Search

Universal provision of iron supplements or iron-containing multiple micronutrient powders (MNPs) is widely used to prevent anemia in young children in low- and middle-income countries. The BRISC (Benefits and Risks of Iron Interventions in Children) trial compared iron supplements and MNPs with placebo in children2 y old in rural Bangladesh.We aimed to assess the cost-effectiveness of iron supplements or iron-containing MNPs among young children in rural Bangladesh.We did a cost-effectiveness analysis of MNPs and iron supplements using the BRISC trial outcomes and resource use data, and programmatic data from the literature. Health care costs were assessed from a health system perspective. We calculated incremental cost-effectiveness ratios (ICERs) in terms of US$ per disability-adjusted life-year (DALY) averted. To explore uncertainty, we constructed cost-effectiveness acceptability curves using bootstrapped data over a range of cost-effectiveness thresholds. One- and 2-way sensitivity analyses tested the impact of varying key parameter values on our results.Provision of MNPs was estimated to avert 0.0031 (95% CI: 0.0022, 0.0041) DALYs/child, whereas iron supplements averted 0.0039 (95% CI: 0.0030, 0.0048) DALYs/child, over 1 y compared with no intervention. Incremental mean costs were $0.75 (95% CI: 0.73, 0.77) for MNPs compared with no intervention and $0.64 ($0.62, $0.67) for iron supplements compared with no intervention. Iron supplementation dominated MNPs because it was cheaper and averted more DALYs. Iron supplementation had an ICER of $1645 ($1333, $2153) per DALY averted compared with no intervention, and had a 0% probability of being the optimal strategy at cost-effectiveness thresholds of $200 (reflecting health opportunity costs in Bangladesh) and $985 [half of gross domestic product (GDP) per capita] per DALY averted. Scenario and sensitivity analyses supported the base case findings.These findings do not support universal iron supplementation or micronutrient powders as a cost-effective intervention for young children in rural Bangladesh.This trial was registered at anzctr.org.au as ACTRN1261700066038 and trialsearch.who.int as U1111-1196-1125.

Background: Antiretroviral therapy (ART) for HIV has significantly reduced morbidity and mortality, but the drugs can be expensive. This study aims to estimate the lifetime cost of HIV management from the Australian healthcare perspective. Methods: A Markov cohort model, consisting of 21 health states based on CD4 count and line of ART, simulated disease progression over the lifetime of persons living with HIV. We reported costs using 2019 Australian dollars (A$) at a discount rate of 3·5% per annum. One-way sensitivity analysis was used to assess the impact of model inputs, and probabilistic sensitivity analyses were conducted to calculate the 95% confidence intervals for the lifetime cost estimate. Findings: The average discounted lifetime cost of HIV management was A$282,093 [95% CI: $194,206 – 421,345]. The largest proportion of lifetime cost was due to ART (92%). The lifetime cost was most sensitive to third- and second-line ART costs, followed by the probability of failing third-line therapy for those with CD4 count

The comparative clinical utility of the components of the psychological flexibility model of acceptance and commitment therapy (ACT) have not been equally evaluated. This study therefore conducted a feasibility and pilot two-arm dismantling trial by quarantining the self-as-context component. Sixteen participants were randomised to either 8 sessions of protocol-based ACT (Full-ACT) or 8 sessions of protocol-based ACT minus self-as-context (ACT-SAC). Process measures (flexibility and decentring) were taken at start of treatment, end of treatment, and at 6-week follow-up. Clinical outcome measures (functioning, anxiety, and depression) were collected on a session-by-session basis. Randomisation was well tolerated, all measures were completed, both interventions were competently delivered, and one adverse effect occurred in the full-ACT arm. Ten participants attended all 8 sessions creating a dropout rate of 37.50%. Clinical change appeared linear in both treatments and that treatment gains were maintained. Findings suggest that a full trial is possible and sample size calculations and methodological improvements are provided for this.

BackgroundScabies is a parasitic infestation with high global burden. Mass drug administrations (MDAs) are recommended for communities with a scabies prevalence of >10%. Quantitative analyses are needed to demonstrate the likely effectiveness of MDA recommendations. In this study, we compare the effectiveness of differing MDA strategies, supported by improved treatment access, on scabies prevalence in Monrovia, Liberia.MethodsWe developed an agent-based model of scabies transmission calibrated to demographic and epidemiological data from Monrovia. We used this model to compare the effectiveness of MDA scenarios for achieving scabies elimination and reducing scabies burden, as measured by time until recrudescence following delivery of an MDA and disability-adjusted-life-years (DALYs) averted. We also investigated the additional impact of improving access to scabies treatment following delivery of an MDA.ResultsOur model showed that 3 rounds of MDA delivered at 6-month intervals and reaching 80% of the population could reduce prevalence below 2% for 3 years following the final round, before recrudescence. When MDAs were followed by increased treatment uptake, prevalence was maintained below 2% indefinitely. Increasing the number of and coverage of MDA rounds increased the probability of achieving elimination and the DALYs averted.ConclusionsOur results suggest that acute reduction of scabies prevalence by MDA can support a transition to improved treatment access. This study demonstrates how modelling can be used to estimate the expected impact of MDAs by projecting future epidemiological dynamics and health gains under alternative scenarios.SummaryWe use an agent-based model to demonstrate that mass drug administration (MDA) programs can achieve sustained reduction in scabies prevalence. However, effective MDAs must be accompanied by systemic changes that increase the rate of scabies treatment to prevent recrudescence.

Background. Reducing the risk of recurrent P. vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment. Methods. This is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire. Results. Trial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and P. falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) of survey respondents acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1-2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p < 0.001. Conclusion. Adherence to malaria treatment was a socio-culturally embedded process during which patients (re-)evaluated the characteristics of the medicines in relation to the course of the illness, their past experiences with illness, and the perceived benefits of the treatment. Socio-cultural logics and practical challenges that underlie adherence are crucial to consider in the development and rollout of effective malaria treatment policies.

Tafenoquine has been licensed for the single-dose radical cure of Plasmodium vivax in adults; however, it is only recommended in patients with > 70% of normal glucose-6-phosphate dehydrogenase (G6PD) activity. Because this may hinder widespread use, we investigated sex-based treatment strategies in which all adult patients are tested with a qualitative G6PD rapid diagnostic test (RDT). Glucose-6-phosphate dehydrogenase normal males are prescribed tafenoquine in all three strategies, whereas G6PD normal females are prescribed either a low-dose 14-day primaquine regimen (PQ14, total dose 3.5 mg/kg) or a high-dose 7-day primaquine regimen (PQ7, total dose 7 mg/kg), or referred to a healthcare facility for quantitative G6PD testing before prescribing tafenoquine. Patients testing G6PD deficient are prescribed a weekly course of primaquine for 8 weeks. We compared the cost-effectiveness of these three strategies to usual care in four countries using a decision tree model. Usual care in Ethiopia does not include radical cure, whereas Afghanistan, Indonesia, and Vietnam prescribe PQ14 without G6PD screening. The cost per disability-adjusted life-year (DALY) averted was expressed through incremental cost-effectiveness ratios (ICERs). Compared with usual care, the ICERs for a sex-based treatment strategy with PQ7 for females from a healthcare provider perspective were $127 per DALY averted in Vietnam, $466 in Ethiopia, $1,089 in Afghanistan, and $4,443 in Indonesia. The PQ14 and referral options cost more while averting fewer DALYs than PQ7. This study provides an alternative cost-effective mode of rolling out tafenoquine in areas where initial testing with only a G6PD RDT is feasible.

BackgroundHepatitis B Virus (HBV) is transmitted from mother to child which can be prevented via birth dose vaccine combined with three follow up hepatitis B vaccines, hepatitis B immunoglobulins (HBIG), and maternal antiviral treatment with Tenofovir Disoproxil Fumarate (TDF). This study evaluates the cost effectiveness of six strategies to prevent perinatal HBV transmission in a resource limited setting (RLS) on the Thailand-Myanmar border.MethodsThe cost effectiveness of six strategies was tested by a decision tree model in R. All strategies included birth and follow up vaccinations and compared cost per infection averted against two willingness to pay thresholds: one-half and one gross domestic product (GDP) per capita. Strategies were: 1) Vaccine only, 2) HBIG after rapid diagnostic test (RDT): infants born to HBsAg+ are given HBIG, 3) TDF after RDT: HBsAg+ women are given TDF, 4) TDF after HBeAg test: HBeAg+ women are given TDF, 5) TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF, 6) HBIG & TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF and their infants are given HBIG. One-way and probabilistic sensitivity analyses were conducted on the cost-effective strategies.ResultsVaccine onlywas the least costly option withTDF after HBeAg teststrategy as the only cost-effective alternative.TDF after HBeAg testhad an incremental cost-effectiveness ratio of US$1062; which would not be considered cost-effective with the lower threshold of one-half GDP per capita. The one-way sensitivity analysis demonstrated that the results were reasonably robust to changes in single parameter values. The PSA showed thatTDF after HBeAg testhad an 84% likelihood of being cost effective at a willingness to pay threshold of one GDP per capita per infection averted.ConclusionsWe found thatTDF after HBeAg testhas the potential to be cost-effective if TDF proves effective locally to prevent perinatal HBV transmission. The cost of TDF treatment and reliability of the RDT could be barriers to implementing this strategy. WhileTDF after RDTmay be a more feasible strategy to implement in RLS,TDF after HBeAg testis a less costly option.

Focus and outcomes for participants Presented by researchers from the Australian Centre of Research Excellence in Malaria Elimination (ACREME, www.acreme.org.au), the focus of the symposium will be the application of multi-disciplinary epidemiological and statistical approaches to inform the control and elimination of malaria in the Asia-Pacific region. The epidemiology of malaria is complex as it involves multiple mosquito vectors, different malarial species (that require species-specific treatments) and emerging insecticide and antimalarial drug resistance. The symposium will provide an overview of the significance of the changing epidemiological landscape of malaria globally, and how modern epidemiological methods, such as stepped-wedge designs, multi-state modelling, within-host mechanistic mathematical models, geospatial methods and cost-effectiveness modelling applied to clinical effectiveness trials, prospective cohort studies, volunteer infection studies and national and regional data have contributed to answering the key challenges in malaria research. Specifically we will discuss evidence for effective interventions to reduce the risk of malaria transmission, the effect of recurrent episodes of malaria on risk of hospitalisation and mortality, the selection of antimalarial drug combination therapies to fast track new drugs, understanding geospatial heterogeneity of malaria transmission, and the cost-effectiveness of scenarios using different treatment regimens. Discussion of the importance of these methodologies and their findings will be contextualised in the current global malaria elimination goals. As similar transformations in epidemiological environment have occurred in other disease elimination settings, we believe this symposium will have broad appeal and that the challenges faced and the methodological solutions proposed to accelerate progress in malaria elimination will have a high degree of relevance and be useful to researchers working in global health or infectious diseases. Rationale for the symposium, including for its inclusion in the Congress Following a two-decade period of declining malaria burden due to intensified control efforts, global progress against the disease has stalled, and in some countries, malaria has resurged. Emerging parasite resistance to insecticides and antimalarial drugs has reduced the effectiveness of cornerstone malaria control interventions. Malaria endemic areas of the Greater Mekong Sub region (GMS) have set the target to eliminate malaria by 2030, however, the failure of these established interventions and transition to low-transmission endemic environments has necessitated fundamental re-evaluation of the epidemiological landscape of the disease and emphasised timely development of robust evidence for novel interventions. In order to provide evidence, a wide range of advanced multi-disciplinary methodologies have been developed and applied in many malaria epidemiology areas and we believe discussion of these in the symposium will be highly relevant given the principal theme of the 2020 WCE (Methodological Innovations in Epidemiology). Additionally, the symposium will feature research where findings have been effectively translated to national and regional policy and practice, an important theme of the 2020 WCE. Presentation program Names of presenters

Objective: To determine household and health-care provider costs associated with Plasmodium vivax infection across a range of endemic settings. Methods: We collected cost data alongside three multicentre clinical trials of P. vivax treatment in Afghanistan, Brazil, Colombia, Ethiopia, Indonesia, Philippines, Peru, Thailand and Viet Nam conducted between April 2014 to December 2017. We derived household costs from trial participant surveys administered at enrolment and again 2 weeks later to determine the costs of treatment and transportation, and the number of days that patients and their household caregivers were unable to undertake their usual activities. We determined costs of routine care by health-care providers by micro-costing the resources used to diagnose and treat P. vivax at the study sites. Findings: The mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4). Conclusion: An episode of P. vivax malaria results in high costs to households. The costs of diagnosing and treating P. vivax are important inputs for future cost-effectiveness analyses to ensure optimal allocation of resources for malaria elimination.

Background: There is a significant global burden of herpes simplex virus (HSV) related genital ulcer disease yet little is known about its impact on quality of life. This systematic review aimed to identify studies that quantitatively evaluated the effect of genital herpes on various aspects of health-related quality of life. Methods: Six databases were searched (MEDLINE, EMBASE, NHS Economic Evaluation Database, Health Technology Assessment, Database of Abstracts of Reviews of Effects, Web of Science Core Collection) for primary quality of life and economic evaluations of genital herpes from January 1, 2000 to January 7, 2021. Qualitative studies or those without primary data were excluded. Two authors independently extracted data from the publications. The study’s registration number with PROSPERO was CRD42021239410. Findings: We identified 26 relevant publications: 19 presented primary quality of life data, and seven were economic evaluations. The primary studies presented a range of condition-specific tools for describing the quality of life in individuals with genital herpes, but only one study used a direct valuation that could be used to generate utility weights. All economic evaluations of HSV infection were from high-income country settings. Most (6 of 7) focused on neonatal HSV infection with utilities adopted from studies prior to 2000. Interpretation: The extant literature on genital herpes-related quality of life is limited and requires updating. We recommend future studies be conducted in geographic- and population- diverse settings, and use preference-based condition-specific or generic-instruments to better inform economic modelling. Registration Details: The study’s registration number with PROSPERO was CRD42021239410. Funding Information: This review was funded by the World Health Organization through a grant from the US National Institute of Allergy and Infectious Diseases, National Institutes of Health. Declaration of Interests: We declare no competing interests.

Introduction This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso. Methods The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol’s iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019). Results The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31–41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0. Conclusion Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases.

Background In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites (“radical cure”) is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methods and findings Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised. Conclusions Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax., Dr. Devine and co-authors highlight the global economic burden of vivax malaria that could be reduced through investment in radical cure. Safe and effective cure could be achieved by routine screening for G6PD deficiency and treatment supervision., Author summary Why was this study done? Vivax malaria is a mosquito-borne febrile illness common in Asia, Latin America, and the Horn of Africa. Although a cause of significant morbidity, its global cost burden has not previously been estimated using country-level data. The timely elimination of vivax malaria will require widespread access to safe and effective radical cure. What did the researchers do and find? Data on the epidemiology and costs of vivax malaria to healthcare providers and households were collated to derive the annual global cost burden of vivax malaria. The potential impact of widespread provision of primaquine radical cure was quantified in terms of case incidence and costs for 44 endemic countries. The global cost of vivax malaria in 2017 was US$359 million, but this could be reduced by US$93.6 million by screening for G6PD deficiency and provision of supervised high-dose primaquine. What do these findings mean? Supervised primaquine can lead to a substantial reduction in household and global costs of vivax malaria, although the costs to healthcare providers will be higher. Novel, low-cost methods for improving adherence are needed to ensure the affordability and scale-up of radical cure.

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.

Background Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. Methods and findings A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre–policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of −12.9% (95% confidence interval [CI] −13.5% to −12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = −0.21% [95% CI −0.34 to −0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = −0.05% [95% CI −0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48–0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71–0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. Conclusions In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria., Ric Price and colleagues report on changes in Plasmodium falciparum and vivax malaria following a universal malaria treatment programme in Papua, Indonesia., Author summary Why was this study done? Multidrug-resistant malaria results in recurrent parasitaemia, a cumulative risk of anaemia, and progression to severe and fatal disease. Whilst artemisinin combination therapies (ACTs) and intravenous (IV) artesunate can reduce morbidity and mortality associated with P. falciparum malaria, they have no activity on the hypnozoite stages of P. vivax, which can relapse weeks to months following an initial infection and sustain ongoing transmission of the parasite. In Papua, Indonesia, antimalarial resistance has emerged in both P. falciparum and P. vivax. We used a prospective malariometric surveillance network to investigate the differential impact of a universal policy of ACTs for uncomplicated malaria and IV artesunate for severe malaria on the morbidity and mortality attributable to P. falciparum and P. vivax. What did the researchers do and find? After controlling for population growth and changes in treatment-seeking behaviour, the incidence of malaria after policy change fell by about 60% for P. falciparum and 40% for P. vivax. There was a 50% fall in the proportion of patients with malaria requiring admission to hospital and a 30% fall in malaria-related mortality. Bed occupancy due to admission with malaria fell by 25%. Whilst there was a small decrease in the absolute incidence of P. vivax infections over the 9-year study period, the proportion of malaria cases and malaria-attributable deaths to P. vivax increased with time. What do these findings mean? The results highlight the importance of highly effective blood schizontocidal antimalarial drugs in reducing the overall burden of drug-resistant malaria. The rising proportion of malaria due to P. vivax emphasizes the need for safe and effective drug regimens that clear both the blood and liver stages of P. vivax in malaria elimination efforts in coendemic regions.

To determine household and health-care provider costs associated withWe collected cost data alongside three multicentre clinical trials ofThe mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4).An episode ofDéterminer les coûts, pour les ménages et les prestataires de soins, associés à l'infection parNous avons recueilli des données sur les coûts à l'occasion de trois essais cliniques multicentres relatifs au traitement contreLes coûts totaux moyens pour les ménages allaient de 8,7 dollars des États-Unis ($ US; écart type, ET: 4,3) en Afghanistan à 254,7 $ US (ET: 148,4) en Colombie. Tous pays confondus, les pertes de productivité étaient la principale composante des coûts pour les ménages, puisqu'elles entraînaient des coûts indirects moyens allant de 5,3 $ US (ET: 3,0) à 220,8 $ US (ET: 158,40). En ce qui concerne les prestataires de soins, le coût des soins courants allait de 3,6 à 6,6 $ US. Le coût de réalisation d'un test de diagnostic rapide basé sur le glucose-6-phosphate-déshydrogénase variait de 0,9 $ US à 13,5 $ US, un coût toujours inférieur à celui du très répandu test par fluorescence (6,3 $ US à 17,4 $ US).Un épisode de paludisme àDeterminar los costos del hogar y de los proveedores de atención de la salud asociados con la infección porSe recopilaron datos de costos junto con tres ensayos clínicos multicéntricos del tratamiento conLos costos totales promedio de los hogares oscilaron entre 8,7 dólares estadounidenses (USD; desviación estándar, DE: 4,3) en Afganistán y 254,7 USD (DE: 148,4) en Colombia. En todos los países, las pérdidas de productividad fueron el mayor componente del costo del hogar, lo que dio lugar a costos indirectos promedios que oscilaron entre 5,3 y 220,8 USD. El rango de los costos de los proveedores de atención de la salud para la atención de rutina fue de 3,6 a 6,6 USD. El costo por administrar una prueba de diagnóstico rápido de la glucosa-6-fosfato-deshidrogenasa, varió de 0,9 a 13,5 USD, consistentemente más bajo que los costos de la prueba de fluorescencia aleatoria ampliamente utilizada (6,3 a 17,4 USD).Un episodio de malaria porتحديد تكاليف مزود الرعاية الصحية والتكاليف الأسرية المرتبطة بعدوى بلازموديوم فيفاكس عبر مجموعة من الأوضاع الوبائية.قمنا بتجميع بيانات التكلفة إلى جانب ثلاث تجارب سريرية متعددة المراكز لعلاج بلازموديوم فيفاكس في كل من إثيوبيا وأفغانستان وإندونيسيا والبرازيل والفلبين وبيرو وتايلند وفييت نام وكولومبيا، تمت ما بين أبريل/نيسان 2014 إلى ديسمبر/كانون أول 2017. وحصلنا على التكاليف الأسرية من مسوح للمشاركين في التجربة تم إجراؤها عند التسجيل، ثم مرة أخرى بعد أسبوعين من تحديد تكاليف العلاج والنقل، وعدد الأيام التي لم يتمكن فيها المرضى ومقدمو الرعاية المنزلية من القيام بأنشطتهم المعتادة. قمنا بتحديد تكاليف الرعاية الروتينية من جانب مقدمي الرعاية الصحية عن طريق تقدير التكاليف الدقيقة للموارد المستخدمة لتشخيص وعلاج بلازموديوم فيفاكس في مواقع الدراسة. النتائج تراوح متوسط ​​إجمالي تكاليف الأسرة من 8.7 دولاراً أمريكياً (دولار أمريكي؛ الانحراف المعياري: 4.3) في أفغانستان إلى 254.7 دولاراً أمريكياً (الانحراف المعياري: 148.4) في كولومبيا. في كل البلدان، كانت خسائر الإنتاجية هي أكبر عنصر في التكلفة الأسرية، مما أسفر عن أن يتراوح متوسط التكاليف غير المباشرة من 5.3 دولار أمريكي (الانحراف المعياري: 3.0) إلى 220.8 دولاراً أمريكياً (الانحراف المعياري: 158.40). كان نطاق تكاليف مقدم الرعاية الصحية للرعاية الروتينية يتراوح بين 3.6 و6.6 دولاراً أمريكياً. تراوحت تكلفة إجراء الاختبار التشخيصي السريع للجلوكوز 6 فوسفات ديهيدروجينيز، ما بين 0.9 إلى 13.5 دولارًا أمريكيًا، وهي أقل بشكل متسق عن تكاليف اختبار بقعة الفلورسنت المستخدم بشكل شائع (6.3 دولار أمريكي إلى 17.4 دولاراً أمريكياً).تؤدي نوبة الإصابة بملاريا确定多个流行国家我们收集了从 2014 年 4 月至 2017 年 12 月在阿富汗、埃塞俄比亚、秘鲁、巴西、菲律宾、哥伦比亚、泰国、印度尼西亚和越南进行的三项各国的平均家庭总成本分别从阿富汗的 8.7 美元(美元;标准差:4.3)至哥伦比亚的 254.7 美元(标准差:148.4)不等。在所有国家中,生产力下降是家庭成本中最主要的部分,从而导致平均间接成本从 5.3 美元(标准差:3.0)至 220.8 美元(标准差:158.40)不等。医疗护理提供者进行一般性医疗的费用范围是 3.6–6.6 美元。进行葡萄糖-6-磷酸脱氢酶快速诊断测试的费用从 0.9 美元至 13.5 美元不等,比普遍使用的荧光点试验的费用(6.3 美元至 17.4 美元)要低。.Определение затрат поставщиков услуг в сфере здравоохранения и семей пациентов при всплесках малярии, вызваннойАвторы собрали данные по затратам для трех многоцентровых клинических исследований по лечению инфекцииСредняя общая величина затрат семьи находилась в диапазоне от 8,7 долл. США (среднеквадратичное отклонение, СО 4,3) в Афганистане до 254,7 долл. США (СО 148,4) в Колумбии. Во всех странах потеря трудоспособности составляла наибольший компонент затрат семьи, при этом средние косвенные затраты составляли от 5,3 долл. США (СО 3,0) до 220,8 долл. США (СО 158,4). Затраты медицинских учреждений на обеспечение стандартного набора медицинских услуг составляли от 3,6 до 6,6 долл. США. Затраты на проведение экспресс-теста для диагностики заболевания по глюкозо-6-фосфат-дегидрогеназе составляли от 0,9 до 13,5 долл. США, что было во всех случаях ниже затрат на широко используемый тест флуоресцентного пятна (от 6,3 до 17,4 долл. США).Вспышка заболеваемости малярией, вызванной

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.

Background The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. Methods and findings Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004–15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47–0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80–2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention. Conclusions In this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482)., Paul Agius and colleagues study a topical insect repellent for protection against malaria., Author summary Why was this study done? Despite there being strong evidence for efficacy of topical repellent in preventing mosquito bites, there is a paucity of high-quality evidence for the effectiveness of repellent in reducing malaria. Topical repellents may be highly relevant in the Greater Mekong Subregion (GMS), where malaria vectors bite outdoors and are not confined to biting at night (and thus not covered by conventional vector control measures). We wanted to know whether distributing repellent through established village health volunteer (VHV) networks in the GMS would prevent malaria infection. What did the researchers do and find? We randomised 116 villages in Myanmar to receive repellent through VHV networks using a stepped-wedge design and followed the villages up for 15 months to detect malaria by rapid diagnostic test (RDT) and highly sensitive polymerase chain reaction (PCR). We found that distribution of repellent through the VHV network did not reduce RDT-detectable infection, but appeared to reduce the odds of PCR-detectable infection. The apparent protective effect of repellent was consistent across risk groups (village residents, forest dwellers, and migrants) and villages, suggesting that repellent distributed by VHVs may be an effective intervention across a range of transmission settings and populations. What do these findings mean? Distribution of topical repellent by the VHV network may be an effective supplementary intervention for reducing malaria in the GMS. Incorporation of repellent into national malaria control programme national strategic plans for malaria elimination may advance achieving GMS malaria elimination targets of 2025 for P. falciparum and 2030 for all malaria species, particularly in the context of limited effectiveness of traditional vector control interventions and spreading drug resistance. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform World Health Organization public health policy on the deployment of topical repellents for malaria prevention.

The control and eventual elimination of malaria will require widescale adoption of strategies to ensure early diagnosis and highly effective treatment of infected individuals. In Plasmodium vivax, multiple relapse episodes can only be averted by treating the dormant liver stage of the parasite life cycle - a strategy known as radical cure. This thesis aims to investigate key factors determining treatment-seeking behaviour and costs associated with vivax malaria, how these influence healthcare decisions, the cost-effectiveness of screening tests and treatments for radical cure, and the cost-benefit implications of their global implementation.Treatment-seeking behaviour, assessed in Papua, Indonesia, demonstrated that household costs per person seeking treatment for vivax malaria were similar to those for falciparum malaria. Switching from ineffective to effective malaria treatment in the public sector improved the behaviour of patients and both public and private healthcare providers. Diagnostic strategies were investigated on the Thai-Myanmar border, where screening for glucose-6-phosphate-dehydrogenase (G6PD) deficiency prior to radical cure reduced the disease burden while being a cost-effective option for healthcare providers that do not use radical cure and a potentially cost-saving alternative where primaquine is prescribed without screening. The costs of implementing G6PD screening were collected in three countries, and highlighted that RDTs consistently reduced costs as compared to the widely-used fluorescent spot test. Across four countries, the indirect cost due to lost productivity was the largest cost component for households of patients with vivax malaria. After combining provider and patient costs with case estimates, the global economic burden of vivax malaria was estimated to be US\$330 million per year. Adopting a policy of screening for G6PD deficiency with delivery of highly effective radical cure was projected to save US\$45 million.P. vivax malaria causes a large economic burden that can be reduced substantially by delivering safe and effective radical cure.

Background Data on the cost effectiveness of hepatitis B virus (HBV) screening and vaccination strategies for prevention of vertical transmission of HBV in resource limited settings is sparse. Methods A decision tree model of HBV prevention strategies utilised data from a cohort of 7071 pregnant women on the Thailand-Myanmar border using a provider perspective. All options included universal HBV vaccination for newborns in three strategies: (1) universal vaccination alone; (2) universal vaccination with screening of women during antenatal visits with rapid diagnostic test (RDT) plus HBV immune globulin (HBIG) administration to newborns of HBV surface antigen positive women; and (3) universal vaccination with screening of women during antenatal visits plus HBIG administration to newborns of women testing HBV e antigen positive by confirmatory test. At the time of the study, the HBIG after confirmatory test strategy was used. The costs in United States Dollars (US$), infections averted and incremental cost effectiveness ratios (ICERs) were calculated and sensitivity analyses were conducted. A willingness to pay threshold of US$1200 was used. Results The universal HBV vaccination was the least costly option at US$4.33 per woman attending the clinic. The HBIG after (RDT) strategy had an ICER of US$716.78 per infection averted. The HBIG after confirmatory test strategy was not cost-effective due to extended dominance. The one-way sensitivity analysis showed that while the transmission parameters and cost of HBIG had the biggest impact on outcomes, the HBIG after confirmatory test only became a cost-effective option when a low test cost was used or a high HBIG cost was used. The probabilistic sensitivity analysis showed that HBIG after RDT had an 87% likelihood of being cost-effective as compared to vaccination only at a willingness to pay threshold of US$1200. Conclusions HBIG following confirmatory test is not a cost-effective strategy for preventing vertical transmission of HBV in the Thailand-Myanmar border population. By switching to HBIG following rapid diagnostic test, perinatal infections will be reduced by nearly one third. This strategy may be applicable to similar settings for marginalized populations where the confirmatory test is not logistically possible. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2660-x) contains supplementary material, which is available to authorized users.

Background Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs) offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings. Methods/Principal findings Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs) associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1) giving chloroquine alone and (2) giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar. Conclusions/Significance In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values, including the mortality rates for both primaquine-induced hemolysis and P. vivax. The online model provides an opportunity to use different parameter estimates to examine the validity of these findings in other settings., Author summary A single infection with Plasmodium vivax can cause multiple episodes of illness due to dormant liver parasites called hypnozoites. Primaquine is the only drug currently available to treat hypnozoites but is under-used because it can cause life-threatening red blood cell damage in people who have an inherited condition called glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other locations, primaquine is given without testing for G6PD deficiency, putting patients at risk of potentially fatal hemolysis. New rapid diagnostic tests provide the opportunity to screen for G6PD deficiency prior to giving patients primaquine. Our study describes a cost-effectiveness analysis conducted using data gathered from the Thailand-Myanmar border. Our results show that screening for G6PD deficiency followed by primaquine treatment provided a few days of disability-free health per patient treated. This was achieved for similar costs as not giving primaquine to anyone or cost savings when compared to giving primaquine without screening. In addition to the health gains provided to patients, the safe use of primaquine will be a critical tool to eliminate malaria. We provide an interactive cost-effectiveness tool online that can be adapted to other locations to examine the potential costs and benefits of using rapid diagnostic tests for G6PD in different scenarios.

Objective:\ud Proxy measures are an alternative source of data for care home residents who are unable to complete the health utility measure, but the agreement levels between residents and care home staff for the EQ-5D have not been investigated previously. The objective of the present study was to examine the inter-rater agreement levels for the reporting of EQ-5D by care home residents and staff, adjusting for the impact of clustering.\ud \ud Study Design and Setting:\ud The data consist of EQ-5D scores for 565 pairs of care home residents and proxies and quality-adjusted life-years (QALYs) for 248 pairs. Cluster-adjusted agreement was compared for the domains, index scores, and QALYs from the EQ-5D. Factors influencing index score agreement are also described.\ud \ud Results:\ud The results show poor to fair agreement at the domain level (cluster-adjusted Kappa −0.03 to 0.26) and moderate agreement at the score level (cluster-adjusted intra-class correlation coefficient [ICC] 0.44–0.50) and for QALYs (cluster-adjusted ICC 0.59). A higher likelihood of depression and lower cognitive impairment were both associated with smaller discrepancy between proxy and self-completed scores.\ud \ud Conclusion:\ud Proxies appear to be an acceptable source of data for index scores and QALYs but may be less reliable if individual domains are considered.

Summary Background Depression is common and is associated with poor outcomes among elderly care-home residents. Exercise is a promising low-risk intervention for depression in this population. We tested the hypothesis that a moderate intensity exercise programme would reduce the burden of depressive symptoms in residents of care homes. Methods We did a cluster-randomised controlled trial in care homes in two regions in England; northeast London, and Coventry and Warwickshire. Residents aged 65 years or older were eligible for inclusion. A statistician independent of the study randomised each home (1 to 1·5 ratio, stratified by location, minimised by type of home provider [local authority, voluntary, private and care home, private and nursing home] and size of home [

Background Better self management could improve quality of life (QoL) and reduce hospital admissions in chronic obstructive pulmonary disease (COPD), but the best way to promote it remains unclear. Aim To explore the feasibility, effectiveness and cost effectiveness of a novel, layperson-led, theoretically driven COPD self-management support programme. Design and setting Pilot randomised controlled trial in one UK primary care trust area. Method Patients with moderate to severe COPD were identified through primary care and randomised 2:1 to the 7-week-long, group intervention or usual care. Outcomes at baseline, 2, and 6 months included self-reported health, St George’s Respiratory Questionnaire (SGRQ), EuroQol, and exercise. Results Forty-four per cent responded to GP invitation, 116 were randomised: mean (standard deviation [SD]) age 69.5 (9.8) years, 46% male, 78% had unscheduled COPD care in the previous year. Forty per cent of intervention patients completed the course; 35% attended no sessions; and 78% participants completed the 6-month follow-up questionnaire. Results suggest that the intervention may increase both QoL (mean EQ-5D change 0.12 (95% confidence interval [CI] = –0.02 to 0.26) higher, intervention versus control) and exercise levels, but not SGRQ score. Economic analyses suggested that with thresholds of £20 000 per quality-adjusted life-year gained, the intervention is likely to be cost-effective. Conclusion This intervention has good potential to meet the UK National Institute for Health and Clinical Excellence criteria for cost effectiveness, and further research is warranted. However, to make a substantial impact on COPD self-management, it will also be necessary to explore other ways to enable patients to access self-management education.

Background Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. Design This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8 weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. Discussion This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir. Trial registration ClinicalTrials.gov Identifier: NCT01814683. Registered March 18, 2013 Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1276-2) contains supplementary material, which is available to authorized users.

BACKGROUND: The Partners in Prevention HSV/HIV transmission trial (Partners HSV/HIV Transmission Study) showed that herpes simplex virus-2 (HSV-2) suppressive therapy with daily aciclovir could decrease HIV disease progression amongst HIV-1/HSV-2 coinfected individuals. The cost-effectiveness of daily aciclovir for delaying HIV-1 disease progression in women not eligible for antiretroviral therapy (ART) is estimated. METHODS: Resource use/cost data for delivering daily aciclovir at a primary health care HIV clinic were collected in Johannesburg. Effectiveness estimates were obtained from the Partners HSV/HIV Transmission Study trial and epidemiologic data from South Africa. A Markov model simulated the cost-effectiveness of daily aciclovir on HIV-1 disease progression in ART-naive women. Therapy was given to all HIV-1-infected women. Cost-effectiveness was compared against cost per life-year gained ( approximately US $1200 per LYG) of ART provision in South Africa. RESULTS: For an ART eligibility criteria of CD4 count

The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0896-8) contains supplementary material, which is available to authorized users.

There has been discussion about whether individuals coinfected with HIV and hepatitis C virus (HCV) or hepatitis B virus (HBV) (∼30% of all people living with HIV) should be prioritized for early HIV antiretroviral therapy (ART). We assess the relative benefits of providing ART at CD4 count below 500 cells/μl or immediate ART to HCV/HIV or HBV/HIV-coinfected adults compared with HIV-monoinfected adults. We evaluate individual outcomes (HIV/liver disease progression) and preventive benefits in a generalized HIV epidemic setting.We modeled disease progression for HIV-monoinfected, HBV/HIV-coinfected, and HCV/HIV-coinfected adults for differing ART eligibility thresholds (CD4350 cells/μl, CD4500 cells/μl, immediate ART eligibility upon infection). We report disability-adjusted life-years averted per 100 person-years on ART (DALYaverted/100PYonART) as a measure of the health benefits generated from incremental changes in ART eligibility. Sensitivity analyses explored impact on sexual HIV and vertical HIV, HCV, and HBV transmission.For HBV/HIV-coinfected adults, a switch to ART initiation at CD4 count below 500 cells/μl from CD4 below 350 cells/μl generates 9% greater health benefits per year on ART (48 DALYaverted/100PYonART) than for HIV-monoinfected adults (44 DALYaverted/100PYonART). Additionally, ART at CD4 below 500 cells/μl could prevent 25% and 32% of vertical transmissions of HIV and HBV, respectively. For HCV/HIV-coinfected adults, ART at CD4 below 500 cells/μl generates 10% fewer health benefits (40 DALYaverted/100PYonART) than for HIV monoinfection, unless ART reduces progression to cirrhosis by more than 70% (33% in base-case).The additional therapeutic benefits of ART for HBV-related liver disease results in ART generating more health benefits among HBV/HIV-coinfected adults than HIV-monoinfected individuals, whereas less health benefits are generated amongst HCV/HIV coinfection in a generalized HIV epidemic setting.

Background: Many older people living in care homes (long term residential care or nursing homes) are depressed. Exercise is a promising non-drug intervention for preventing and treating depression in this population. Objective: To evaluate the impact of a ‘whole-home’ intervention, consisting of training for residential and nursing home staff backed up with a twice-weekly, physiotherapist-led exercise class on depressive symptoms in care home residents. Design: A cluster randomised controlled trial with a cost-effectiveness analysis to compare (1) the prevalence of depression in intervention homes with that in control homes in all residents contributing data 12 months after homes were randomised (cross-sectional analysis); (2) the number of depressive symptoms at 6 months between intervention and control homes in residents who were depressed at pre-randomisation baseline assessment (depressed cohort comparison); and (3) the number of depressive symptoms at 12 months between intervention and control homes in all residents who were present at pre-randomisation baseline assessment (cohort comparison). Setting: Seventy-eight care homes in Coventry and Warwickshire and north-east London. Participants: Care home residents aged ≥ 65 years. Interventions: Control intervention: Depression awareness training programme for care home staff. Active intervention: A ‘whole-home’ exercise intervention, consisting of training for care home staff backed up with a twice-weekly, physiotherapist-led exercise group. Main outcome measures: Geriatric Depression Scale-15, proxy European Quality of Life-5 Dimensions (EQ-5D), cost-effectiveness from an National Health Service perspective, peripheral fractures and death. Results: We recruited a total of 1054 participants. Cross-sectional analysis: We obtained 595 Geriatric Depression Scale-15 scores and 724 proxy EQ-5D scores. For the cohort analyses we obtained 765 baseline Geriatric Depression Scale-15 scores and 776 proxy EQ-5D scores. Of the 781 who we assessed prior to randomisation, 765 provided a Geriatric Depression Scale-15 score. Of these 374 (49%) were depressed and constitute our depressed cohort. Resource-use and quality-adjusted life-year data, based on proxy EQ-5D, were available for 798 residents recruited prior to randomisation. We delivered 3191 group exercise sessions with 31,705 person attendances and an average group size of 10 (5.3 study participants and 4.6 non-study participants). On average, our participants attended around half of the possible sessions. No serious adverse events occurred during the group exercise sessions. In the cross-sectional analysis the odds for being depressed were 0.76 [95% confidence interval (CI) 0.53 to 1.09] lower in the intervention group at 12 months. The point estimates for benefit for both the cohort analysis (0.13, 95% CI −0.33 to 0.60) and depressed cohort (0.22, 95% CI −0.52 to 0.95) favoured the control intervention. There was no evidence of differences in fracture rates or mortality (odds ratio 1.07, 95% CI 0.79 to 1.48) between the two groups. There was no evidence of differences in the other outcomes between the two groups. Economic analysis: The additional National Health Service cost of the OPERA intervention was £374 per participant (95% CI −£655 to £1404); the mean difference in quality-adjusted life-year was −0.0014 (95% CI −0.0728 to 0.0699). The active intervention was thus dominated by the control intervention, which was more effective and less costly. Conclusion: The results do not support the use of a whole-home physical activity and moderate-intensity exercise programme to reduce depression in care home residents. Trial registration: Current Controlled Trials ISRCTN43769277. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 18. See the Health Technology Assessment programme website for further project information.

Objective The Identification and Referral to Improve Safety (IRIS) cluster randomised controlled trial tested the effectiveness of a training and support intervention to improve the response of primary care to women experiencing domestic violence (DV). The aim of this study is to estimate the cost-effectiveness of this intervention. Design Markov model-based cost-effectiveness analysis. Setting General practices in two urban areas in the UK. Participants Simulated female individuals from the general UK population who were registered at general practices, aged 16 years and older. Intervention General practices received staff training, prompts to ask women about DV embedded in the electronic medical record, a care pathway including referral to a specialist DV agency and continuing contact from that agency. The trial compared the rate of referrals of women with specialist DV agencies from 24 general practices that received the IRIS programme with 24 general practices not receiving the programme. The trial did not measure outcomes for women beyond the intermediate outcome of referral to specialist agencies. The Markov model extrapolated the trial results to estimate the long-term healthcare and societal costs and benefits using data from other trials and epidemiological studies. Results The intervention would produce societal cost savings per woman registered in the general practice of UK£37 (95% CI £178 saved to a cost of £136) over 1 year. The incremental quality-adjusted life-year was estimated to be 0.0010 (95% CI −0.0157 to 0.0101) per woman. Probabilistic sensitivity analysis found 78% of model replications under a willingness to pay threshold of £20 000 per quality-adjusted life-year. Conclusions The IRIS programme is likely to be cost-effective and possibly cost saving from a societal perspective. Better data on the trajectory of abuse and the effect of advocacy are needed for a more robust model. Trial registration Current Controlled Trials, ISRCTN74012786., Article summary Article focus The aim of this study was to assess the cost-effectiveness of the IRIS training and support intervention for primary care clinicians from the UK societal and NHS perspectives. Key messages The intervention is likely to be cost saving from a societal perspective with a high likelihood of being under a £20 000 per quality-adjusted life-year willingness to pay threshold. Strengths and limitations of this study We have minimised bias in estimating the effect size of the IRIS programme by basing it on a randomised controlled trial. By using epidemiological and cost data external to the trial, we were able to extrapolate from directly measured trial outcomes (DV disclosure and referral rates) to quality of life, health and economic outcomes. The uncertainty of the transition probabilities based on assumptions was addressed by probabilistic sensitivity analysis, contributing to the robustness of the model. Important limitations of that data are the paucity of longitudinal studies measuring the trajectory of abuse and uncertainty about the effect of DV advocacy for women not living in a refuge or shelter.

Background Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life. Methods In an ethnically stratified randomised controlled trial conducted at St Mary’s Hospital London, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25(OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child’s electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses. Results We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95%CI -2.63, 1.06; adjusted –1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial. Conclusions We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years. Trial Registration Controlled-Trials.com ISRCTN68645785

Intimate partner violence (IPV) creates a substantial burden of disease and significant costs to families, communities, and governments. Building the evidence for effective interventions to reduce violence and its sequelae requires increased use of economic evaluation to inform policy through the analysis of costs and potential savings of interventions. The authors review existing economic evaluations and present case studies of current research from the United Kingdom and Australia to illustrate the strengths and limitations of two approaches to generating economic evidence: economic evaluation alongside randomized controlled trials and economic modeling. Economic evaluation should always be considered in the design of IPV intervention research.