Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia.

BACKGROUND: A number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders. METHODS: Using an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective. RESULTS: Under a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination. CONCLUSIONS: Our study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations.

Cost-effectiveness of Increasing Access to Contraception during the Zika Virus Outbreak, Puerto Rico, 2016.

We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus-related costs by $65.2 million ($2.8 million from less Zika virus testing and monitoring and $62.3 million from avoided costs of Zika virus-associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs.

Cost projections for implementation of safety interventions to prevent transfusion-transmitted Zika virus infection in the United States.

BACKGROUND: In August 2016, the Food and Drug Administration advised US blood centers to screen all whole blood and apheresis donations for Zika virus (ZIKV) with an individual-donor nucleic acid test (ID-NAT) or to use approved pathogen reduction technology (PRT). The cost of implementing this guidance nationally has not been assessed. STUDY DESIGN AND METHODS: Scenarios were constructed to characterize approaches to ZIKV screening, including universal ID-NAT, risk-based seasonal allowance of minipool (MP) NAT by state, and universal MP-NAT. Data from the 2015 National Blood Collection and Utilization Survey (NBCUS) were used to characterize the number of donations nationally and by state. For each scenario, the estimated cost per donor ($3-$9 for MP-NAT, $7-$13 for ID-NAT) was multiplied by the estimated number of relevant donations from the NBCUS. Cost of PRT was calculated by multiplying the cost per unit ($50-$125) by the number of units approved for PRT. Prediction intervals for costs were generated using Monte Carlo simulation methods. RESULTS: Screening all donations in the 50 states and DC for ZIKV by ID-NAT would cost $137 million (95% confidence interval [CI], $109-$167) annually. Allowing seasonal MP-NAT in states with lower ZIKV risk could reduce NAT screening costs by 18% to 25%. Application of PRT to all platelet (PLT) and plasma units would cost $213 million (95% CI, $156-$304). CONCLUSION: Universal ID-NAT screening for ZIKV will cost US blood centers more than $100 million annually. The high cost of PRT for apheresis PLTs and plasma could be mitigated if, once validated, testing for transfusion transmissible pathogens could be eliminated.

Stagnant contraceptive sales after the Zika epidemic in Brazil.

OBJECTIVES: Our aim was to assess national hormonal and non-hormonal contraceptive sales in Brazil after the Zika virus outbreak. METHODS: Pharmaceutical companies based in Brazil provided data on monthly sales from September 2016 to June 2017. Data from both the public and private sectors were obtained about sales of registered, available modern contraceptive methods: combined oral contraceptive pill; progestin-only pill; vaginal and transdermal contraceptives; injectable contraceptives; long-acting reversible contraceptive (LARC) methods, including the copper-releasing intrauterine device, the levonorgestrel-releasing intrauterine system and the etonogestrel-releasing subdermal implant; and emergency contraceptive pills. RESULTS: Seventy-eight percent of sales comprised pills, patches and vaginal rings (11.1-13.8 million cycles/units per month), followed by emergency contraceptive pills (1.8-2.6 million pills), injectables (1.2-1.4 million ampoules) and LARC methods (6500-17,000 devices). CONCLUSIONS: The data showed much higher sales of short-acting methods compared with more effective LARC methods. The public sector needs to strengthen its focus on ensuring better access to LARC methods through a systematic approach ensuring regular supply, improved professional skills and better demand generation to couples wishing to avoid or delay pregnancy. In Zika virus-affected areas, many women of reproductive age may want to delay or postpone pregnancy by using an effective LARC method. The public sector should review its policies on LARC, as the need for these methods especially in Zika virus endemic areas may increase. A clear emphasis on quality in services, access and use is warranted.

Short-term economic impact of the Zika virus outbreak.

Zika virus (ZIKV) is mainly transmitted by mosquitoes bites. However, transmission by sexual contacts has been reported in 11 non endemic countries. The rapid spread of ZIKV in Latin American and Caribbean Countries (LCR), person-to-person transmission and perceived risk on people's well being can affect the emerging economies of LCR which historically dependent on truism. Here we present an analysis on economic outputs for assessing the current impact of ZIKV on markets. Our analysis show an unexpected resilience of LCR markets to international alerts. This positive response represents an opportunity to scale-up interventions for preventing the further spreading of the ZIKV epidemic.

Socioeconomic disparities associated with symptomatic Zika virus infections in pregnancy and congenital microcephaly: A spatiotemporal analysis from Goiânia, Brazil (2016 to 2020).

The Zika virus (ZIKV) epidemic, which was followed by an unprecedented outbreak of congenital microcephaly, emerged in Brazil unevenly, with apparent pockets of susceptibility. The present study aimed to detect high-risk areas for ZIKV infection and microcephaly in Goiania, a large city of 1.5 million inhabitants in Central-West Brazil. Using geocoded surveillance data from the Brazilian Information System for Notifiable Diseases (SINAN) and from the Public Health Event Registry (RESP-microcefalia), we analyzed the spatiotemporal distribution and socioeconomic indicators of laboratory confirmed (RT-PCR and/or anti-ZIKV IgM ELISA) symptomatic ZIKV infections among pregnant women and clinically confirmed microcephaly in neonates, from 2016 to 2020. We investigated temporal patterns by estimating the risk of symptomatic maternal ZIKV infections and microcephaly per 1000 live births per month. We examined the spatial distribution of maternal ZIKV infections and microcephaly cases across the 63 subdistricts of Goiania by manually plotting the geographical coordinates. We used spatial scan statistics estimated by discrete Poisson models to detect high clusters of maternal ZIKV infection and microcephaly and compared the distributions by socioeconomic indicators measured at the subdistrict level. In total, 382 lab-confirmed cases of maternal ZIKV infections, and 31 cases of microcephaly were registered in the city of Goiania. More than 90% of maternal cases were reported between 2016 and 2017. The highest incidence of ZIKV cases among pregnant women occurred between February and April 2016. A similar pattern was observed in the following year, although with a lower number of cases, indicating seasonality for ZIKV infection, during the local rainy season. Most congenital microcephaly cases occurred with a time-lag of 6 to 7 months after the peak of maternal ZIKV infection. The highest estimated incidence of maternal ZIKV infections and microcephaly were 39.3 and 2.5 cases per 1000 livebirths, respectively. Districts with better socioeconomic indicators and with higher proportions of self-identified white inhabitants were associated with lower risks of maternal ZIKV infection. Overall, the findings indicate heterogeneity in the spatiotemporal patterns of maternal ZIKV infections and microcephaly, which were correlated with seasonality and included a high-risk geographic cluster. Our findings identified geographically and socio-economically underprivileged groups that would benefit from targeted interventions to reduce exposure to vector-borne infections.

A systematic examination of international funding flows for Ebola virus and Zika virus outbreaks 2014-2019: donors, recipients and funding purposes.

INTRODUCTION: There has been no systematic comparison of how the policy response to past infectious disease outbreaks and epidemics was funded. This study aims to collate and analyse funding for the Ebola epidemic and Zika outbreak between 2014 and 2019 in order to understand the shortcomings in funding reporting and suggest improvements. METHODS: Data were collected via a literature review and analysis of financial reporting databases, including both amounts donated and received. Funding information from three financial databases was analysed: Institute of Health Metrics and Evaluation's Development Assistance for Health database, the Georgetown Infectious Disease Atlas and the United Nations Financial Tracking Service. A systematic literature search strategy was devised and applied to seven databases: MEDLINE, EMBASE, HMIC, Global Health, Scopus, Web of Science and EconLit. Funding information was extracted from articles meeting the eligibility criteria and measures were taken to avoid double counting. Funding was collated, then amounts and purposes were compared within, and between, data sources. RESULTS: Large differences between funding reported by different data sources, and variations in format and methodology, made it difficult to arrive at precise estimates of funding amounts and purpose. Total disbursements reported by the databases ranged from $2.5 to $3.2 billion for Ebola and $150-$180 million for Zika. Total funding reported in the literature is greater than reported in databases, suggesting that databases may either miss funding, or that literature sources overreport. Databases and literature disagreed on the main purpose of funding for socioeconomic recovery versus outbreak response. One of the few consistent findings across data sources and diseases is that the USA was the largest donor. CONCLUSION: Implementation of several recommendations would enable more effective mapping and deployment of outbreak funding for response activities relating to COVID-19 and future epidemics.

Social determinants associated with Zika virus infection in pregnant women.

This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015-2016 epidemic in Salvador, Brazil. METHODS: We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status. RESULTS: We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04-1.35) and food insecurity (aPR 1.17; 95%CI 1.01-1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97-0.998). CONCLUSION: Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population.

Climatic and socio-economic factors supporting the co-circulation of dengue, Zika and chikungunya in three different ecosystems in Colombia.

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.

[Family dynamics of children with congenital Zika syndrome in Petrolina, Pernambuco State, Brazil]. / Dinâmica familiar de criança com a síndrome congênita do Zika vírus no Município de Petrolina, Pernambuco, Brasil.

Brazil witnessed a significant increase in the number of cases of microcephaly in infants born in the second semester of 2015. There were 162 cases in 2014, increasing to 1,608 in 2015. The condition is associated with impairments in various bodily functions, leading to limitations in infant development. This study aims to analyze the family dynamics of children with congenital Zika syndrome (CZS) in Petrolina, Pernambuco State. Data collection used consultation in patient charts and interviews with parents using a semi-structured script. A qualitative/quantitative approach was used, including all of the mothers and other family members accompanying children with CZS at the referral unit, the Amália Granja Alencar Clinic. Discourse analysis applied the content analysis technique. The results in the category "changes in daily living" for families of children with CZS were grouped into three subcategories: activities of daily living (ADL), financial and occupational impacts associated with the CZS diagnosis, and changes in the marital relationship after the diagnosis. The study showed that care for the child with CZS is mostly concentrated in women in the family, and that the diagnosis leads to significant changes in the family dynamics, with the child's extensive dependence on the caregiver, increasing expenses, and work absenteeism.

No Brasil, houve aumento no número de casos de microcefalia detectados em crianças nascidas no segundo semestre de 2015. Esses casos tiveram incremento significativo no país. Em 2014, foram 162 ocorrências, aumentando, em 2015, para 1.608. Essa condição está associada a vários acometimentos nas funções do organismo, levando a limitações no desenvolvimento infantil. Esta pesquisa objetiva analisar a dinâmica familiar de criança com a síndrome congênita associada ao Zika vírus (SCZV) no Município de Petrolina, Pernambuco. Como instrumento de coleta, utilizou-se a consulta ao prontuário e a realização de entrevista por meio de roteiro semiestruturado. Empregou-se abordagem quali-quantitativa, envolvendo a totalidade das mães e dos familiares que acompanhavam as crianças com a SCZV na unidade de saúde de referência, AME Amália Granja Alencar. Na análise dos discursos, aplicou-se a técnica de análise de conteúdo. Os resultados relacionados à categoria mudanças da vida diária de familiares de criança com a SCZV foram agrupados em três subcategorias: atividade da vida diária (AVD); impactos financeiros e no trabalho associados à descoberta da SCZV; e mudança na relação conjugal após a descoberta da SCZV. A pesquisa demonstrou majoritariamente que o cuidado da criança com SCZV está centrado na figura feminina e que o diagnóstico traz significativas mudanças na dinâmica familiar, como maior dependência da criança ao cuidador, aumento de gastos financeiros e absenteísmo no trabalho.

En Brasil, se produjo un aumento en el número de casos de microcefalia detectada en niños nacidos en el segundo semestre de 2015. Estos casos sufrieron un incremento significativo en el país. En 2014, fueron 162 incidencias, aumentando, en 2015, hasta 1.608. Esta enfermedad está asociada con varias alteraciones en las funciones del organismo, provocando limitaciones en el desarrollo infantil. El objetivo de esta investigación fue analizar la dinámica familiar de niños con el síndrome congénito asociado al virus Zika (SCZ) en el municipio de Petrolina, Pernambuco. Como instrumento de recogida, se realizaron consultas del historial clínico, así como una entrevista semiestructurada. Se empleó un abordaje cuali-cuantitativo, implicando a la totalidad de las madres y de los familiares que acompañaban a los niños con el SCZ en la unidad de salud de referencia, AME Amália Granja Alencar. En el análisis de los discursos se aplicó la técnica de análisis de contenido. Los resultados relacionados con la categoría cambios de la vida diaria de familiares del niño con el SCZ se agruparon en tres subcategorías: actividad de la vida diaria (AVD), impactos financieros y en el trabajo asociados al descubrimiento del SCZ y cambios en la relación conyugal tras el descubrimiento del SCZ. La investigación demostró que mayoritariamente el cuidado del niño con SCZ está centrado en la figura femenina, y que el diagnóstico conlleva significativos cambios en la dinámica familiar, como una mayor dependencia del niño del cuidador, aumento de gastos financieros y absentismo en el trabajo.

The Potential Economic Value of a Zika Vaccine for a Woman of Childbearing Age.

INTRODUCTION: With Zika vaccine candidates under development and women of childbearing age being the primary target population, now is the time to map the vaccine (e.g., efficacy and duration of protection) and vaccination (e.g., cost) characteristic thresholds at which vaccination becomes cost effective, highly cost effective, and cost saving. METHODS: A Markov model was developed (to represent 2019 circumstances, US$ and INT$, Region of the Americas) to simulate a woman of childbearing age and the potential risk and clinical course of a Zika infection. RESULTS: Compared with no vaccination, vaccination was cost effective (incremental cost-effectiveness ratio: US$1,254-$82,900/disability-adjusted life years averted) when the risk of infection was ≥0.05%-0.08% (varying with country income), vaccine efficacy was ≥25%, and vaccination cost was US$1-$7,500 (INT$5-$10,000 depending on country income level). Vaccination was dominant (i.e., saved costs and provided beneficial health effects) when the infection risk was ≥0.1% for a vaccine efficacy ≥75% and when the infection risk was ≥0.5% for a vaccine efficacy ≥25%, for scenarios where vaccination conferred a 1-year duration of protection and cost ≤$200. In some cases, the vaccine was cost effective when the risk was as low as 0.015%, the cost was as high as $7,500 (INT$10,000), the efficacy was as low as 25%, and the duration of protection was 1 year. CONCLUSIONS: The thresholds at which vaccination becomes cost effective and cost saving can provide targets for Zika vaccine development and implementation.

An investigation into the knowledge, perceptions and role of personal protective technologies in Zika prevention in Colombia.

BACKGROUND: Arboviruses transmitted by day-biting Aedes mosquitoes are a major public health concern. With the challenges inherent in arbovirus vaccine and therapeutics development, vector control and bite prevention strategies are among the limited options available for immediate intervention. Bite prevention through personal protective technologies (PPT), such as topical mosquito repellents or repellent-impregnated clothing, may help to decrease biting rates and, therefore, the risk of disease in groups most susceptible to adverse outcomes from Zika virus. However, achieving high uptake and compliance with PPT can be challenging. METHODOLOGY/PRINCIPAL FINDINGS: To gain an insight into the knowledge and concerns of pregnant women surrounding Zika and their opinions regarding PPT, particularly repellent clothing, a focus group study was carried out with pregnant women, women of reproductive age, and semi-structured interviews with their male partners in two cities in Colombia. The discussions revealed shortfalls in basic knowledge of Zika virus, with several pregnant participants reporting being unaware of the potential for Zika-related congenital malformations. Although participants generally considered Zika to be a significant personal threat, most rated it as less of a concern than dengue or diarrheal diseases. Overall, repellent clothing and other forms of PPT were viewed as effective, although some participants expressed concerns over the high costs of repellents, and safety fears of regular contact with repellent chemicals, which they perceived as potentially harmful. Plant-derived repellents were considered to be safer than synthetic chemical repellents. Discussions also highlighted that health centers were the preferred source of information on bite-reduction. CONCLUSIONS/SIGNIFICANCE: Achieving high uptake and compliance with PPT in populations most at risk of adverse outcomes from Zika infection requires engaging key users in open dialogue to identify and address any practical issues regarding PPT use, and concerns over safety. The findings presented here suggest that educational campaigns should strongly emphasize the risks associated with Zika during pregnancy, and discuss safety profiles of approved synthetic repellents and the availability of EPA-approved plant-based repellents. In addition, the economic and political context should be a major consideration when evaluating personal mosquito-repellent strategies.