The economic burden of congenital Zika Syndrome in Brazil: an overview at 5 years and 10 years.

BACKGROUND: The aim of this paper is to estimate the economic burden of children with congenital Zika Syndrome (CZS) in Brazil over 5-10 years. METHODS: We conducted a modelling study based on data collected in a case-control study in Brazil, including children with CZS (cases) and typically developing children (controls), born in 2015 and 2016. In total, 484 participants were recruited in two sites, Recife and Rio de Janeiro. Social and economic information was collected in a survey from the carers of cases and controls, and detailed healthcare utilisation was recorded for each child in the Rio de Janeiro cohort prospectively in a database. We used this information to estimate the cost per child with severe, moderate and no CZS and incremental cost per child with severe and moderate versus no CZS from a disaggregated societal perspective. These estimates were incorporated into an economic burden model to estimate the incremental burden of the CZS epidemic in Brazil over 5 years and 10 years. FINDINGS: The societal cost per child with severe CZS was US$50 523 to 10 years of age (born in 2015 and 2016), substantially higher than the costs for moderate CZS (US$29 283) and without CZS (US$12 331). The incremental economic burden of severe versus no CZS in Brazil over 10 years was US$69.4 million from the household and US$129.0 million from the government perspective. For moderate CZS, these figures amounted to US$204.1 million and US$86.6 million. Over 10 years, 97% of the total societal economic cost of severe CZS is borne by the government, but only 46% for moderate CZS. INTERPRETATION: The economic burden of CZS is high at the household, provider and government levels. The compensatory government payments helped to alleviate some of the additional costs incurred by families with a child qualifying for the disability benefits, and could be scaled to include the children with moderate CZS.

Towards universal health coverage for people with stroke in South Africa: a scoping review.

OBJECTIVES: To explore the opportunities and challenges within the health system to facilitate the achievement of universal health coverage (UHC) for people with stroke (PWS) in South Africa (SA). SETTING: SA. DESIGN: Scoping review. SEARCH METHODS: We conducted a scoping review of opportunities and challenges to achieve UHC for PWS in SA. Global and Africa-specific databases and grey literature were searched in July 2020. We included studies of all designs that described the healthcare system for PWS. Two frameworks, the Health Systems Dynamics Framework and WHO Framework, were used to map data on governance and regulation, resources, service delivery, context, reorientation of care and community engagement. A narrative approach was used to synthesise results. RESULTS: Fifty-nine articles were included in the review. Over half (n=31, 52.5%) were conducted in Western Cape province and most (n=41, 69.4%) were conducted in urban areas. Studies evaluated a diverse range of health system categories and various outcomes. The most common reported component was service delivery (n=46, 77.9%), and only four studies (6.7%) evaluated governance and regulation. Service delivery factors for stroke care were frequently reported as poor and compounded by context-related limiting factors. Governance and regulations for stroke care in terms of government support, investment in policy, treatment guidelines, resource distribution and commitment to evidence-based solutions were limited. Promising supporting factors included adequately equipped and staffed urban tertiary facilities, the emergence of Stroke units, prompt assessment by health professionals, positive staff attitudes and care, two clinical care guidelines and educational and information resources being available. CONCLUSION: This review fills a gap in the literature by providing the range of opportunities and challenges to achieve health for all PWS in SA. It highlights some health system areas that show encouraging trends to improve service delivery including comprehensiveness, quality and perceptions of care.

[Catastrophic expenditure on congenital Zika syndrome: results of a cross-sectional study of caregivers of children in Rio de Janeiro, Brazil]. / Gasto catastrófico na síndrome congênita do vírus Zika: resultados de um estudo transversal com cuidadores de crianças no Rio de Janeiro, Brasil.

In 2015, there was an increase in cases of congenital malformations in newborns in Brazil, associated with maternal Zika virus infection, having serious social and economic repercussions for the families. The study aimed to estimate the prevalence of catastrophic expenditure by families of children with severe or mild/moderate congenital Zika syndrome (CZS) in comparison to families of children without a diagnosis of CZS in the state of Rio de Janeiro. Catastrophic expenditure occurs when spending exceeds a given proportion of the family income due to a disease. Family caregivers of children with severe CZS were younger and had less schooling and lower income. Prevalence of catastrophic expenditure was higher in families of children with CZS. Among caregivers of children with severe CZS, the prevalence of catastrophic expenditure was higher in those with severe or very severe depression, anxiety, and stress. Low social support among caregivers was also a determinant factor for increased prevalence of catastrophic expenditure. The burden on caregivers of children with severe CZS exacerbates a situation of vulnerability that requires the expansion of mechanisms for financial and social protection, through linkage of various policies capable of effectively reaching this group.

Em 2015, houve um aumento de casos de más-formações congênitas entre recém-nascidos no Brasil associado ao vírus Zika, com repercussões sociais e econômicas para as famílias. O objetivo deste estudo foi estimar a prevalência de gasto catastrófico para famílias de crianças com síndrome congênita do vírus Zika (SCZ) grave, leve/moderada em comparação com famílias de crianças sem diagnóstico de SCZ, no Estado do Rio de Janeiro. O termo gasto catastrófico ocorre quando o gasto excede determinada proporção da renda da família devido à doença. Os cuidadores de crianças com SCZ grave eram mais jovens, com menor escolaridade e renda. A prevalência de gasto catastrófico foi maior em famílias de crianças com SCZ. Dentre os cuidadores de crianças com SCZ grave, identificou-se que a prevalência de gasto catastrófico foi mais elevada entre aqueles que apresentaram graus de depressão, ansiedade e estresse graves ou muito graves. O baixo apoio social entre os cuidadores também foi determinante para o aumento da prevalência do gasto. A carga que incide sobre os cuidadores de crianças com SCZ grave potencializa uma situação de vulnerabilidade que demanda a amplificação do acesso aos mecanismos de proteção financeira e social, através da articulação de diferentes políticas que sejam capazes de alcançar efetivamente esse grupo.

En 2015, hubo un aumento de casos de malformaciones congénitas entre recién nacidos en Brasil, asociado al virus zika con repercusiones sociales y económicas para las familias. El objetivo de este estudio fue estimar la prevalencia de gasto catastrófico para las familias de niños con síndrome congénito del virus Zika (SCZ) grave, leve/moderado, en comparación con familias de niños sin diagnóstico de SCZ, en el estado de Río de Janeiro. El término gasto catastrófico se usa cuando el gasto excede una determinada proporción de la renta de la familia, debido a la enfermedad. Los cuidadores de niños con SCZ grave eran más jóvenes, con menor escolaridad y renta. La prevalencia de gasto catastrófico fue mayor en familias de niños con SCZ. Entre los cuidadores de niños con SCZ grave se identificó que la prevalencia de gasto catastrófico fue más elevada entre aquellos que presentaron grados de depresión, ansiedad y estrés grave o muy grave. El bajo apoyo social entre los cuidadores también fue determinante para el aumento de la prevalencia del gasto. La carga que incide sobre los cuidadores de niños con SCZ grave potencia una situación de vulnerabilidad que demanda la ampliación del acceso a los mecanismos de protección financiera y social, a través de la coordinación de diferentes políticas que sean capaces de alcanzar efectivamente a ese grupo.

Gasto catastrófico na síndrome congênita do vírus Zika: resultados de um estudo transversal com cuidadores de crianças no Rio de Janeiro, Brasil / Catastrophic expenditure on congenital Zika syndrome: results of a cross-sectional study of caregivers of children in Rio de Janeiro, Brazil / Gasto catastrófico en el síndrome congénito del virus Zika: resultados de un estudio transversal con cuidadores de niños en Río de Janeiro, Brasil

Em 2015, houve um aumento de casos de más-formações congênitas entre recém-nascidos no Brasil associado ao vírus Zika, com repercussões sociais e econômicas para as famílias. O objetivo deste estudo foi estimar a prevalência de gasto catastrófico para famílias de crianças com síndrome congênita do vírus Zika (SCZ) grave, leve/moderada em comparação com famílias de crianças sem diagnóstico de SCZ, no Estado do Rio de Janeiro. O termo gasto catastrófico ocorre quando o gasto excede determinada proporção da renda da família devido à doença. Os cuidadores de crianças com SCZ grave eram mais jovens, com menor escolaridade e renda. A prevalência de gasto catastrófico foi maior em famílias de crianças com SCZ. Dentre os cuidadores de crianças com SCZ grave, identificou-se que a prevalência de gasto catastrófico foi mais elevada entre aqueles que apresentaram graus de depressão, ansiedade e estresse graves ou muito graves. O baixo apoio social entre os cuidadores também foi determinante para o aumento da prevalência do gasto. A carga que incide sobre os cuidadores de crianças com SCZ grave potencializa uma situação de vulnerabilidade que demanda a amplificação do acesso aos mecanismos de proteção financeira e social, através da articulação de diferentes políticas que sejam capazes de alcançar efetivamente esse grupo.

In 2015, there was an increase in cases of congenital malformations in newborns in Brazil, associated with maternal Zika virus infection, having serious social and economic repercussions for the families. The study aimed to estimate the prevalence of catastrophic expenditure by families of children with severe or mild/moderate congenital Zika syndrome (CZS) in comparison to families of children without a diagnosis of CZS in the state of Rio de Janeiro. Catastrophic expenditure occurs when spending exceeds a given proportion of the family income due to a disease. Family caregivers of children with severe CZS were younger and had less schooling and lower income. Prevalence of catastrophic expenditure was higher in families of children with CZS. Among caregivers of children with severe CZS, the prevalence of catastrophic expenditure was higher in those with severe or very severe depression, anxiety, and stress. Low social support among caregivers was also a determinant factor for increased prevalence of catastrophic expenditure. The burden on caregivers of children with severe CZS exacerbates a situation of vulnerability that requires the expansion of mechanisms for financial and social protection, through linkage of various policies capable of effectively reaching this group.

En 2015, hubo un aumento de casos de malformaciones congénitas entre recién nacidos en Brasil, asociado al virus zika con repercusiones sociales y económicas para las familias. El objetivo de este estudio fue estimar la prevalencia de gasto catastrófico para las familias de niños con síndrome congénito del virus Zika (SCZ) grave, leve/moderado, en comparación con familias de niños sin diagnóstico de SCZ, en el estado de Río de Janeiro. El término gasto catastrófico se usa cuando el gasto excede una determinada proporción de la renta de la familia, debido a la enfermedad. Los cuidadores de niños con SCZ grave eran más jóvenes, con menor escolaridad y renta. La prevalencia de gasto catastrófico fue mayor en familias de niños con SCZ. Entre los cuidadores de niños con SCZ grave se identificó que la prevalencia de gasto catastrófico fue más elevada entre aquellos que presentaron grados de depresión, ansiedad y estrés grave o muy grave. El bajo apoyo social entre los cuidadores también fue determinante para el aumento de la prevalencia del gasto. La carga que incide sobre los cuidadores de niños con SCZ grave potencia una situación de vulnerabilidad que demanda la ampliación del acceso a los mecanismos de protección financiera y social, a través de la coordinación de diferentes políticas que sean capaces de alcanzar efectivamente a ese grupo.

Cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine for malaria during pregnancy: an analysis using efficacy results from Uganda and Kenya, and pooled data.

BACKGROUND: Prevention of malaria infection during pregnancy in HIV-negative women currently relies on the use of long-lasting insecticidal nets together with intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Increasing sulfadoxine-pyrimethamine resistance in Africa threatens current prevention of malaria during pregnancy. Thus, a replacement for IPTp-SP is urgently needed, especially for locations with high sulfadoxine-pyrimethamine resistance. Dihydroartemisinin-piperaquine is a promising candidate. We aimed to estimate the cost-effectiveness of intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) versus IPTp-SP to prevent clinical malaria infection (and its sequelae) during pregnancy. METHODS: We did a cost-effectiveness analysis using meta-analysis and individual trial results from three clinical trials done in Kenya and Uganda. We calculated disability-adjusted life-years (DALYs) arising from stillbirths, neonatal death, low birthweight, mild and moderate maternal anaemia, and clinical malaria infection, associated with malaria during pregnancy. Cost estimates were obtained from data collected in observational studies, health-facility costings, and from international drug procurement databases. The cost-effectiveness analyses were done from a health-care provider perspective using a decision tree model with a lifetime horizon. Deterministic and probabilistic sensitivity analyses using appropriate parameter ranges and distributions were also done. Results are presented as the incremental cost per DALY averted and the likelihood that an intervention is cost-effective for different cost-effectiveness thresholds. FINDINGS: Compared with three doses of sulfadoxine-pyrimethamine, three doses of dihydroartemisinin-piperaquine, delivered to a hypothetical cohort of 1000 pregnant women, averted 892 DALYs (95% credibility interval 274 to 1517) at an incremental cost of US$7051 (2653 to 13 038) generating an incremental cost-effectiveness ratio (ICER) of $8 (2 to 29) per DALY averted. Compared with monthly doses of sulfadoxine-pyrimethamine, monthly doses of dihydroartemisinin-piperaquine averted 534 DALYS (-141 to 1233) at a cost of $13 427 (4994 to 22 895), resulting in an ICER of $25 (-151 to 224) per DALY averted. Both results were highly robust to most or all variations in the deterministic sensitivity analysis. INTERPRETATION: Our findings suggest that among HIV-negative pregnant women with high uptake of long-lasting insecticidal nets, IPTp-DP is cost-effective in areas with high malaria transmission and high sulfadoxine-pyrimethamine resistance. These data provide a comprehensive overview of the current evidence on the cost-effectiveness of IPTp-DP. Nevertheless, before a policy change is advocated, we recommend further research into the effectiveness and costs of different regimens of IPTp-DP in settings with different underlying sulfadoxine-pyrimethamine resistance. FUNDING: Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Hygiene and Tropical Medicine.

Achieving universal health coverage for people with stroke in South Africa: protocol for a scoping review.

INTRODUCTION: Stroke is the second most common cause of death after HIV/AIDS and a significant health burden in South Africa. The extent to which universal health coverage (UHC) is achieved for people with stroke in South Africa is unknown. Therefore, a scoping review to explore the opportunities and challenges within the South African health system to facilitate the achievement of UHC for people with stroke is warranted. METHODS AND ANALYSIS: The scoping review will follow the approach recommended by Levac, Colquhoun and O'Brien, which includes five steps: (1) identifying the research question, (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, and (5) collating, summarising and reporting the results. Health Systems Dynamics Framework and WHO Framework on integrated people-centred health services will be used to map, synthesise and analyse data thematically. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review, as it will only include published and publicly available data. The findings of this review will be published in an open-access, peer-reviewed journal and we will develop an accessible summary of the results for website posting and stakeholder meetings.

The association of depression, anxiety, and stress with caring for a child with Congenital Zika Syndrome in Brazil; Results of a cross-sectional study.

BACKGROUND: Zika virus (ZIKV) infection in pregnancy can cause microcephaly and a wide spectrum of severe adverse outcomes, collectively called "Congenital Zika Syndrome" (CZS). Parenting a child with disabilities can have adverse mental health impacts, but these associations have not been fully explored in the context of CZS in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken in Recife and Rio de Janeiro, including 163 caregivers of a child with CZS (cases) and 324 caregivers with an unaffected child (comparison subjects), identified from existing studies. The primary caregiver, almost always the mother, was interviewed using a structured questionnaire to collect information on: depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-DASS-21), social support (Medical Outcomes Study Social Support Scale-MOS-SSS), and socio-demographic data. Data was collected May 2017-January 2018. Ethical standards were adhered to throughout the research. A high proportion of mothers reported experiencing severe or extremely severe levels of depression (18%), anxiety (27%) and stress (36%). Mothers of children with CZS were more likely to experience symptoms of depression, anxiety andstress, compared to mothers of comparison children. These associations were more apparent among mothers living in Rio de Janeiro. These differences were reduced after adjustment for socio-economic status and social support. Among mothers of children with CZS, low social support was linked to higher levels of depression, anxiety and stress, but there was no association with socio-economic status. CONCLUSIONS/SIGNIFICANCE: Depression, anxiety and stress were very common among mothers of young children in Brazil, regardless of whether they were parenting a child with disabilities. Mothers of children with CZS may be particularly vulnerable to poor mental health, and this association may be buffered through better social support.

Patients' costs, socio-economic and health system aspects associated with malaria in pregnancy in an endemic area of Colombia.

Malaria in pregnancy threatens birth outcomes and the health of women and their newborns. This is also the case in low transmission areas, such as Colombia, where Plasmodium vivax is the dominant parasite species. Within the Colombian health system, which underwent major reforms in the 90s, malaria treatment is provided free of charge to patients. However, patients still incur costs, such as transportation and value of time lost due to the disease. We estimated such costs among 40 pregnant women with clinical malaria (30% Plasmodium falciparum, 70% Plasmodium vivax) in the municipality of Tierralta, Northern Colombia. In a cross-sectional study, women were interviewed after an outpatient or inpatient laboratory confirmed malaria episode. Women were asked to report all types of cost incurred before (including prevention), during and immediately after the contact with the health facility. Median total cost was over 16US$ for an outpatient visit, rising to nearly 30US$ if other treatments were sought before reaching the health facility. Median total inpatient cost was 26US$ or 54US$ depending on whether costs incurred prior to admission were excluded or included. For both outpatients and inpatients, direct costs were largely due to transportation and indirect costs constituted the largest share of total costs. Estimated costs are likely to represent only one of the constraints that women face when seeking treatment in an area characterized, at the time of the study, by armed conflict, displacement, and high vulnerability of indigenous women, the group at highest risk of malaria. Importantly, the Colombian peace process, which culminated with the cease-fire in August 2016, may have a positive impact on achieving universal access to healthcare in conflict areas. The current study can inform malaria elimination initiatives in Colombia.

A bibliometric analysis of systematic reviews on vaccines and immunisation.

INTRODUCTION: SYSVAC is an online bibliographic database of systematic reviews and systematic review protocols on vaccines and immunisation compiled by the London School of Hygiene & Tropical Medicine and hosted by the World Health Organization (WHO) through their National Immunization Technical Advisory Groups (NITAG) resource centre (www.nitag-resource.org). Here the development of the database and a bibliometric review of its content is presented, describing trends in the publication of policy-relevant systematic reviews on vaccines and immunisation from 2008 to 2016. MATERIALS AND METHODS: Searches were conducted in seven scientific databases according to a standardized search protocol, initially in 2014 with the most recent update in January 2017. Abstracts and titles were screened according to specific inclusion criteria. All included publications were coded into relevant categories based on a standardized protocol and subsequently analysed to look at trends in time, topic, area of focus, population and geographic location. RESULTS: After screening for inclusion criteria, 1285 systematic reviews were included in the database. While in 2008 there were only 34 systematic reviews on a vaccine-related topic, this increased to 322 in 2016. The most frequent pathogens/diseases studied were influenza, human papillomavirus and pneumococcus. There were several areas of duplication and overlap. DISCUSSION: As more systematic reviews are published it becomes increasingly time-consuming for decision-makers to identify relevant information among the ever-increasing volume available. The risk of duplication also increases, particularly given the current lack of coordination of systematic reviews on vaccine-related questions, both in terms of their commissioning and their execution. The SYSVAC database offers an accessible catalogue of vaccine-relevant systematic reviews with, where possible access or a link to the full-text. CONCLUSIONS: SYSVAC provides a freely searchable platform to identify existing vaccine-policy-relevant systematic reviews. Systematic reviews will need to be assessed adequately for each specific question and quality.

Prevention of malaria in pregnancy.

Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012. Although resistance to sulfadoxine-pyrimethamine reduces the parasitological efficacy of IPTp, this drug combination remains associated with reduced incidence of low birthweight in areas where prevalence of parasites with quintuple Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations is greater than 90%. Nevertheless, its effectiveness is compromised in women infected with sextuple mutant parasites. Six trials of IPTp showed that neither amodiaquine, mefloquine, nor chloroquine-azithromycin are suitable replacements for sulfadoxine-pyrimethamine because of poor tolerability. Furthermore, four trials showed that intermittent screening and treatment with the current generation of malaria rapid diagnostic tests was not a suitable alternative strategy to IPTp with sulfadoxine-pyrimethamine, even in areas with high prevalence of quintuple mutations. Two trials showed that IPTp with dihydroartemisinin-piperaquine was well tolerated, effective, and acceptable for IPTp, with monthly regimens being the most effective. Coverage of IPTp and insecticide-treated nets continues to lag behind targets. The key barriers to uptake are well documented, and many are open to intervention. Outside of Africa, a single trial suggests a potential role for integrated approaches that combine sulfadoxine-pyrimethamine with azithromycin for IPTp in areas of Papua New Guinea where malaria transmission is high. Modelling analysis suggests the importance of the prevention of malaria early in pregnancy and the need to protect pregnant women declines more slowly than the rate at which transmission declines. Improved funding has led to an increase in the number of prevention trials in the past decade, showing the value of more sustained protection with monthly IPTp regimens. There is a need for confirmatory trials of the safety, efficacy, and feasibility of IPTp with dihydroartemisinin-piperaquine, for studies of intermittent screening and treatment with more sensitive rapid diagnostic tests, for studies of integrated strategies for malaria and other co-infections, and for studies of prevention strategies for malaria in pregnant women who are HIV-positive and living outside of Africa. Additional research is required on how to improve uptake of WHO's updated policy on IPTp with sulfadoxine-pyrimethamine and insecticide-treated nets.

Social and economic impacts of congenital Zika syndrome in Brazil: Study protocol and rationale for a mixed-methods study.

Global concern broke out in late 2015 as thousands of children in Brazil were born with microcephaly, which was quickly linked to congenital infection with Zika virus (ZIKV). ZIKV is now known to cause a wider spectrum of severe adverse outcomes-congenital Zika syndrome (CZS)-and also milder impairments. This study aimed to explore the social and economic impacts of CZS in Brazil. Data was collected through mixed methods across two settings: Recife City and Jaboatão dos Guararapes in Pernambuco State (the epicentre of the epidemic), and the city of Rio de Janeiro (where reports of ZIKV infection and CZS were less frequent). Data was collected May 2017-January 2018. Ethical standards were adhered to throughout the research. In-depth qualitative interviews were conducted with: mothers and other carers of children with CZS (approximately 30 per setting), pregnant women (10-12 per setting), men and women of child-bearing age (16-20 per setting), and health professionals (10-12 per setting). Thematic analysis was undertaken independently by researchers from at least two research settings, and these were shared for feedback. A case-control study was undertaken to quantitatively explore social and economic differences between caregivers of a child with CZS (cases) and caregivers with an unaffected child (controls). We aimed to recruit 100 cases and 100 controls per setting, from existing studies. The primary caregiver, usually the mother, was interviewed using a structured questionnaire to collect information on: depression, anxiety, stress, social support, family quality of life, health care and social service use, and costs incurred by families. Multivariable logistic regression analyses were used to compare outcomes for cases and controls. Costs incurred as a result of CZS were estimated from the perspective of the health system, families and society. Modelling was undertaken to estimate the total economic burden of CZS from those three perspectives.

Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts.

Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa: analysis and modelling of results from a non-inferiority trial.

BACKGROUND: Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment (ISTp) with artemether-lumefantrine (AL) as an alternative strategy to IPTp-SP was estimated followed by a simulation of the effects on cost-effectiveness of decreasing efficacy of IPTp-SP due to SP resistance. The analysis was based on results from a multi-centre, non-inferiority trial conducted in West Africa. METHODS: A decision tree model was analysed from a health provider perspective. Model parameters for all trial countries with appropriate ranges and distributions were used in a probabilistic sensitivity analysis. Simulations were performed in hypothetical cohorts of 1000 pregnant women who received either ISTp-AL or IPTp-SP. In addition a cost-consequences analysis was conducted. Trial estimates were used to calculate disability-adjusted-life-years (DALYs) for low birth weight and severe/moderate anaemia (both shown to be non-inferior for ISTp-AL) and clinical malaria (inferior for ISTp-AL). Cost estimates were obtained from observational studies, health facility costings and public procurement databases. Results were calculated as incremental cost per DALY averted. Finally, the cost-effectiveness changes with decreasing SP efficacy were explored by simulation. RESULTS: Relative to IPTp-SP, delivering ISTp-AL to 1000 pregnant women cost US$ 4966.25 more (95 % CI US$ 3703.53; 6376.83) and led to a small excess of 28.36 DALYs (95 % CI -75.78; 134.18), with LBW contributing 81.3 % of this difference. The incremental cost-effectiveness ratio was -175.12 (95 % CI -1166.29; 1267.71) US$/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp-AL becomes cost-effective depends on assumptions about the contribution of bed nets to malaria control, bed net coverage and the willingness-to-pay threshold used. CONCLUSIONS: At SP efficacy levels currently observed in the trial settings it would not be cost-effective to switch from IPTp-SP to ISTp-AL, mainly due to the substantially higher costs of ISTp-AL and limited difference in outcomes. The modelling results indicate thresholds below which IPT-SP efficacy must fall for ISTp-AL to become a cost-effective option for the prevention of malaria in pregnancy.

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic Area Where Plasmodium vivax Predominates.

BACKGROUND: Information on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon. METHODS/PRINCIPAL FINDINGS: Between January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax infection. CONCLUSION: Despite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may help health policy decisions for the current control and future elimination of malaria in the area.

Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy. METHODS: The cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women's loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken. RESULTS: For HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet. CONCLUSIONS: Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price. TRIALS REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440.

Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data.

BACKGROUND: In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). METHODS: For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. FINDINGS: The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV-negative women was $6·2 per DALY averted. INTERPRETATION: Our findings lend strong support to the WHO guidelines that recommend a monthly dose of IPTp-SP from the second trimester onwards. FUNDING: Malaria in Pregnancy Consortium and the Bill & Melinda Gates Foundation.