not take any treatment action, 55% of whom identified financial and perceived supply-side barriers as reasons. CONCLUSION The low overall mean cost burden of 4.5% suggests that free primary care and hospital exemptions provided financial protection. However, transport costs, the difficulty of obtaining hospital exemptions, use of private providers, and complex treatment patterns meant state-provided protection had limitations. The significant non-use of care shows the need for other measures such as more outreach services and more exemptions in rural areas. The findings also imply that fee removal anywhere must be accompanied by wider measures to ensure improved access.

This paper analyses household coping strategies for illness in four Lao villages. The villagers dealt with health expenditure themselves, using coping mechanisms which drew mainly on social networks within the community. They strongly believed in the principle of paying user fees and did not consider exemption from fees an option. A total of 12 households (6 per cent of households) faced catastrophic expenditure arising from healthcare payments. The national policy on exemptions did not protect the poor and the study demonstrates that there is an urgent need for the government to improve the design and implementation of exemptions or reform the policy on subsidising health care. Copyright © 2009 John Wiley & Sons, Ltd.

Illness is a major risk to people's livelihoods in resource-poor settings, particularly where there are rising levels of chronic illness. Measures that improve access to treatment are increasingly seen as a vital form of social protection for vulnerable households, and central to the achievement of the Millennium Development Goals. International attention is also focussed on cash transfers as a strand of social protection, and on the potential complementarities between free health care and cash transfers in assisting vulnerable people to cope with illness-related shocks. South Africa provides an interesting setting to examine how households are accessing social protection measures because the government has removed some user fees, implemented hospital-level exemptions and extended cash transfers including the non-contributory pension and child support grant. This paper presents findings from household research in rural South Africa. Qualitative and quantitative methods were used to assess the links between illness-related costs and impoverishment over time, the protection effects of free health services, cash transfers and social networks, and the factors influencing access to these three forms of social protection. Different degrees of success in drawing on these resources affected capacity to cope with illnesses and made a considerable difference to whether households sustained their livelihoods, struggled or declined. Cash transfers combined well with free health care to build resilience among some households. However, households without access to at least two strands of the social protection net were impoverished by the direct and indirect costs of long-term illnesses. The implications for policies on improving the uptake and coverage of social protection measures are discussed. Copyright © 2009 John Wiley & Sons, Ltd.

When the Thai universal coverage (UC) scheme was established, the government decided to exclude renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients from the benefit package, though RRT was included in two other public health insurance schemes. Access to RRT for UC members thus depended on the ability to pay. This study assessed the economic impact of RRT costs on Thai households of different economic status focusing on three issues: (1) the use of RRT; (2) the financial burden of health care payments and (3) household strategies for coping with RRT costs. In-depth case studies of 20 households covered by the UC scheme and having ESRD patients were undertaken using three qualitative data collection approaches: semi-structured and in-depth interviews, and direct observation. Poorer and richer households in urban and rural areas of Nakorn Ratchasima province, a large province in the Northeast where more than 20 per cent of households live below the national poverty line, were purposively selected. The study was conducted in early 2005 and households were visited every 2 weeks for 3 months. Interviews were transcribed and analysed using a thematic approach. The decision to exclude RRT from the UC benefit package created financial barriers to RRT and had a substantial economic impact on poorer ESRD patients. Inadequate dialyses and erythropoietin injections to correct anaemia appeared to be a major cause of death for poorer patients. Household expenditure on RRT took 25–68 per cent of total income or 31–52 per cent of total expenditure, which meant all poorer patients faced catastrophic health spending. In contrast, richer patients had adequate dialyses, resulting in a higher survival rate and quality of life than poorer counterparts. Various coping strategies were employed by poorer patients; these included reducing frequency of dialyses, reducing food consumption, using public transportation to hospitals and taking high interest loans. The RRT cost burden not only impacted patients but also their household members and relatives who provided financial support. Given the two UC policy objectives of equitable access to health care and financial risk protection, the catastrophic impact of RRT costs on poorer households questions the appropriateness of excluding RRT from the UC benefit package. This issue requires further serious attention by the Thai government. Copyright © 2009 John Wiley & Sons, Ltd.

OBJECTIVE To explore the cost-effectiveness of artesunate against quinine based principally on the findings of a large multi-centre trial carried out in Southeast Asia. METHODS Trial data were used to compare mortality of patients with severe malaria, treated with either artesunate or quinine. This was combined with retrospectively collected cost data to estimate the incremental cost per death averted with the use of artesunate instead of quinine. RESULTS The incremental cost per death averted using artesunate was approximately 140 USD. Artesunate maintained this high level of cost-effectiveness also when allowing for the uncertainty surrounding the cost and effectiveness assessments. CONCLUSION This analysis confirms the vast superiority of artesunate for treatment of severe malaria from an economic as well as a clinical perspective.

A common challenge faced by voluntary community based insurance (CBI) schemes is ensuring re-enrolment of their members. This study examines factors that may explain dropout from a CBI scheme targeting poorer self-employed women in Gujarat. Members who exited from the scheme were poorer and less educated; had weaker links with the promoting institution; and used the scheme less in the preceding year. The primary reason for dropping out was that members were not contacted by programme staff to re-enrol. Scheme administrators can reduce dropout rates by maintaining better contact with scheme members and systematically seeking them out at the time of enrolment. Such relatively simple improvements in scheme administration can enhance the efficiency and equity of the scheme. Copyright © 2006 John Wiley & Sons, Ltd.

OBJECTIVE: To document the cost incurred by the Tanzanian government by changing the policy on first-line treatment of malaria, from chloroquine to sulfadoxine-pyrimethamine. METHODS: Costs were analysed from the perspective of the Ministry of Health and included all sources of funding. Costs external to the public health sector (e.g. private and community costs) were not included. The base case analysis adopted an incremental rather than a full cost approach, assuming that an organizational infrastructure was already in place. However, specific attention was paid to the burden placed on National Malaria Control Program staff. We also costed activities planned but not implemented to estimate the total expense for an 'ideal' process. RESULTS: Total costs were Tsh 795 million (USD 813,743), with the largest proportion accounted for by training. Costs of the policy change process were equivalent to about 4% of annual government and donor expenditure on malaria and to about 1% of overall public expenditure on health. A number of planned activities were not implemented; including these would bring the total cost to Ts 880 million (USD 896,130). CONCLUSION: On top of extra costs for the drugs themselves, a change in treatment policy requires time, resources and substantial management capacity at national and local level. A better understanding of these issues and the costs involved benefits countries planning and implementing policy change.

This article examines the existence of price discrimination for obstetric services in two private hospitals in Bangladesh, and considers the welfare consequences of such discrimination, i.e. whether or not price discrimination benefited the poorer users. Data on 1212 normal and caesarean section patients discharged from the two hospitals were obtained. Obstetric services were chosen because they are relatively standardised and the patient population is relatively homogeneous, so minimising the scope and scale of product differentiation due to procedure and case-mix differences. The differences between the hospital list price for delivery and actual prices paid by patients were calculated to determine the average rate of discount. The welfare consequences of price discrimination were assessed by testing the differences in mean prices paid by patients from three income groups: low, middle and high. The results suggest that two different forms of price discrimination for obstetric services occurred in both these hospitals. First, there was price discrimination according to income, with the poorer users benefiting from a higher discount rate than richer ones; and second, there was price discrimination according to social status, with three high status occupational groups (doctors, senior government officials, and large businessmen) having the highest probability of receiving some level of discount.

OBJECTIVES To characterize availability of fever and malaria medicines within the retail sector in rural Tanzania, assess the likely public health implications, and identify opportunities for policy interventions to increase the coverage of effective treatment. METHODS A census of retailers selling drugs was undertaken in the areas under demographic surveillance in four Tanzanian districts, using a structured questionnaire. RESULTS Drugs were stocked by two types of retailer: a large number of general retailers (n = 675) and a relatively small number of drug shops (n = 43). Almost all outlets stocked antipyretics/painkillers. One-third of general retailers stocking drugs had antimalarials, usually chloroquine alone. Almost all drug shops stocked antimalarials (98%): nearly all had chloroquine, 42% stocked quinine, 37% sulphadoxine-pyrimethamine and 30% amodiaquine. A large number of antimalarial brands were available. Population ratios indicate the relative accessibility of retail drug providers compared with health facilities. Drug shop staff generally travelled long distances to buy from drugs wholesalers or pharmacies. General retailers bought mainly from local general wholesalers, with a few general wholesalers accounting for a high proportion of all sources cited. CONCLUSIONS Drugs were widely available from a large number of retail outlets. Potential negative implications include provision of ineffective drugs, confusion over brand names, uncontrolled use of antimalarials, and the availability of components of potential combination therapy regimens as monotherapies. On the other hand, this active and highly accessible retail market provides opportunities for improving the coverage of effective antimalarial treatment. Interventions targeted at all drug retailers are likely to be costly to deliver and difficult to sustain, but two promising points for targeted intervention are drug shops and selected general wholesalers. Retail quality may also be improved through consumer education, and modification of the chemical quality, packaging and price of products entering the retail distribution chain.

Summary • The purpose of the study was to identify the current and perceived clinical role functions of advanced nurse practitioners (ANPs) within the complementary health paradigm and their learning needs. • Participants were asked to identify their referral practices to complementary practitioners, current and perceived clinical activities with respect to six most popular complementary therapies, learning needs and concerns regarding their use. • A random sample of 389 ANPs registered with the College of Nurses of Ontario participated in a mailed survey using a modified Dillman approach, an established method for improving response rate through repeated mailings. • An overall response rate of 55.3% (215 out of 389 eligible participants) was achieved. • The results show that ANPs are currently engaged in clinical activities involving these therapies, with a trend towards more participation in assessing the need for them and counselling on the risks and benefits. • ANPs are interested in validating the use of these therapies and acquiring more knowledge on the scientific principles, evidence of efficacy, pharmacology and potential interactions with conventional medicine.

A key issue in the expansion of access to priority health services is how best to implement scaling up efforts. In this paper, we explore the relative merits of vertical and horizontal delivery modes; review the literature on the impact of vertical programmes on health systems and on experiences of integrating these programmes; and analyse health interventions in terms of their different modes of delivery within the health system infrastructure. We conclude that expanding access to priority health services requires the concerted use of both modes of delivery, according to the capacity of health systems as it changes over time. © 2003 John Wiley and Sons, Ltd.

This paper reviews the current evidence base regarding efforts to overcome constraints to effective health service delivery in low and middle-income countries. A systematic literature review was chosen as the approach to gather and analyse existing knowledge about how to improve the ‘close-to-client’ health system. We focused on three levels of constraints: community and household, the health services delivery level itself, and health sector policy and strategic management. In total, 116 studies were reviewed and their main findings presented. The results should be interpreted with caution due to the considerable limitations in the existing evidence base. Copyright © 2003 John Wiley & Sons, Ltd.

This paper adopts three approaches to classifying countries by level of constraint, in order to inform the choice of strategies for expanding access to health interventions in different contexts. We find substantial heterogeneity across the 84 low-income and (all) sub-Saharan African countries analysed. Poor sub-Saharan African countries are the most highly constrained; Asian countries, in general, less constrained; and the two Asian giants, China and India, consistently fall above the median. Former Soviet Union countries rank low in terms of governance, but high for health systems variables. Only 10 per cent of the total population of the countries included lives in countries with the greatest constraints. The potential applications of the analysis are discussed, as are the limitations of the cross-sectional, macro level approach. © 2003 John Wiley and Sons, Ltd.

The Commission on Macroeconomics and Health recommended a significant expansion in funding for health interventions in poor countries. However, there are a range of constraints to expanding access to health services: as well as an absolute lack of resources, access to health interventions is hindered by problems of demand, weak service delivery systems, policies at the health and cross-sectoral levels, and constraints related to governance, corruption and geography. This special issue is devoted to analysis of the nature and intensity of these constraints, and how they can best be overcome

Access to effective treatment would substantially reduce the burden of malaria in sub-Saharan Africa, but resistance to chloroquine, the most commonly used first line drug, is now widespread. There has been considerable debate over the level of chloroquine resistance at which a new first line drug should be adopted. Two issues make this an extremely complex decision: it involves trade-offs in costs and health outcomes over time; and many of the parameters are uncertain. A modelling approach was identified as appropriate for addressing these issues. The costs and effects of changing from chloroquine to sulphadoxine-pyrimethamine (SP) as the first line drug were modelled over 10 years, allowing for growth in drug resistance. Probabilistic sensitivity analysis was used to allow for the high levels of parameter uncertainty. The optimal year of switch was highly dependent on both empirical values, such as initial resistance and resistance growth rates, and on subjective values, such as the time preferences of policy-makers. It was not possible to provide policy-makers with a definitive threshold resistance level at which to switch, but the model can be used as an analytical tool to structure the problem, explore trade-offs, and identify areas for which data are lacking.

This paper draws on data from Sierra Leone and secondary data from elsewhere to show that the rural poor can be disproportionately disadvantaged by user charges for health care paying a higher percentage of their incomes for health care than wealthier households. Cost sharing systems at primary care level should include exemptions for the poor but rarely succeed in consistently protecting them. The regressivity of health expenditures also results from lack of protection from the higher costs of less-frequently used expensive providers. In Sierra Leone the burden of curative treatment costs for all groups came mainly from private and nongovernmental organization providers. Proximity to facilities appeared a more important factor in their use than average prime levels. Even if a perfect exemption system existed at government primary care facilities it would not have had much overall effect because of their relatively small contribution to household health expenditures. The financial burden on households could be relieved by making basic health facilities more accessible and at hospital level using additional resources generated through improved efficiency and cross-subsidization to provide exemptions. Also pricing policy should take into account local economic conditions. Insurance/prepayment schemes covering the cost of hospitalization would come closer to an ideal solution but have been implemented in very few of the poorer countries. (authors)

New public management (NPM) ideas have been reflected in the international health sector reform agenda. This paper summarizes the extent and depth of reform in the five countries studied, as reflected in four key policy arrangements, and reviews the various dimensions of capacity which have hindered policy development and implementation. The paper concludes that NPM reforms place demands on government which are not only technically complex but require political leadership, major institutional reform and shifts in organizational culture: it was thus not surprising that none of the case-study countries had undertaken far-reaching NPM reforms in the health sector. Key lessons for capacity strengthening are drawn from the country experiences. Copyright © 1999 John Wiley & Sons, Ltd.

Using case-study material of contracting for clinical and ancillary services in the health care sector of developing countries this article examines the capacities required for successful contracting and the main constraints which developing country governments face in developing and implementing contractual arrangements. Required capacities differ according to the type of service being contracted and the nature of the contractor. Contracting for clinical as opposed to ancillary services poses considerably greater challenges in terms of the information required for monitoring and contract design. Yet in some of the case-studies examined problems arose owing to governments limited capacity to perform even very basic functions such as paying contractors in a timely manner and keeping records of contracts negotiated. The external environment within which contracting takes place is also critical; in particular the case-studies indicate that contracts embedded in slow-moving rule-ridden bureaucracies will face substantial constraints to successful implementation. The article suggests that governments need to assess required capacities on a service-by-service basis. For any successful contracting basic administrative systems must be functioning. In addition there should be development of guidelines for contracting clear lines of communication between all agents involved in the contracting process and regular evaluations of contractual arrangements. Finally in cases where government has weak capacity direct service provision may be a lower- risk delivery strategy. (authors)

A world-wide revolution in thinking about public sector management has occurred in recent years, termed the ‘new public management’. It aims to improve the efficiency of service provision primarily through the introduction of market mechanisms into the public sector. The earliest form of marketization in developed countries has tended to be the introduction of competitive tendering and contracts for the provision of public services. In less wealthy countries, the language of contracting is heard with increasing frequency in discussions of health sector reform despite the lack of evidence of the virtues (or vices) of contracting in specific country settings. This paper examines the economic arguments for contracting district hospital care in two rather different settings in Southern Africa: in South Africa using private-for-profit providers, and in Zimbabwe using NGO (mission) providers. The South African study compared the performance of three ‘contractor’ hospitals with three government-run hospitals, analysing data on costs and quality. There were no significant differences in quality between the two sets of hospitals, but contractor hospitals provided care at significantly lower unit costs. However, the cost to the government of contracting was close to that of direct provision, indicating that the efficiency gains were captured almost entirely by the contractor. A crucial lesson from the study is the importance of developing government capacity to design and negotiate contracts that ensure the government is able to derive significant efficiency gains from contractual arrangements. In other parts of Africa, contracts for hospital care are more likely to be agreed with not-for-profit providers. The Zimbabwean study compared the performance of two government district hospitals with two district ‘designated’ mission hospitals. It found that the two mission hospitals delivered similar services to those of the two government hospitals but at substantially lower unit cost. The nature of the contract between government and missions was implicit rather than explicit and of long standing. On the whole the mission organizations felt the informal nature of the agreement was advantageous, though the government plans to introduce service contracts at district level with all hospitals, both government and mission. The paper concludes by identifying concerns raised by the case-studies that are of relevance to other countries considering the introduction of explicit contractual arrangements for district hospital provision.

This article reviews alternative decentralization policies for the health sector. It discusses the forms that decentralization can take, illustrating these with country examples. It then considers the choice of levels in a decentralization policy and the desirability of the creation of health boards or authorities. Decentralized authorities can be given differing levels of responsibility for different tasks: those considered here are revenue raising, policy-making and planning, resource allocation, funding of service provision and interagency and intersec-toral coordination. The article concludes by considering some criteria for evaluating decentralization approaches.

Summary objective To investigate the variation in malaria parasitaemia, reported fever, care seeking, antimalarials obtained and household expenditure by socio-economic status (SES), and to assess the implications for ensuring equitable and appropriate use of antimalarial combination therapy. methods A total of 2500 households were surveyed in three rural districts in southern Tanzania in mid-2001. Blood samples and data on SES were collected from all households. Half the households completed a detailed questionnaire on care seeking and treatment costs. Households were categorised into SES thirds based on an index of household wealth derived using principal components analysis. results Of individuals completing the detailed survey, 16% reported a fever episode in the previous 2 weeks. People from the better-off stratum were significantly less likely to be parasitaemic, and significantly more likely to obtain antimalarials than those in the middle or poor stratum. The better treatment obtained by the better off led them to spend two to three times more than the middle and poor third spent. This reflected greater use of non-governmental organisation (NGO) facilities, which were the most expensive source of care, and higher expenditure at NGO facilities and drug stores. conclusion The coverage of appropriate malaria treatment was low in all SES groups, but the two poorer groups were particularly disadvantaged. As countries switch to antimalarial combination therapy, distribution must be targeted to ensure that the poorest groups fully benefit from these new and highly effective medicines.