Bayesian modeling of post-vaccination serological data suggests that yearly vaccination of dog aged <2 years old is efficient to stop rabies circulation in Cambodia.

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75-91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030.

Increased frequencies of highly activated regulatory T cells skewed to a T helper 1-like phenotype with reduced suppressive capacity in dengue patients.

The pathogenesis of dengue involves a complex interplay between the viral factor and the host immune response. A mismatch between the infecting serotype and the adaptive memory response is hypothesized to lead to exacerbated immune responses resulting in severe dengue. Here, we aim to define in detail the phenotype and function of different regulatory T cell (Treg) subsets and their association with disease severity in a cohort of acute dengue virus (DENV)-infected Cambodian children. Treg frequencies and proliferation of Tregs are increased in dengue patients compared to age-matched controls. Tregs from dengue patients are skewed to a Th1-type Treg phenotype. Interestingly, Tregs from severe dengue patients produce more interleukin-10 after in vitro stimulation compared to Tregs from classical dengue fever patients. Functionally, Tregs from dengue patients have reduced suppressive capacity, irrespective of disease severity. Taken together, these data suggest that even though Treg frequencies are increased in the blood of acute DENV-infected patients, Tregs fail to resolve inflammation and thereby could contribute to the immunopathology of dengue. IMPORTANCE: According to the World Health Organization, dengue is the fastest-spreading, epidemic-prone infectious disease. The extent of dengue virus infections increased over the years, mainly driven by globalization-including travel and trade-and environmental changes. Dengue is an immunopathology caused by an imbalanced immune response to a secondary heterotypic infection. As regulatory T cells (Tregs) are essential in maintaining immune homeostasis and dampening excessive immune activation, this study addressed the role of Tregs in dengue immunopathology. We show that Tregs from dengue patients are highly activated, skewed to a Th1-like Treg phenotype and less suppressive compared to healthy donor Tregs. Our data suggest that Tregs fail to resolve ongoing inflammation during dengue infection and hence contribute to the immunopathology of severe dengue disease. These data clarify the role of Tregs in dengue immunopathogenesis, emphasizing the need to develop T cell-based vaccines for dengue.

An Entomological Investigation during a Recent Rift Valley Fever Epizootic/Epidemic Reveals New Aspects of the Vectorial Transmission of the Virus in Madagascar.

A Rift Valley fever (RVF) outbreak occurred in at least five regions of Madagascar in 2021. The aim of this study was to provide an overview of the richness, abundance, ecology, and trophic preferences of mosquitoes in the Mananjary district and to investigate the distribution of mosquitoes that were RT-PCR-positive for RVFV. Three localities were prospected from 26 April to 4 May 2021, using light traps, BG-Sentinel traps baited with an artificial human odor, Muirhead-Thomson pit traps, and indoor pyrethroid spray catches. A total of 2806 mosquitoes belonging to at least 26 species were collected. Of 512 monospecific pools of mosquitoes tested with real-time RT-PCR, RVFV was detected in 37 pools representing 10 mosquito species. The RVFV-positive species were as follows: Aedes albopictus, Ae. argenteopunctatus, Anopheles coustani, An. gambiae s.l., An. mascarensis, An. squamosus/cydippis, Culex antennatus, Cx. decens, Cx. Tritaeniorhynchus, and Uranotaenia spp. Of the 450 tested engorged females, 78.7% had taken a blood meal on humans, 92.9% on cattle, and 71.6% had taken mixed (human-cattle) blood meals. This investigation suggests the potential role of mosquitoes in RVFV transmission within this epizootic/epidemic context and that the human populations at the three study sites were highly exposed to mosquitoes. Therefore, the use of impregnated mosquito nets as an appropriate prevention method is recommended.

The Re-Emergence of Rift Valley Fever in Mananjary District, Madagascar in 2021: A Call for Action.

An epizootic of rift valley fever (RVF) was suspected on 21 February 2021 in various districts of Madagascar, with a lab confirmation on 1 April 2021. A cross-sectional survey aiming to detect cases of RVF in humans and to study the circulation of rift valley fever virus (RVFV) in animals was conducted from 22 April to 4 May 2021 in the district of Mananjary. Blood samples from cattle and humans were tested using serological and molecular techniques. In cattle, the circulation of RVFV was confirmed between 5 February and 4 May 2021. The positivity rates of anti-RVFV IgG and IgM were 60% and 40%, respectively. In humans, the circulation of RVFV was observed from 1 April to 5 May 2021. The positivity rate of RVFV was estimated to be 11.7% by combining the results of the molecular and serological approaches. Of the 103 individuals who agreed to participate in the survey, 3 were determined to be positive by RT-PCR, and 10 had anti-RVFV IgM. Among them, one was positive for both. Given that previous studies have reported the circulation of RVFV during inter-epidemic periods and the occurrence of outbreaks due to imported RVFV in Madagascar, our findings suggest the importance of strengthening RVF surveillance from a "One Health" perspective by conducting syndromic and risk-based surveillance at the national and regional levels.

Challenges of rabies surveillance in Madagascar based on a mixed method survey amongst veterinary health officers.

Introduction: In Madagascar, rabies is endemic and a notifiable disease. The objective of this mixed study was to understand the challenges faced by the Veterinary Health Officers (VHOs) in the current rabies surveillance system in Madagascar. Methods: A survey was conducted from mid-April to the end of July 2021 during which all officially-listed VHOs (N = 150) were contacted by phone at least twice. Participants, representative of the 22 regions of Madagascar, were interviewed by phone based on a semi-structured questionnaire on (1) their knowledge of rabies epidemiology in their area of activities, (2) the occurrence of human and animal rabies and the species affected in the region where they work, (3) the factors that might influence rabies surveillance depending on (a) their activities and area of operation, (b) the socio-cultural aspects of local communities, and (c) the general organization of animal rabies surveillance. Results: The majority (80/90) of VHOs declared having been informed of at least one suspected or confirmed case of human and/or animal rabies in their area of activity during their work as VHOs: at least once a month for 11 of them, at least once a year for 40 and with undetermined frequency for 29. Several obstacles hinder the surveillance of rabies resulting in under-reporting. The lack of funds to access suspect animals, collect, pack and ship samples in compliance with biosecurity measures and the cold chain, was mentioned as a major obstacle to surveillance. The second barrier is socio-cultural: in many large coastal regions, dogs are taboo and VHOs fear rejection by the community if they treat dogs. Discussion and conclusion: While the general population requires information on the rabies situation in Madagascar and on how to proceed in the event of a bite, veterinarians and decision-makers need to be fully aware of an evidence-based approach to rabies surveillance, prevention and control. Communication between the human and animal health sectors should be improved. Politicians need to be persuaded of the importance of funding to eliminate rabies in Madagascar. The adoption, in early 2023, of a national strategic plan for rabies control is a first step in this direction.

Hospitalized cases of influenza A(H1N1)pdm09 in the French territories of the Americas, July 2009–March 2010 / Casos hospitalizados de gripe A(H1N1)pdm09 en los territorios franceses de las Américas entre julio de 2009 y marzo de 2010

Objective. To describe the methodology used for implementing a surveillance system specifically for influenza A(H1N1)pdm09 in the French West Indies and French Guiana during an outbreak of this new virus in 2009­2010, and to report its main results. Methods. This was an observational descriptive study of confirmed and probable cases of influenza A(H1N1)pdm09 hospitalized for at least 24 hours in 23 July 2009­3 March 2010. Reverse transcription polymerase chain reaction was performed on nasopharyngeal swab samples according to the Centers for Disease Control and Prevention protocol. A probable case was defined as fever ≥ 38°C or aches or asthenia with respiratory symptoms (cough or dyspnea). All confirmed and probable hospitalized cases were reported, along with patient's age, sex, clinical condition at admission, place and length of hospitalization, antiviral treatment, underlying conditions, complications, and clinical evolution. A case was classified as severe if respiratory assistance or intensive care was required or if death resulted. Results. A total of 331 confirmed and 16 probable cases were hospitalized, with a hospitalization rate ranging from 4.3 per 1 000 clinical cases in Saint Martin to 10.3 in French Guiana. Of these, 36 were severe, and subsequently, 10 were fatal. The median length of stay was 4 days for non-severe cases and 9 days for severe (P < 0.05). The mean patient age was 21 years, and severe cases were significantly older than non-severe (mean: 38 years versus 19 years, P < 0.05). Underlying conditions associated with a higher risk of severity were 65 years of age or more (RR = 7.5, 95%CI = 4.2­13.3), diabetes (RR = 3.7, 95%CI = 1.5­9.4), cardiac insufficiency (RR = 8.4, 95%CI = 5.2­13.6), and morbid obesity (RR = 4.4, 95%CI = 1.8­ 10.4). Patients who received antiviral treatment within 2 days of symptom onset had shorter hospital stays (mean: 4 days versus 6.5 days, P < 0.05), and the illness tended to become less severe (11.1% versus 19.0%, P = 0.13). Conclusions. Active research of hospitalized cases enabled almost exhaustive surveillance. The pandemic's hospitalization rates and lethality were more moderate than expected. Some previously known underlying conditions of severity were confirmed dur.

Objetivo. Describir la metodología usada para implementar un sistema de vigilancia específico para la gripe A(H1N1)pdm09 en las Indias Occidentales Francesas y la Guayana Francesa durante un brote ocasionado por este virus nuevo ocurrido en 20092010 y presentar sus principales resultados. Métodos. Se llevó a cabo un estudio de observación descriptivo de los casos confirmados y probables de gripe por A(H1N1)pdm09 hospitalizados durante al menos 24 horas entre el 23 de julio de 2009 y el 3 de marzo de 2010. De conformidad con el protocolo de los Centros para el Control y la Prevención de Enfermedades se realizó la prueba de reacción en cadena de la polimerasa con transcripción inversa en muestras de hisopados nasofaríngeos. Se definió como caso probable la presencia de fiebre ≥ 38 °C o dolores o astenia junto con síntomas respiratorios (tos o disnea). Se comunicaron todos los casos hospitalizados confirmados y probables junto con la edad, el sexo, la situación clínica del paciente en el momento del ingreso, el lugar y la duración de la hospitalización, el tratamiento antivírico, las enfermedades subyacentes, las complicaciones y la evolución clínica. Se clasificaron como graves los casos que requirieron asistencia respiratoria o cuidados intensivos o provocaron la muerte. Resultados. Fueron hospitalizados en total 331 casos confirmados y 16 probables, con una tasa de hospitalización que osciló entre 4,3 por cada 1 000 casos clínicos en San Martín y 10,3 por cada 1 000 en la Guayana Francesa. De ellos, 36 fueron graves y 10 llevaron posteriormente a la muerte del paciente. La mediana de la duración de las hospitalizaciones fue de 4 días para los casos no graves y de 9 días para los graves (P < 0,05). La edad media de los pacientes fue de 21 años, y los casos graves fueron significativamente de mayor edad que los no graves (media: 38 años frente a 19 años; P < 0,05). Las enfermedades subyacentes asociadas con un riesgo mayor de gravedad fueron edad de 65 años o más (RR = 7,5; IC de 95% = 4,213,3), diabetes (RR = 3,7; IC de 95% = 1,59,4), insuficiencia cardíaca (RR = 8,4; IC de 95% = 5,213,6) y obesidad mórbida (RR = 4,4; IC de 95% = 1,810,4). En los pacientes que recibieron tratamiento antivírico en el plazo de 2 días de la aparición de los síntomas las estancias hospitalarias fueron más breves (media: 4 días frente a 6,5 días; P < 0,05) y la enfermedad tendió a presentar menor gravedad (11,1% frente a 19,0%; P = 0,13). Conclusiones. La investigación activa de los casos hospitalizados permitió una vigilancia casi exhaustiva. Las tasas de hospitalización y la letalidad de la pandemia fueron más moderadas que lo previsto. Durante este brote se confirmó la capacidad de algunas enfermedades subyacentes ya conocidas para aumentar la gravedad. Además, estos resultados demuestran la validez del tratamiento antivírico temprano