Browsing by Author "Marco, Claudia"
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Publication A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus(International Medical Press, 2015) Vial, Pablo; Valdivieso, Francisca; Calvo, Mario; Rioseco, María; Riquelme, Raúl; Araneda, Andrés; Tomicic, Vinko; Graf, Jerónimo; Paredes, Laura; Fiorenzano, Matías; Bidart, Teresa; Cuiza, Analía; Marco, Claudia; Hjelle, Brian; Ye, Chunyan; Hanfelt-Goade, Daniel; Vial, Cecilia; Rivera, Juan; Mertz, Gregory; Hantavirus Study Group in Chile; Delgado, IrisBACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.Item A Single-Nucleotide Polymorphism of αVβ3 Integrin Is Associated with the Andes Virus Infection Susceptibility(2019) Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Corre, Nicole Le; Marco, Claudia; Vial, Cecilia; Miquel, Juan Francisco; Cerda, Jaime; Mertz, Gregory; Vial, Pablo; Lopez-Lastra, Marcelo; Ferrés, MarcelaThe Andes Orthohantavirus (ANDV), which causes the hantavirus cardiopulmonary syndrome, enters cells via integrins, and a change from leucine to proline at residue 33 in the PSI domain (L33P), impairs ANDV recognition. We assessed the association between this human polymorphism and ANDV infection. We defined susceptible and protective genotypes as “TT” (coding leucine) and “CC” (coding proline), respectively. TT was present at a rate of 89.2% (66/74) among the first cohort of ANDV cases and at 60% (63/105) among exposed close-household contacts, who remained uninfected (p < 0.05). The protective genotype (CC) was absent in all 85 ANDV cases, in both cohorts, and was present at 11.4% of the exposed close-household contacts who remained uninfected. Logistic regression modeling for risk of infection had an OR of 6.2–12.6 (p < 0.05) in the presence of TT and well-known ANDV risk activities. Moreover, an OR of 7.3 was obtained when the TT condition was analyzed for two groups exposed to the same environmental risk. Host genetic background was found to have an important role in ANDV infection susceptibility, in the studied population.Item Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011(Centers for Desease Control and Prevention, 2014) Martinez-Valdebenito, Constanza; Calvo, Mario; Vial, Cecilia; Mansilla, Rita; Marco, Claudia; Palma, Eduardo; Vial, Pablo; Valdivieso, Francisca; Mertz, Gregory; Ferrés, MarcelaAndes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms.Item Typhoid Fever in Chile 1969-2012: Analysis of an Epidemic and Its Control(2018) Marco, Claudia; Delgado, Iris; Vargas, Claudio; Muñoz, Ximena; Bhutta, Zulfiqar; Ferreccio, CatterinaFrom 1975 to 1983, a large epidemic of typhoid fever (TF) affected the metropolitan region (MR) of Chile (incidence rate [IR] of 219.6 per 105 in 1983). In 1983-1984, interventions were implemented focusing on person-to-person transmission (vaccination, food handlers' control, and mass communication) and regulations to control irrigation waters containing fecal contaminates. In 1991, a second intervention was quickly implemented to avoid the cholera epidemic affecting neighboring countries (total prohibition of growing or selling crops in the MR). We explored the potential impact of these interventions on the epidemic. We created a yearly database of the MR TF cases, population, and contextual factors of TF from 1969 to 2012. We first analyzed the epidemic (Joinpoint regression), identified predictors of TF (Poisson multiple regression), and then analyzed the effect of the interventions (interrupted time series model). The main predictor of the TF epidemic was the rate of unemployment. In relation to the 1983-1984 person-to-person interventions, TF came down by 51% (95% confidence interval [CI]: 30.2-65.0%) and continued to decrease at a rate of 10.4% (95% CI: 5.8-15.6%) per year until 1991. In 1991, with the strong environmental control of the sewage-irrigated crops, TF further decreased by 77% (95% CI: 69.0-83.1%) and continued decreasing thereafter at 13% (95% CI: 11.3-15.6%) per year until the end of the study period. Today, 40 years after the epidemic, TF is a rare disease in the MR of Chile.Publication Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study(2024) Ferrés, Marcela; Martínez, Constanza; Henriquez, Carolina; Marco, Claudia; Barrera, Aldo; Palma, Carlos; Barriga, Gonzalo; Cuiza, Analia; Ferreira, Leonila; Rioseco, María; Calvo, Mario; Fritz, Ricardo; Bravo, Sebastián; Bruhn, Alejandro; Graf, Jerónimo; Llancaqueo, Alvaro; Rivera, Gonzalo; Cerda, Carolina; Tischler, Nicole; Valdivieso, Francisca; Vial, Pablo; Mertz, Gregory; Vial Cox, María Cecilia; Le Corre, NicoleBackground: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. Methods: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. Findings: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). Interpretation: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. Funding: National Institutes of Health and Agencia de Investigación y Desarrollo.