Eastern Mediterranean Health Journal [2024; Vol.30, Issue 1] / [المجلة الصحية لشرق المتوسط [2024; المجلد 30 , العدد 1

Eastern Mediterranean Health Journal is the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas concepts epidemiological data research findings and other information with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession medical and other health educational institutes interested NGOs WHO Collaborating Centres and individuals within and outside the Region.

المجلة الصحية لشرق المتوسط هى المجلة الرسمية التى تصدرعن المكتب الاقليمى لشرق المتوسط بمنظمة الصحة العالمية. وهى منبر لتقديم السياسات والمبادرات الجديدة فى الصحة العامة والخدمات الصحية والترويج لها، و لتبادل الاراء و المفاهيم والمعطيات الوبائية ونتائج الابحاث وغير ذلك من المعلومات، و خاصة ما يتعلق منها باقليم شرق المتوسط. وهى موجهة الى كل اعضاء المهن الصحية، والكليات الطبية وسائر المعاهد التعليمية، و كذا المنظمات غير الحكومية المعنية، والمراكز المتعاونة مع منظمة الصحة العالمية والافراد المهتمين بالصحة فى الاقليم و خارجه

La Revue de Santé de la Méditerranée Orientale est une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine de la santé publique et des services de santé ainsi qu’à l’échange d’idées de concepts de données épidémiologiques de résultats de recherches et d’autres informations se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé aux membres des instituts médicaux et autres instituts de formation médico-sanitaire aux ONG Centres collaborateurs de l’OMS et personnes concernés au sein et hors de la Région.

Advancing Chikungunya Diagnosis: A Cost-Effective and Rapid Visual employing Loop-mediated isothermal reaction.

The diagnosis of Chikungunya (CHIKV), along with the simultaneous monitoring of virus circulation in the population or vectors, is essential for global health. Although effective diagnostic methods for CHIKV, such as RT-qPCR, exist, their utilization is constrained by high costs. With the aim of contributing to the field of diagnostics, we have developed a diagnostic assay using isothermal amplification technology with visually interpretable results. This test can detect the virus within a maximum timeframe of 30 minutes. The detection limit of RT-LAMP CHIKV was found to be 66 copies of RNA molecules (Ct ≅ 31.28), and no cross-reactivity with other arboviruses was observed. During test validation, our assay demonstrated a sensitivity of 80.43%, specificity of 100%, and an overall accuracy of 88.89%. By utilizing more cost-effective reagents and equipment compared to RT-qPCR, this test holds the potential for broader application and enhanced accessibility, particularly in point-of-care settings.

Entomological risk assessment for transmission of arboviral diseases by Aedes mosquitoes in a domestic and forest site in Accra, Ghana.

Dengue, Zika and chikungunya are Aedes-borne viral diseases that have become great global health concerns in the past years. Several countries in Africa have reported outbreaks of these diseases and despite Ghana sharing borders with some of these countries, such outbreaks are yet to be detected. Viral RNA and antibodies against dengue serotype-2 have recently been reported among individuals in some localities in the regional capital of Ghana. This is an indication of a possible silent transmission ongoing in the population. This study, therefore, investigated the entomological transmission risk of dengue, Zika and chikungunya viruses in a forest and domestic population in the Greater Accra Region, Ghana. All stages of the Aedes mosquito (egg, larvae, pupae and adults) were collected around homes and in the forest area for estimation of risk indices. All eggs were hatched and reared to larvae or adults for morphological identification together with larvae and adults collected from the field. The forest population had higher species richness with 7 Aedes species. The predominant species of Aedes mosquitoes identified from both sites was Aedes aegypti (98%). Aedes albopictus, an important arbovirus vector, was identified only in the peri-domestic population at a prevalence of 1.5%, significantly higher than previously reported. All risk indices were above the WHO threshold except the House Index for the domestic site which was moderate (19.8). The forest population recorded higher Positive Ovitrap (34.2% vs 26.6%) and Container (67.9% vs 36.8%) Indices than the peri-domestic population. Although none of the mosquito pools showed the presence of dengue, chikungunya or Zika viruses, all entomological risk indicators showed that both sites had a high potential arboviral disease transmission risk should any of these viruses be introduced. Continuous surveillance is recommended in these and other sites in the Metropolis to properly map transmission risk areas to inform outbreak preparedness strategies.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

[Evaluation of technological development in health from the occurrence of the zika and chikungunya epidemics in Brazil]. / Avaliação do desenvolvimento tecnológico em saúde a partir da ocorrência das epidemias de zika e chikungunya no Brasil.

This study aims to understand how the zika and chikungunya epidemics incited technological development. We surveyed epidemiological data and technological prospecting, using data from Brazilian National Institute of Industry Property (INPI) and Orbit Intelligence, and analyzed products developed/under development worldwide and products registered in Brazil by Brazilian Health Regulatory Agency (Anvisa). In 2016, the highest number of total cases was observed for both diseases. Brazil's technological prospection revealed the existence of a global interest in developing technologies for these diseases and filing their patents in Brazil, with companies as the main depositors. Global technological prospecting showed that 2016 is an important milestone in the evolution of the number of patents for zika and chikungunya, suggesting that Brazilian epidemics stimulated the world in the development of new health inputs. The United States and China are the main jurisdictions, with universities as the largest depositors. Global product analysis revealed that only two products reached the market for zika and one for chikungunya, and vaccines are in the top category. A research in Anvisa revealed more products registered for zika compared to chikungunya. The main legal manufacturers are Brazilian companies, with DiaSorin S.p.A., Eco Diagnóstica Ltda., and Chembio Diagnostics Brazil Ltda. leading the registration requests. Despite the visible stimulus to research, development, and patenting generated by the zika and chikungunya epidemics in Brazil, such stimulus did not guarantee the arrival of new products on the market and population access to these products.

Buscando compreender como as epidemias de zika e chikungunya incitaram o desenvolvimento tecnológico, este estudo realizou levantamento de dados epidemiológicos e prospecção tecnológica, utilizando dados do Instituto Nacional da Propriedade Industrial (INPI) e do Orbit Intelligence. Ainda, analisou produtos desenvolvidos e em desenvolvimento a nível mundial e aqueles registrados no Brasil por meio da Agência Nacional de Vigilância Sanitária (Anvisa). No ano de 2016, observou-se o maior número de casos totais para ambas as doenças. A prospecção tecnológica nacional revelou que há interesse global em desenvolver tecnologias para essas doenças e depositar suas patentes no Brasil, tendo as empresas como principais depositantes. Por sua vez, a prospecção tecnológica global mostrou que o ano de 2016 configura-se como importante marco na evolução do número de patentes para zika e chikungunya, sugerindo que as epidemias brasileiras estimularam o mundo no desenvolvimento de novos insumos para a saúde. Os Estados Unidos e a China são as principais jurisdições, tendo as universidades como maiores depositantes. A análise de produtos a nível global revelou que apenas dois chegaram ao mercado para zika e um para chikungunya, e as vacinas estão na categoria principal. A busca na Anvisa revelou que há mais produtos registrados para zika do que em comparação à chikungunya. Os principais fabricantes legais são empresas brasileiras, com pedidos de registro realizados principalmente pelas empresas DiaSorin S.p.A., ECO Diagnóstica Ltda. e Chembio Diagnostics Brazil Ltda. Apesar do visível estímulo à pesquisa, desenvolvimento e patenteamento gerado pelas epidemias de zika e chikungunya no Brasil, isso não garantiu a chegada de novos produtos ao mercado nem acesso da população a eles.

Con el fin de comprender cómo las epidemias de zika y chikunguña estimularon el desarrollo tecnológico, este estudio realizó la recopilación de datos epidemiológicos y la prospección tecnológica, utilizando datos del Instituto Nacional de la Propiedad Industrial (INPI) y Orbit Intelligence, y analizó los productos desarrollados y en desarrollo en todo el mundo y productos registrados en Brasil por la Agencia Nacional de Vigilancia Sanitaria (Anvisa). En 2016 se observó el mayor número de casos para ambas enfermedades. La prospección tecnológica nacional reveló que existe un interés mundial por desarrollar tecnologías para estas enfermedades y depositar sus patentes en Brasil, con las empresas como los principales depositantes. La prospección tecnológica mundial mostró que 2016 fue un hito importante en la evolución del número de patentes de zika y chikunguña, lo que sugiere que las epidemias brasileñas estimularon el desarrollo mundial de nuevos insumos para la salud. EE.UU. y China son las principales jurisdicciones, con las universidades como las mayores depositantes. El análisis global de productos reveló que solo 2 han llegado al mercado para zika y 1 para chikunguña, y las vacunas están en la categoría superior. La búsqueda en Anvisa reveló la existencia de más productos registrados para zika que para chikunguña. Los principales fabricantes legales son empresas brasileñas, con las solicitudes de registro realizadas principalmente por DiaSorin S.p.A., Eco Diagnóstica Ltda. y Chembio Diagnostics Brazil Ltda. Aunque hubo una notable promoción a la investigación, desarrollo y patentamiento generado por las epidemias de zika y chikunguña en Brasil, esto no implicó la llegada de nuevos productos al mercado y el acceso a ellos por parte de la población.

The Development and Evaluation of a Combined Infection-Rheumatology Assessment Service in Response to the Chikungunya Fever Epidemic.

The chikungunya virus is an arthritogenic alphavirus. Acute infection may be followed by persistent arthralgia, often causing significant functional impairment. The 2014-2015 chikungunya fever (CHIKF) epidemic resulted in a marked increase in cases presenting to rheumatology and tropical diseases services. A combined multidisciplinary rheumatology-tropical diseases service for assessment, management, and follow-up of patients with proven CHIKF and persistent (≥ 4 weeks) arthralgia was proposed and rapidly developed at The Hospital for Tropical Diseases in London. Rapid set up of a multidisciplinary clinic in response to the epidemic was achieved. Of a total of 54 patients, 21 (38.9%) patients with CHIKF developed persistent arthralgia and were reviewed by the multidisciplinary service. A combined assessment approach enabled comprehensive multidisciplinary assessment of CHIKF, assessment of joint pathology through ultrasound, and appropriate follow-up. A combined rheumatology-tropical diseases service was successfully used to identify and assess CHIKF-associated morbidity. Future outbreaks may be approached by establishing tailored multidisciplinary clinics.

Perfil das notificações de dengue e febre chikungunya em Cabo Frio/Rj, 2014-2019 / Profile of dengue and chikungunya notifications in Cabo Frio/Rj, 2014-2019 / Perfil de las notificaciones de dengue y chikungunya en Cabo Frio/Rj, 2014-2019

Introdução: De acordo com a literatura científica, diagnósticos clínicos diferenciais de arboviroses representam uma dificuldade no que tange à dengue, na medida em que está no Brasil há muitos anos, o que acarreta em ser a arbovirose mais conhecida no país. As notificações de arboviroses se tornaram obrigatórias para inserção no SINAN, possibilitando a construção de perfis demográficos e o cálculo de incidências a partir de informações específicas para estas doenças. No que tange à dengue, a epidemia deste agravo ocorre no país desde 1986, evidenciando falhas na prevenção, relacionadas a aspectos socioeconômicos e ambientais. Objetivo: analisar perfis das notificações de dengue e febre de chikungunya dos casos notificados no município de Cabo Frio. Metodologia: Trata-se de estudo transversal e descritivo, com uso de dados secundários do SINAN referentes a casos de arboviroses no município de Cabo Frio/RJ. Foram observadas variáveis relacionadas ao sexo, escolaridade, raça/cor e critérios de confirmação, além do grau de completude. Resultados: Foram notificados 8.777 casos suspeitos de arboviroses, incluindo-se 1.367 notificações (15,57%) referentes à febre de chikungunya e 1.986 (22,63%), à dengue. Em relação ao desfecho, 1186 casos (51,45%) foram fechados como inconclusivos e 344 destes (14,92%) foram descartados como arboviroses. Dentre os inconclusivos, 943 (79,51%) eram referentes à notificação de dengue, idem para os 277 casos descartados (80,52%). Conclusão: Observou-se baixa taxa de completude nas fichas de notificação, explicada pelo baixo número de recursos humanos e pela insuficiente infraestrutura. Sugere-se a interação de diferentes profissionais e pesquisadores, facilitando a compreensão da complexa dinâmica das arboviroses em questão.

Introduction: According to the scientific literature, differential clinical diagnoses of arboviruses represent a difficulty with regard to dengue, as it has been present in Brazil for many years, which makes it the most well-known arbovirus in the country. Notifications of arboviruses became mandatory for inclusion in SINAN, enabling the construction of demographic profiles and the calculation of incidences based on specific information for these diseases. With regard to dengue, the epidemic of this disease has occurred in the country since 1986, showing failures in prevention, related to socioeconomic and environmental aspects. Objective: to analyze profiles of notifications of dengue and chikungunya fever of cases notified in the municipality of Cabo Frio. Methodology: This is a cross-sectional and descriptive study, using secondary data from SINAN regarding cases of arboviruses in the municipality of Cabo Frio/RJ. Variables related to sex, education, race/color and confirmation criteria were observed, in addition to the degree of completeness. Results: 8,777 suspected cases of arboviruses were reported, including 1,367 reports (15.57%) referring to chikungunya fever and 1,986 (22.63%) to dengue fever. Regarding the outcome, 1186 cases (51.45%) were closed as inconclusive and 344 of these (14.92%) were discarded as arboviruses. Among the inconclusive ones, 943 (79.51%) were related to dengue notification, the same for the 277 discarded cases (80.52%). Conclusion: A low completeness rate was observed in the notification forms, explained by the low number of human resources and insufficient infrastructure. It is suggested the interaction of different professionals and researchers, facilitating the understanding of the complex dynamics of the arboviruses in question.

Introducción: Según la literatura científica, los diagnósticos clínicos diferenciales de los arbovirus representan una dificultad con respecto al dengue, ya que está presente en Brasil desde hace muchos años, lo que lo convierte en el arbovirus más conocido en el país. Las notificaciones de arbovirus pasaron a ser obligatorias para su inclusión en el SINAN, lo que permitió la construcción de perfiles demográficos y el cálculo de incidencias a partir de información específica de estas enfermedades. Con respecto al dengue, la epidemia de esta enfermedad se presenta en el país desde 1986, mostrando fallas en la prevención, relacionadas con aspectos socioeconómicos y ambientales. Objetivo: analizar perfiles de notificaciones de dengue y fiebre chikungunya de los casos notificados en el municipio de Cabo Frio. Metodología: Se trata de un estudio transversal y descriptivo, utilizando datos secundarios del SINAN sobre casos de arbovirus en el municipio de Cabo Frio/RJ. Se observaron variables relacionadas con el sexo, escolaridad, raza/color y criterios de confirmación, además del grado de completitud. Resultados: se notificaron 8.777 casos sospechosos de arbovirus, de los cuales 1.367 (15,57%) se referían a fiebre chikungunya y 1.986 (22,63%) a dengue. En cuanto al resultado, 1186 casos (51,45%) se cerraron como no concluyentes y 344 de estos (14,92%) se descartaron como arbovirus. Entre los inconclusos, 943 (79,51%) estaban relacionados con la notificación de dengue, lo mismo para los 277 casos descartados (80,52%). Conclusión: Se observó un bajo índice de completitud en los formularios de notificación, explicado por el bajo número de recursos humanos y la infraestructura insuficiente. Se sugiere la interacción de diferentes profesionales e investigadores, facilitando la comprensión de la compleja dinámica de los arbovirus en cuestión.

Assessment of Dengue and Chikungunya Infections among Febrile Patients Visiting Four Healthcare Centres in Yaoundé and Dizangué, Cameroon.

Dengue and chikungunya are now widely distributed in Cameroon, but there is still not enough information on their prevalence in different epidemiological settings. This study was undertaken to assess the prevalence of dengue and chikungunya in both urban and rural settings in Cameroon using three diagnostic tools. From December 2019 to September 2021, willing febrile (temperature >38 °C) outpatients visiting four healthcare facilities in the cities of Yaoundé and Dizangué were screened for dengue, and chikungunya. Clinical features of patient were recorded in a form, and their blood samples were analysed using real-time reverse transcriptase-polymerase chain reaction (rtRT-PCR), rapid diagnostic tests (RDTs) and enzyme-linked immuno-sorbent assays (ELISA). Odds ratios were used to determine the level of association between socio-demographic factors, clinical features, and infection status. The Kappa coefficient permitted to assess the level of agreement between RDTs and ELISA. Overall, 301 febrile patients were recruited in the study: 198 in Yaoundé and 103 in Dizangué. The prevalence of infection varied with the diagnostic tool used. For dengue diagnostics, 110 patients were positive to rtRT-PCR: 90 (45.45%) in Yaoundé, and 20 (19.42%) in Dizangué. The prevalence of dengue IgM using ELISA varied from 22.3% in Dizangué to 30.8% in Yaoundé. Dengue IgM rate using RDTs was 7.6% in Yaoundé and 3.9% in Dizangué. For chikungunya, one (0.5%) patient (Yaoundé, suburb) was positive to rtRT-PCR. The prevalence of chikungunya IgM according to ELISA varied from 18.4% in Dizangué to 21.7% in Yaoundé, while it was 4.5% in Yaoundé and 12.6% in Dizangué with RDTs. Only abdominal and retro-orbital pains were significantly associated with acute dengue infection. All four dengue serotypes were recorded, with a predominance of DENV-3 (35.45%) and DENV-4 (25.45%). Rapid Diagnostic Tests for either chikungunya or dengue displayed very poor sensitivity. This study further confirms the high endemicity of both dengue and chikungunya in Yaoundé and Dizangué. These data stress the need for active surveillance and the implementation of vector control measures to prevent the occurrence of outbreaks across the country.

Chikungunya in Brazil: An epidemic of high cost for private healthcare, 2017.

OBJECTIVE: We evaluated the impact of direct and indirect medical costs incurred through chikungunya infections in patients treated in Fortaleza, Brazil. METHODS: Cross-sectional study about the cost of illness. The valuation method of medical costs was based on the micro-costing approach (bottom-up). The study was carried out in a large general hospital of the private health network. The study population consisted of patients treated as suspected cases of chikungunya and hospital professionals who applied for sick leave due to chikungunya. RESULTS: In 2017, there were 2683 patients treated at this hospital who incurred an estimated cost of $383,514.40. From this amount, $174,322.91 (45.5%) were expended on emergency care, $194,700.59 (50.8%) on hospitalisations. 123 hospital professionals were infected with chikungunya and sick leave duration ranged between 1 and 19 days. Health professionals generated 746 days of absence and an amount of $14,490.90 due to absenteeism from work related to chikungunya. 31 symptoms were reported, especially arthralgia (91.1%) and fever (79.4%). There was a predominance of females (58.8%) and the age group of 20-39 years (42.1%). CONCLUSION: The average cost of admissions was over $2400. Considering the epidemic potential of chikungunya, our data indicate the huge economic burden of this disease to healthcare units in the presence of epidemics. Economic factors, added to the loss of life and the consequences of chronic chikungunya, make this disease a real scourge for countries with fewer material resources.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for an inactivated viral vaccine against Chikungunya virus.

Inactivated viral vaccines have long been used in humans for diseases of global health threat (e.g., poliomyelitis and pandemic and seasonal influenza) and the technology of inactivation has more recently been used for emerging diseases such as West Nile, Chikungunya, Ross River, SARS and especially for COVID-19. The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit and risk of several vaccine platform technologies, including inactivated viral vaccines. This paper uses the BRAVATO inactivated virus vaccine template to review the features of an inactivated whole chikungunya virus (CHIKV) vaccine that has been evaluated in several preclinical studies and clinical trials. The inactivated whole CHIKV vaccine was cultured on Vero cells and inactivated by ß-propiolactone. This provides an effective, flexible system for high-yield manufacturing. The inactivated whole CHIKV vaccine has favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the current inactivated whole CHIKV vaccine safety database with unblinded data from the ongoing studies: 850 participants from phase II study (parts A and B) outside of India, and 600 participants from ongoing phase II study in India, and completed phase I clinical studies for 60 subjects. Overall, the inactivated whole CHIKV vaccine has been well tolerated, with no significant safety issues identified. Evaluation of the inactivated whole CHIKV vaccine is continuing, with 1410 participants vaccinated as of 20 April 2022. Extensive evaluation of immunogenicity in humans shows strong, durable humoral immune responses.

A metapopulation approach to identify targets for Wolbachia-based dengue control.

Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.

Decomposition of socioeconomic inequalities in arboviral diseases in Brazil and Colombia (2007-2017).

BACKGROUND: We used surveillance data from Brazil and Colombia during 2007-2017 to assess the presence of socioeconomic inequalities on dengue, chikungunya and Zika at the neighborhood level in two Latin American cities. METHODS: To quantify the inequality, we estimated and decomposed the relative concentration index of inequality (RCI) accounting for the spatiotemporal distribution of the diseases. RESULTS: There were 281 426 arboviral cases notified in Fortaleza, Brazil, and 40 889 in Medellin, Colombia. The RCI indicated greater concentration of dengue cases among people living in low socioeconomic settings in both sites. The RCIs for chikungunya in Fortaleza covered the line of equality during their introduction in 2014, while the RCIs for Zika and chikungunya in Medellin indicated the presence of a small inequality. The RCI decomposition showed that year of notification and age were the main contributors to this inequality. In Medellin, the RCI decomposition showed that age and access to waste management accounted for 75.5%, 72.2% and 54.5% of the overall inequality towards the poor for dengue, chikungunya and Zika, respectively. CONCLUSIONS: Our study presents estimates of the socioeconomic inequality of arboviruses and its decomposition in two Latin American cities. We corroborate the concentration of arboviral diseases in low socioeconomic neighborhoods and identify that year of occurrence, age, presence of healthcare facilities and waste management are key determinants of the heterogenous distribution of endemic arboviruses across the socioeconomic spectrum.

Epidemiological burden of Chikungunya fever in Brazil, 2016 and 2017.

OBJECTIVES: To describe Chikungunya fever (CHIKF) cases and estimate the burden of the disease in Brazil between 2016 and 2017. METHODS: The first stage of this study consisted of a descriptive epidemiological study with estimations of incidence, mortality and case-fatality rates for each Brazilian state. The second stage provided estimates of the disease burden using DALY, an indicator that aggregates measures of morbidity (years lived with disability - YLD) and mortality (years of life lost - YLL) into a single value. RESULTS: In Brazil, the incidence rate in 2016 was 114.70 per 100,000 inhabitants, while the mortality rate was 0.15 per 100,000, for a case-fatality rate of 0.13%. In 2017, these figures were 87.59 and 0.12 per 100,000 inhabitants and 0.14%, respectively. The estimated CHIKF burden for Brazil in 2016 was 77,422.61 DALY or 0.3757 per 1000 inhabitants. In 2016, the YLL share of DALY was 10.04%, with YLD accounting for the remaining 89.96%. In 2017, the estimated burden was 59,307.59 DALY or 0.2856 per 1000 inhabitants, with YLL accounting for 9.65% of the total and YLD for 90.35%. CONCLUSION: CHIKF causes a significant disease burden in Brazil. The chronic phase of CHIKF is responsible for the largest portion of DALY. Deaths from CHIKF are a significant component of the disease burden, with YLL accounting for approximately 10% of the total DALY value.

Percepção da comunidade sobre suas ações preventivas contra dengue, zika e chikungunya nas cinco regiões do Brasil / Community perception of its preventive actions against dengue, zika and chikungunya in five Brazilian regions

Resumo O controle ambiental do vetor no interior e ao redor dos domicílios, enquanto estratégia fundamental para a prevenção de arboviroses como dengue, zika e chikungunya, demanda um envolvimento ininterrupto da população. A pandemia de Covid-19 e, consequentemente, o isolamento social necessário ao seu controle, têm reduzido a vigilância profissional nos domicílios, tornando a atuação da população ainda mais necessária. Estudos que buscam compreender o envolvimento das comunidades na execução das ações preventivas têm sido quase exclusivamente locais. O artigo relata uma pesquisa-intervenção baseada em oficinas sobre práticas preventivas realizadas antes do isolamento social, em 16 municípios das 5 regiões brasileiras, as quais envolveram um total de 379 participantes. Os resultados apresentam as ações preventivas preconizadas por campanhas que são as mais comumente compreendidas e executadas pela população; as situações que dificultam a execução; as práticas preventivas de iniciativa própria dos cidadãos; e as práticas baseadas em saberes populares. Ficou evidente que as informações fornecidas às comunidades não podem estar restritas às campanhas de massa, e que se faz necessário investir em ações educativas mais efetivas e adequadas à variedade de contextos nacionais, com vistas a construções coletivas e intersetoriais de estratégias de enfrentamento às arboviroses.

Abstract The environmental control of the vector inside and around households, as a fundamental strategy for the prevention of arboviruses such as dengue, zika and chikungunya, demands an uninterrupted involvement of the population. The pandemic context of Covid-19, and consequently the social isolation has reduced professional surveillance in the households, making the performance of the population even more necessary. Studies that seek to understand the involvement of communities in the implementation of preventive actions have been almost exclusively local. This article reports an intervention research based on workshops on preventive practices carried out before social isolation, in 16 municipalities in the five Brazilian regions and involved 379 participants. Our results show the preventive actions recommended by campaigns that are the most commonly understood and performed by the population; situations that hinder execution; preventive practices of citizens' own initiative; and practices based on popular knowledge. It became evident that information to communities cannot be restricted to mass campaigns, and that it is necessary to invest in educational actions adequate to the variety of national contexts, seeking collective and intersectoral constructions of strategies to confront arboviruses.

Prevention and control of dengue and chikungunya in Colombia: A cost-effectiveness analysis.

BACKGROUND: Chikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 -December 2017). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10-19 or 10-29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price. CONCLUSIONS/SIGNIFICANCE: Insecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases.

Model-based assessment of Chikungunya and O'nyong-nyong virus circulation in Mali in a serological cross-reactivity context.

Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O'nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation.

Determinants of Aedes mosquito density as an indicator of arbovirus transmission risk in three sites affected by co-circulation of globally spreading arboviruses in Colombia, Ecuador and Argentina.

BACKGROUND: The global impact of Zika virus in Latin America has drawn renewed attention to circulating mosquito-borne viruses in this region, such as dengue and chikungunya. Our objective was to assess socio-ecological factors associated with Aedes mosquito vector density as a measure of arbovirus transmission risk in three cities of potentially recent Zika virus introduction: Ibagué, Colombia; Manta, Ecuador; and Posadas, Argentina, in order to inform disease mitigation strategies. METHODS: We sampled Aedes mosquito populations in a total of 1086 households, using indoor and peridomestic mosquito collection methods, including light traps, resting traps, traps equipped with chemical attractant and aspirators. For each sampled household, we collected socio-economic data using structured questionnaires and data on microenvironmental conditions using iButton data loggers. RESULTS: A total of 3230 female Aedes mosquitoes were collected, of which 99.8% were Aedes aegypti and 0.2% were Aedes albopictus. Mean female Aedes mosquito density per household was 1.71 (standard deviation: 2.84). We used mixed-effects generalized linear Poisson regression analyses to identify predictors of Aedes density, using month, neighborhood and country as random-effects variables. Across study sites, the number of household occupants [incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 1.01-1.14], presence of entry points for mosquitoes into the household (IRR: 1.51, 95% CI: 1.30-1.76) and presence of decorative vegetation (IRR: 1.52, 95% CI: 1.22-1.88) were associated with higher Aedes density; while being in the highest wealth tertile of household wealth (IRR: 0.78, 95% CI: 0.66-0.92), knowledge of how arboviruses are transmitted (IRR: 0.94, 95% CI: 0.89-1.00) and regular emptying of water containers by occupants (IRR: 0.79, 95% CI: 0.67-0.92) were associated with lower Aedes density. CONCLUSIONS: Our study addresses the complexities of arbovirus vectors of global significance at the interface between human and mosquito populations. Our results point to several predictors of Aedes mosquito vector density in countries with co-circulation of multiple Aedes-borne viruses, and point to modifiable risk factors that may be useful for disease prevention and control.

Evaluating livestock farmers knowledge, beliefs, and management of arboviral diseases in Kenya: A multivariate fractional probit approach.

Globally, arthropod-borne virus (arbovirus) infections continue to pose substantial threats to public health and economic development, especially in developing countries. In Kenya, although arboviral diseases (ADs) are largely endemic, little is known about the factors influencing livestock farmers' knowledge, beliefs, and management (KBM) of the three major ADs: Rift Valley fever (RVF), dengue fever and chikungunya fever. This study evaluates the drivers of livestock farmers' KBM of ADs from a sample of 629 respondents selected using a three-stage sampling procedure in Kenya's three hotspot counties of Baringo, Kwale, and Kilifi. A multivariate fractional probit model was used to assess the factors influencing the intensity of KBM. Only a quarter of the farmers had any knowledge of ADs while over four-fifths of them could not manage any of the three diseases. Access to information (experience and awareness), income, education, religion, and distance to a health facility considerably influenced the intensity of farmers' KBM of ADs in Kenya. Thus, initiatives geared towards improving access to information through massive awareness campaigns are necessary to mitigate behavioral barriers in ADs management among rural communities in Kenya.