Papers by Mireia Navarro Gabriel
Eurosurveillance
A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples ... more A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples collected at different time points from 12 patients by real-time PCR. MPX DNA was detected in saliva from all cases, sometimes with high viral loads. Other samples were frequently positive: rectal swab (11/12 cases), nasopharyngeal swab (10/12 cases), semen (7/9 cases), urine (9/12 cases) and faeces (8/12 cases). These results improve knowledge on virus shedding and the possible role of bodily fluids in disease transmission.
Microbiology Spectrum
The rapid detection of people infected with SARS-CoV-2 is essential for a correct and effective c... more The rapid detection of people infected with SARS-CoV-2 is essential for a correct and effective control of the disease it causes. This process must be sensitive, fast, and simple, and it must be possible to carry out in any type of health center.
Infection
Purpose Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcriptio... more Purpose Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. Methods Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni-and multivariate analyses were performed to identify factors associated with mortality at 60 days. Results Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). Conclusions The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals. Keywords COVID-19 • Viral load • Ct value • Days of symptoms • Mortality The members of COVID-19-Researcher Group are listed in Acknowledgements.
BMJ Global Health
BackgroundGlobal malaria mortality estimates are hindered by the low reliability of the verbal au... more BackgroundGlobal malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard.MethodsObservational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry)...
PLOS Neglected Tropical Diseases, 2021
BackgroundHistoplasmosis is acquired by inhalation of spores of the dimorphic fungusHistoplasma s... more BackgroundHistoplasmosis is acquired by inhalation of spores of the dimorphic fungusHistoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions.MethodologyWe conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization ofHistoplasmastrains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation.Principal findingsEvidence ofHistoplasmainfection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patientsHistoplasmaDNA was detected by PCR in patients with no his...
Parasite kinetics measured by qPCR from Groups 1 (2,500 10μL IM), 5 (25,000 10μL IM) and 6 (75,00... more Parasite kinetics measured by qPCR from Groups 1 (2,500 10μL IM), 5 (25,000 10μL IM) and 6 (75,000 10μL IM). This figure shows parasite densities measured by qPCR, plotted in a single chart and different colors per group, from Groups inoculated by IM injection with increasing doses of 2,500 PfSPZ, 25,000 PfSPZ and 75,000 PfSPZ in a volume of 10μL. The higher the PfSPZ dose inoculated, the sooner sub-microscopic parasite densities are detected. Density units are in parasites/mL. Limit of quantification of qPCR was 30 parasites per mL.
Type and number of grade 3 adverse events or laboratory abnormalities in the erythrocytic phase –... more Type and number of grade 3 adverse events or laboratory abnormalities in the erythrocytic phase – after initiation of treatment of malaria or Day 21 until the end of follow up visits on Day 90. This table provides a list of grade 3 AEs or laboratory abnormalities observed after initiation of treatment of malaria or Day 21 until the end of follow up visits on Day 90, in the different inoculation groups.
Pathogens, 2021
Postmortem studies are crucial for providing insight into emergent diseases. However, a complete ... more Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the...
Viruses, 2021
Dengue is the most significant arbovirus worldwide and a public health threat to non-endemic area... more Dengue is the most significant arbovirus worldwide and a public health threat to non-endemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global c...
The objective of this study was to assess the performance of direct real time RT-PCR detection of... more The objective of this study was to assess the performance of direct real time RT-PCR detection of SARS-CoV-2 in heated saliva samples, avoiding the RNA isolation step. Oropharyngeal and nasopharyngeal swabs together with saliva samples were obtained from 51 patients clinically diagnosed as potentially having COVID-19. Two different methods were compared: 1. RNA was extracted from 500 μl of sample using a MagNA Pure Compact Instrument with an elution volume of 50μl and 2. 700µL of saliva were heat-inactivated at 96°C for 15 minutes, and directly subjected to RT-PCR. One step real time RT-PCR was performed using 5 μl of extracted RNA or directly from 5 μl of heated sample. RT-PCR was performed targeting the SARS-CoV-2 envelope (E) gene region. Diagnostic performance was assessed using the results of the RT-PCR from nasopharyngeal and oropharyngeal swabs as the gold standard. The overall sensitivity, specificity, positive and negative predictive values were 81.08%, 92.86%, 96.77% and 6...
Chest, 2021
An estimated 1.5 million deaths were attributable to TB in 2018. 1 However, some uncertainty exis... more An estimated 1.5 million deaths were attributable to TB in 2018. 1 However, some uncertainty exists as to the exact global figures, given that approximately 30% of incident cases are not diagnosed, and because of the difficulties of ascertaining TB as cause of death (CoD). 2 Undoubtedly, complete diagnostic autopsies (CDAs) constitute the gold standard for establishing a diagnosis of TB at death. However, CDAs are seldom performed in high-TB-burden countries because of the scarcity of trained pathologists, the time-consuming nature of the procedure, and the meager acceptability of the practice by relatives. 3
European Respiratory Journal, 2019
Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, e... more Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivit...
Scientific Reports, 2019
Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in ad... more Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patient...
Scientific reports, Jan 31, 2018
Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive au... more Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), an innovative approach to post-mortem sampling and cause of death investigation, are commonly performed within 24 hours after death because the quality of the tissues deteriorates over time. This short timeframe may hamper the feasibility of the procedure. In this study, we compared the diagnostic performance of the two postmortem procedures when carried out earlier and later than 24 hours after death, as well as the impact of increasing postmortem intervals (PMIs) on the results of the microbiological tests in a series of 282 coupled MIA/CDA procedures performed at the Maputo Central Hospital in Mozambique between 2013 and 2015. 214 procedures were conducted within 24 hours of death (early autopsies), and 68 after 24 hours of death (late autopsies). No significant differences were observed in the number of non-conclusive diagnoses (2/214 [1%] vs. 1/68 [1%] p = 0.5645 for th...
PLoS medicine, 2017
In recent decades, the world has witnessed unprecedented progress in child survival. However, our... more In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting. In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive...
PLOS Medicine, 2016
Background There is an urgent need to identify tools able to provide reliable information on the ... more Background There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique.
Malaria Journal, 2015
Background: Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for eva... more Background: Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. Methods: An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). Results: Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. Conclusions: IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ
Clinical Infectious Diseases, 2021
Background Available information on the causes of death among people living with human immunodefi... more Background Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. Methods We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. Results Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas vira...
Transplant international : official journal of the European Society for Organ Transplantation, Aug 23, 2018
In 2011, the first Direct Acting Antiviral (DAA) agent was approved for HCV treatment, with high ... more In 2011, the first Direct Acting Antiviral (DAA) agent was approved for HCV treatment, with high rates of sustained viral response (SVR). Absence of RNA-HCV viral load 12 weeks after end of treatment is considered as permanent viral eradication. However anti-HCV could remain positive despite successful antiviral therapy2.Moreover,HCV can infect extrahepatic tissues, including kidney. The infected extrahepatic tissues might play a role in both HCV persistence and reactivation of infection. This article is protected by copyright. All rights reserved.
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Papers by Mireia Navarro Gabriel