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Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia
Shunmay Yeung, Edith Patouillard, Henrietta Allen, Duong Socheat
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-243
Abstract: In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme.The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas.The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers
Spread of anti-malarial drug resistance: Mathematical model with implications for ACT drug policies
Wirichada Pongtavornpinyo, Shunmay Yeung, Ian M Hastings, Arjen M Dondorp, Nicholas PJ Day, Nicholas J White
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-229
Abstract: A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment.The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with mismatched half-lives, together with reducing malaria transmission through vector control measures.This paper has demonstrated the use of a comprehensive mathematical model to describe malaria transmission and the spread of drug resistance. The model is strongly linked to the empirical evidence obtained from extensive data available from various sources. This model can be a useful tool to inform the design of treatment policies, particularly at a time when ACT has been endorsed by WHO as first-line treatment for falciparum malaria worldwide.For the past half-century, the malaria parasites of humans
Cost of increasing access to artemisinin combination therapy: the Cambodian experience
Shunmay Yeung, Wim Van Damme, Duong Socheat, Nicholas J White, Anne Mills
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-84
Abstract: This paper presents an incremental cost analysis of some of these interventions in Cambodia, the first country to change national antimalarial drug policy to an ACT of artesunate and mefloquine. These costs include the cost of rapid diagnostic tests (RDTs), the cost of blister-packaging the drugs locally and the costs of increasing access to diagnosis and treatment to remote communities through malaria outreach teams (MOTs) and Village Malaria Workers (VMW).At optimum productive capacity, the cost of blister-packaging cost under $0.20 per package but in reality was significantly more than this because of the low rate of production. The annual fixed cost (exclusive of RDTs and drugs) per capita of the MOT and VMW schemes was $0.44 and $0.69 respectively. However because the VMW scheme achieved a higher rate of coverage than the MOT scheme, the cost per patient treated was substantially lower at $5.14 compared to $12.74 per falciparum malaria patient treated. The annual cost inclusive of the RDTs and drugs was $19.31 for the MOT scheme and $11.28 for the VMW scheme given similar RDT positivity rates of around 22% and good provider compliance to test results.In addition to the cost of ACTs themselves, substantial additional investments are required in order to ensure that they reach the targeted population via appropriate delivery systems and to ensure that they are used appropriately. In addition, differences in local conditions, in particular the prevalence of malaria and the pre-existing infrastructure, need to be considered in choosing appropriate diagnostic and delivery strategies.Artemisinin combination therapies (ACTs) are now the officially recommended treatment for Plasmodium falciparum malaria in most malaria-endemic countries [1-3]. However, there are significant challenges in the actual implementation of this change in antimalarial drug policy. In the era of cheap monotherapies, namely chloroquine and sulphadoxine-pyrimethamine (SP), treatment for malaria w
Access to artemisinin combination therapy for malaria in remote areas of Cambodia
Shunmay Yeung, Wim Van Damme, Doung Socheat, Nicholas J White, Anne Mills
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-96
Abstract: A cross-sectional survey was carried out in three different types of intervention area: with VMWs, MOTs and no specific interventions. Individuals with a history of fever in the last three weeks were included in the study and completed a questionnaire on their treatment seeking and drug usage behaviour. Blood was taken for a rapid diagnostic test (RDT) and data on the household socio-economic status were also obtained.In areas without specific interventions, only 17% (42/251) of respondents received a biological diagnosis, 8% (17/206) of respondents who received modern drug did so from a public health facility, and only 8% of them (17/210) received A+M. Worryingly, 78% (102/131) of all artemisinin use in these areas was as a monotherapy. However, both the VMW scheme and MOT scheme significantly increased the likelihood of being seen by a trained provider (Adjusted Odds Ratios (AOR) of 148 and 4 respectively) and of receiving A+M (AORs of 2.7 and 7.7 respectively).The coverage rates of appropriate diagnosis and treatment of malaria were disappointingly low and the use of artemisinin monotherapy alarmingly high. This reflects the fragmented nature of Cambodia's health system in remote areas and the reliance placed by these communities on informal vendors from whom artemisinin monotherapies are widely available. However VMWs in particular are an effective means of improving access to malaria diagnosis and treatment. The VMW scheme and the social marketing of RDTS and blister-packaged artesunate and mefloquine have both been scaled up nationally. Case management in the public sector has also reportedly improved. Given recent concerns regarding the development of artemisinin drug resistance on the Thai-Cambodia border, the effectiveness of these measures in reducing the use of artemisinin monotherapy needs to be urgently re-evaluated.Artemisinin combination therapies (ACTs) are now the official drug of choice in most malaria-endemic countries. Funds are being raised for
Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys
Megan Littrell, Hellen Gatakaa, Sochea Phok, Henrietta Allen, Shunmay Yeung, Char Chuor, Lek Dysoley, Duong Socheat, Angus Spiers, Chris White, Tanya Shewchuk, Desmond Chavasse, Kathryn A O'Connell
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-328
Abstract: Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined.Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors.While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of d
The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia
Richard J Maude, Wirichada Pontavornpinyo, Sompob Saralamba, Ricardo Aguas, Shunmay Yeung, Arjen M Dondorp, Nicholas PJ Day, Nicholas J White, Lisa J White
Malaria Journal , 2009, DOI: 10.1186/1475-2875-8-31
Abstract: A population dynamic mathematical modeling framework was developed to explore the relative effectiveness of a variety of containment interventions in eliminating artemisinin-resistant malaria in western Cambodia.The most effective intervention to eliminate artemisinin-resistant malaria was a switch of treatment from artemisinin monotherapy to ACT (mean time to elimination 3.42 years (95% CI 3.32–3.60 years). However, with this approach it is predicted that elimination of artemisinin-resistant malaria using ACT can be achieved only by elimination of all malaria. This is because the various forms of ACT are more effective against infections with artemisinin-sensitive parasites, leaving the more resistant infections as an increasing proportion of the dwindling parasite population.Containment of artemisinin-resistant malaria can be achieved by elimination of malaria from western Cambodia using ACT. The "last man standing" is the most resistant and thus this strategy must be sustained until elimination is truly achieved.The Thai-Cambodian border area is historically the source of the global diaspora of anti-malarial drug resistance. Resistance to chloroquine and sulphadoxine-pyrimethamine in Plasmodium falciparum originated there, spread across Asia and Africa, and caused millions of deaths [1]. The increase in malaria mortality is now being reversed where effective vector control measures and anti-malarials, principally artemisinin-based combination therapy (ACT), are being deployed [2]. Current initiatives to eliminate malaria are critically dependent on their continued efficacy.In the 2006, WHO Guidelines for the Treatment of Malaria [3] ACT became the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria in all endemic areas. Intravenous artesunate became the treatment of choice for severe malaria, except for children in Africa (where studies are in progress) [3,4]. These recommendations for the large-scale use of artemisinin derivatives we
Ethics, Economics, and the Use of Primaquine to Reduce Falciparum Malaria Transmission in Asymptomatic Populations
Yoel Lubell ,Lisa White,Sheila Varadan,Tom Drake,Shunmay Yeung,Phaik Yeong Cheah,Richard J. Maude,Arjen Dondorp,Nicholas P. J. Day,Nicholas J. White,Michael Parker
PLOS Medicine , 2014, DOI: 10.1371/journal.pmed.1001704
Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance
Richard J. Maude, Duong Socheat, Chea Nguon, Preap Saroth, Prak Dara, Guoqiao Li, Jianping Song, Shunmay Yeung, Arjen M. Dondorp, Nicholas P. Day, Nicholas J. White, Lisa J. White
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037166
Abstract: Background Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. Method and Findings A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. Conclusions The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.
Malaria morbidity in Papua Indonesia, an area with multidrug resistant Plasmodium vivax and Plasmodium falciparum
Muhammad Karyana, Lenny Burdarm, Shunmay Yeung, Enny Kenangalem, Noah Wariker, Rilia Maristela, Ketut Gde Umana, Ram Vemuri, Maurits J Okoseray, Pasi M Penttinen, Peter Ebsworth, Paulus Sugiarto, Nicholas M Anstey, Emiliana Tjitra, Richard N Price
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-148
Abstract: All laboratory-confirmed episodes of malaria in Timika, Papua, Indonesia, presenting to community primary care clinics and an inpatient facility were reviewed over a two-year period. In addition information was gathered from a house-to-house survey to quantify the prevalence of malaria and treatment-seeking behaviour of people with fever.Between January 2004 and December 2005, 99,158 laboratory-confirmed episodes of malaria were reported, of which 58% (57,938) were attributable to P. falciparum and 37% (36,471) to P. vivax. Malaria was most likely to be attributable to pure P. vivax in children under one year of age (55% 2,684/4,889). In the household survey, the prevalence of asexual parasitaemia was 7.5% (290/3,890) for P. falciparum and 6.4% (248/3,890) for P. vivax. The prevalence of P. falciparum infection peaked in young adults aged 15–25 years (9.8% 69/707), compared to P. vivax infection which peaked in children aged 1 to 4 years (9.5% 61/642). Overall 35% (1,813/5,255) of people questioned reported a febrile episode in the preceding month. Of the 60% of people who were estimated to have had malaria, only 39% would have been detected by the surveillance network. The overall incidence of malaria was therefore estimated as 876 per 1,000 per year (Range: 711–906).In this region of multidrug-resistant P. vivax and P. falciparum, both species are associated with substantial morbidity, but with significant differences in the age-related risk of infection.The true burden of malaria outside of sub-Saharan Africa has been underestimated [1], largely due to the lack of accurate estimates from India and Indonesia, whose combined population accounts for 20% of the world's population. In Indonesia, almost half of the country's population of 250 million live in malaria-endemic areas. In Java and Bali, where approximately 70% of the country's population live, malaria is hypoendemic and vivax malaria predominates. In the outer island groups, the incidence of malaria is much
Cost-effectiveness of parenteral artesunate for treating children with severe malaria in sub-Saharan Africa
Lubell,Yoel; Riewpaiboon,Arthorn; Dondorp,Arjen M; Seidlein,Lorenz von; Mokuolu,Olugbenga A; Nansumba,Margaret; Gesase,Samwel; Kent,Alison; Mtove,George; Olaosebikan,Rasaq; Ngum,Wirichada Pan; Fanello,Caterina I; Hendriksen,Ilse; Day,Nicholas PJ; White,Nicholas J; Yeung,Shunmay;
Bulletin of the World Health Organization , 2011, DOI: 10.2471/BLT.11.085878
Abstract: objective: to explore the cost-effectiveness of parenteral artesunate for the treatment of severe malaria in children and its potential impact on hospital budgets. methods: the costs of inpatient care of children with severe malaria were assessed in four of the 11 sites included in the african quinine artesunate malaria treatment trial, conducted with over 5400 children. the drugs, laboratory tests and intravenous fluids provided to 2300 patients from admission to discharge were recorded, as was the length of inpatient stay, to calculate the cost of inpatient care. the data were matched with pooled clinical outcomes and entered into a decision model to calculate the cost per disability-adjusted life year (daly) averted and the cost per death averted. findings: the mean cost of treating severe malaria patients was similar in the two study groups: 63.5 united states dollars (us$) (95% confidence interval, ci: 61.7-65.2) in the quinine arm and us$ 66.5 (95% ci: 63.7-69.2) in the artesunate arm. children treated with artesunate had 22.5% lower mortality than those treated with quinine and the same rate of neurological sequelae: (artesunate arm: 2.3 dalys per patient; quinine arm: 3.0 dalys per patient). compared with quinine as a baseline, artesunate showed an incremental cost per daly averted and an incremental cost per death averted of us$ 3.8 and us$ 123, respectively. conclusion: artesunate is a highly cost-effective and affordable alternative to quinine for treating children with severe malaria. the budgetary implications of adopting artesunate for routine use in hospital-based care are negligible.
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