Epidemiological and clinical features of the 2016-2018 Zika virus outbreak in northern Argentina.

BACKGROUND: During the American epidemic, Zika virus (ZIKV) expanded rapidly through dengue virus (DENV)-endemic regions. We analyzed the presentation of ZIKV infection in patients from the City of Orán, Argentina, and compared some of its features with dengue presentation in the same region. METHODS: A retrospective study was conducted at San Vicente de Paul Hospital during 2016-2018. Clinical and demographic characteristics, pre-existing immunity to DENV, viral load and type I interferon (IFN) responses were studied in 63 patients with ZIKV infection. RESULTS: Clinical manifestations of ZIKV infection were generally mild compared with dengue, although rash (p<0.001) and itching (p<0.001) were significantly more prevalent in ZIKV patients. ZIKV patients aged <15 y manifested relatively mild disease compared with older ZIKV patients, showing a decreased prevalence of headache (p=0.008), retro-orbital pain (p=0.001) and arthralgia (p=0.001). Increased Zika incidence was observed in female patients (60.3%). Serum viral load was low to undetectable in ZIKV patients and was not associated with serum anti-DENV IgG titers. Interferon-α and IFN-ß serum levels did not correlate with serum viral load in ZIKV patients. CONCLUSIONS: Clinical presentation of ZIKV and DENV infections is largely overlapping, presenting a challenge for diagnosis and risk assessment for uniquely at-risk populations.

Hantavirus pulmonary syndrome outbreaks associated with climate variability in Northwestern Argentina, 1997-2017.

BACKGROUND: Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%-50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors. METHODOLOGY AND MAIN FINDINGS: We compiled reported HPS cases in northwestern Argentina during the 1997-2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.

Utilidad de un sistema de registro de una derivación electrocardiográfica y transmisión inalámbrica durante la pandemia por COVID-19 / Electrocardiographic Recording System and Wireless Transmission During the COVID-19 Pandemic

RESUMEN Introducción: Se ha comunicado que algunos tratamientos utilizados para la infección por COVID-19 pueden ocasionar alteraciones del intervalo QT y arritmias graves. La medición por electrocardiograma (ECG) convencional requiere personal adicional y riesgo de contagio. Nuevas tecnologías para obtención de un ECG conectados a teléfonos inteligentes (smartphones) proporcionan una alternativa para evaluación del QTc. Objetivo: El objetivo fue evaluar la factibilidad de un dispositivo para registro electrocardiográfico de un canal, para la medición del intervalo QT en pacientes con sospecha o confirmación de infección por COVID-19, antes de recibir drogas que prolongan el intervalo QT. Material y métodos: Se obtuvieron registros de ECG con un dispositivo Kardia Mobile (KM) con trasmisión a un smarthphone. La sección de electrofisiología cardíaca centralizó la recepción por medio electrónico de los ECG en formato de archivo pdf y realizó las mediciones de los intervalos QTm y QTc. Resultados: Se estudiaron 31 pacientes, edad promedio 61 años (rango 20-95 años), sospechosos de presentar infección por COVID-19 enrolados para tratamiento con hidroxicloroquina, azitromicina, ritonavir y lopinavir. Los registros pudieron ser leídos en todos los casos, y debieron repetirse en dos casos. Los valores del intervalo QTc promedio en varones y mujeres fue 423 mseg (rango 380-457 mseg) y 439 mseg (rango 391-540 mseg), respectivamente. El tiempo de respuesta desde el envío del ECG al grupo de análisis fue 11 min (rango 1-155). Conclusiones: Los registros ECG obtenidos con dispositivos KM, para trasmisión a un smartphone a un grupo central de lectura, permitieron la medición del intervalo QTc en todos los pacientes.

ABSTRACT Background: Some therapies used for COVID-19 can prolong the QT interval and produce severe arrhythmias. QT interval measured from a standard electrocardiogram (ECG) requires additional personnel and risk of infection. Novel technologies to obtain an ECG connected to smartphones provide an alternative for the evaluation of corrected QT interval (QTc). Objective: The aim of this study was to evaluate the feasibility of using a single-lead ECG device to measure the QT interval in patients with suspected or confirmed COVID-19 before receiving treatment with drugs that can prolong the QT interval. Methods: The ECG was obtained with a KardiaMobile (KM) device and transmitted to a smartphone. The ECG recordings were saved as pdf files and electronically submitted to the electrophysiology section which centralized the reception and assessed the measured QT and QTc intervals. Results: A total of 31 patients (mean age 61 years, range 20-95 years) with suspected COVID-19 enrolled for treatment with hydroxychloroquine, azithromycin, ritonavir or lopinavir were analyzed. The recordings could be read in all the cases and had to be repeated in two cases. The mean value of the QTc interval was 423 ms (range 380-457 ms) in men and 439 ms (range 391-540 ms) in women. The response time since the ECG recording was submitted for analysis was 11 min (range 1-155). Conclusions: The QTc interval could be measured from ECG recordings obtained with KM devices connected to a smartphone and transmitted to a centralized reading center in all patients.

COVID-19: plasma de convaleciente en la sala de Clínica Médica del Hospital Gral. de Agudos "Dr. Cosme Argerich" en Buenos Aires / Convalescent plasma in Internal Medicine Ward from Hospital Argerich in Buenos Aires

Se presentan los resultados de seguridad y evolución clínica de 87 pacientes que recibieron plasma de convaleciente en la sala de Clínica Médica del Hospital Argerich en Buenos Aires. Tres pacientes tuvieron sobrecarga de volumen. Hubo 33 pases a Terapia Intensiva (37,9%) y 21 casos requirieron asistencia respiratoria mecánica (24,1%). Fallecieron 18 pacientes (20,7%). Tres de ellos por limitación del esfuerzo terapéutico y 15 en Terapia Intensiva. La mortalidad en Terapia Intensiva fue del 45,4%. Hubo solo 10 casos que recibieron plasma dentro de las 72 horas del comienzo de síntomas: de ellos, 1 caso de asistencia respiratoria y 1 fallecido; entre 72 horas y una semana recibieron plasma 25 casos con 26,9% de asistencia respiratoria y 20% de mortalidad, y de los 50 pacientes que recibieron mas allá de la primera semana, 25,4% requirieron de asistencia respiratoria y 24% fallecieron. Nuestra serie no pudo demostrar efecto beneficioso en la administración temprana de plasma y no fue diseñada para medir eficacia. El procedimiento fue bien tolerado en la gran mayoría de los pacientes

We present here the results of safety and clinical outcome of 87 patients that received convalescent plasma transfusion in the internal medicine ward of Hospital Argerich in Buenos Aires. Three patients developed transfusion-associated circulatory overload. Thirty-three patients were admitted to Intensive Care Unit (37,9%) and 21 cases required mechanical ventilation. Eighteen patients died (20,7%), 3 of them due to limitation of therapeutic effort and 15 in ICU. The mortality in ICU was 45,4%. Ten patients received plasma within 72 hs from the onset of symptoms. Of them, 1 case required mechanical ventilation and died. Twenty-five patients received plasma between 4 and 7 days from onset of symptoms, with a mortality rate of 20% and 26,9% of mechanical ventilation. Fifty patients received plasma past the 7 days from onset of symptoms, with a mortality rate of 24% and 25,4% of mechanical ventilation. Our series could not prove positive effects in the early administration of plasma and it was not designed to measure effectiveness. The procedure was well tolerated by most of the patients

Epidemiological description, case-fatality rate, and trends of Hantavirus Pulmonary Syndrome: 9 years of surveillance in Argentina.

Hantavirus pulmonary syndrome (HPS) is an endemic disease in Argentina, one of the most affected countries in the Americas. Andes virus (ANDV) is the main Orthohantavirus species causing HPS in Argentina. In this study, the geographical distribution, clinical presentation, and epidemiological features of HPS from all endemic regions of Argentina were analyzed. We focused on the clinical and epidemiological data from 533 HPS cases confirmed during the period 2009 to 2017 by the National Reference Laboratory for Hantavirus. A case-fatality rate of 21.4% was registered, and most of the cases presented a severe clinical picture requiring intensive care treatment (84%). Since HPS first detection in 1995 the case-fatality rate showed a general trend towards a decrease. After more than 22 years of experience in HPS diagnosis and surveillance, we discuss some possible factors implicated in this tendency. This clinical and epidemiological analysis gives a global perspective, being useful to detect trends and patterns, to update preventive actions at a national level, and evaluate their impact on public health.

Age-associated differences in clinical manifestations and laboratory parameters during a dengue virus type 4 outbreak in Argentina.

Infection by any of the four dengue virus (DENV) serotypes produces a wide spectrum of clinical illness in humans. Differences in clinical manifestation and severity have been associated with secondary heterologous infection, patient age, and virus serotype. In this context, this retrospective study sought to analyze the presentation of dengue in patients during the 2014 DENV-4 outbreak affecting the City of Orán, Salta Province, Argentina. Demographic data, clinical manifestations, and laboratory abnormalities of laboratory-confirmed dengue patients were compared between age groups and between patients with and without warning signs. Of 301 patients with laboratory-confirmed dengue, 37.9% presented dengue with warning signs. Although nearly half of all patients had secondary DENV infections, no severe dengue cases, or deaths were reported. Furthermore, no association was found between incidence of warning signs and pre-existing immunity to DENV. Pediatric patients were least likely to present warning signs and showed significantly decreased risk of fever, retro-orbital pain, arthalgia, diarrhea and thrombocytopenia, and higher risk of rash compared to older patients. Female patients of all ages were also at higher risk of developing several symptoms. The characterization of DENV-4 infection in humans, a DENV serotype recently reported in Argentina, revealed differences in clinical manifestations, laboratory parameters and the presence/absence of warning signs based on age group. Further investigation of these age-related differences should contribute to better assessment of dengue disease in at risk populations.

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3neg CD19low CD20neg CD38hi CD27hi CD138+/- IgA+/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker.