Burden and distribution of dengue infection in Pakistan (2000-19): a review / Carga e distribuição geral de infecção por dengue no Paquistão entre 2000 e 2019: uma revisão

The goal of this study is to review the overall prevalence, burden, and distribution of the dengue disease in Pakistan from 2000 to 2019. Literature was searched using different search engines like Google scholar, PubMed, etc. providing the keywords "Dengue disease/infection, Dengue virus, DENV, DF/DHF/ DSS Pakistan". All the published research papers/reports on the dengue virus over the period 2000 to 2019 were studied and selected data were summarized using MS Excel for windows such as total cases, age wise, gender, DENV serotype distribution, total DHF, and DSS patients. The literature providing insufficient data was excluded. The total number of cases reported during 2000-19 were 201,269. The maximum number of cases during the mentioned literature survey period was reported in Khyber Pakhtunkhwa (KP) (23.3%) followed by Punjab (3.8%) and Sindh (1.9%). The majority of dengue-infected cases were reported as Dengue fever (74.4%) followed by DHF (24.1%) and DSS (1.5%). Overall the deaths during the mentioned literature survey were 1082, of which the maximum mortalities were reported from KP (N=248) followed by Punjab (N=220). DENV remains a major public health problem in Pakistan and seems to remain endemic for a long time. The total prevalence of dengue infection is increased accordingly with time from 2000 to 2019. Moreover, all the four serotypes exist in Pakistan with increased mortalities.

A literatura foi examinada através de diferentes mecanismos de pesquisa, como Google Acadêmico, PubMed, etc., fornecendo as palavras-chave "Dengue disease/infection, Dengue virus, DENV, DF/DHF/ DSS Pakistan". Todos os trabalhos/relatórios de pesquisa publicados sobre o vírus da dengue no período de 2000 a 2019 foram analisados e os dados selecionados foram coletados e resumidos usando o MS Excel para janelas como total de casos, idade, sexo, distribuição de sorotipos, total de DHF e pacientes com DSS. A literatura que forneceu dados insuficientes foi excluída. O número total de casos notificados de 2000 a 2019 foi de 201.269. O número máximo de casos durante o período de levantamento da literatura mencionado foi relatado em KP (23,3%), seguido por Punjab (3,8%) e Sindh (1,9%). A maioria dos casos de infecção por dengue foi relatada como Dengue (74,4%), seguida por FHD (24,1%) e DSS (1,5%). No geral, as mortes durante a pesquisa de literatura mencionada foram 1.082, das quais as morbidades máximas foram relatadas em KP (248), seguidas por Punjab, com um total de 220 mortes. O DENV continua sendo um grande problema de saúde pública no Paquistão e é considerado endêmico agora e provavelmente permanecerá por muito tempo. A prevalência total de infecção por dengue foi aumentada conforme a pesquisa de literatura publicada entre 2000 e 2019. A mortalidade por DENV também aumentou. Todos os 4 sorotipos, bem como em várias formas, existem no Paquistão.

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

Dengue disease in a pediatric patient with severe idiopathic pulmonary hypertension.

Dengue virus can affect the heart, with complications as bradycardia, arrhythmias, and death. We present a case of a 15-year-old patient, diagnosed 4 years before with severe idiopathic pulmonary hypertension, confirmed by catheterism, with continuous follow up. At that time, she was living in Bogotá (2640 m above sea level). Sildenafil and Macitentan were started. She was recommended to live at low altitude and she moved. The patient was transferred back to Bogota, from that place, due to flu-like symptoms and fever. Immunoglobulin M for dengue was confirmed and second-degree atrioventricular block Mobitz I with bradycardia (40 beats/minute) was documented throughout the clinical course. She recovered.

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

Environmental influences on antibody-enhanced dengue disease outcomes

Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE.

Características clínicas epidemiológicas de los cooperantes con dengue en el municipio Torres, estado de Lara, Venezuela, 2008 / Clinical and epidemiological characteristics of cooperation personnel diagnosed with dengue in the municipality of Torres, state of Lara, Venezuela, 2008

Se realizó un estudio descriptivo, de corte transversal, con el objetivo de identificar las características clínicas epidemiológicas de los cooperantes con dengue en el municipio Torres, en el estado de Lara, Venezuela, del 1ro. de junio de 2007 al 31 de julio de 2008. El universo de estudio quedó conformado por los 32 casos de dengue confirmados en el período de estudio. Se estudiaron las siguientes variables: edad, sexo, tipo de misión, factores de riesgos y las manifestaciones clínicas de los casos de dengue. Como medidas de resumen se utilizaron los números absolutos, frecuencias relativas, tasas, así como la determinación del índice de infestación a Aedes aegypti en las viviendas. Entre los principales resultados de la investigación se encontró que la morbilidad por dengue en los cooperantes del municipio Torres fue elevada, con una tasa de incidencia superior a la del Estado. En la muestra predominaron el sexo masculino y las edades entre 30 y 39 años. La mitad de los cooperantes de la misión agricultura enfermó de dengue. Entre los principales factores de riesgos se encontraron la presencia del vector y los criaderos en las viviendas, así como la baja percepción del riesgo sobre la enfermedad, lo que estuvo relacionado con el no uso de repelente, todos con un riesgo relativo mayor que 1. Las principales manifestaciones clínicas que se reportaron en los pacientes fueron la fiebre, la cefalea y la artralgia

A descriptive cross-sectional study was conducted with the purpose of identifying the clinical and epidemiological characteristics of cooperation personnel diagnosed with dengue in the municipality of Torres, state of Lara, Venezuela, from 1 June 2007 to 31 July 2008. The study group was composed of 32 dengue cases confirmed during the study period. The variables studied were age, sex, mission type, risk factors and clinical manifestations. The summary measurements used were absolute numbers, relative frequencies, rates, and household infestation rates for Aedes aegypti. One of the main findings of the study was the high dengue morbidity rate among cooperation personnel in the municipality of Torres, with an incidence rate higher than that of the state. Male sex and the 30-39 age range were predominant in the sample. Half the cooperation personnel in the agriculture mission became ill with dengue. Among the risk factors identified were the presence of the vector and breeding sites in households, and low risk perception of the disease, associated with the non-use of insect repellent. The relative risk of these factors was above 1. The main clinical manifestations observed in patients were fever, headache and arthralgia