Central role of the placenta during viral infection: Immuno-competences and miRNA defensive responses

Pregnancy is a unique immunological condition in which an “immune-diplomatic” dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level.     

On realized serial and generation intervals given control measures: The COVID-19 pandemic case

The SARS-CoV-2 pathogen is currently spreading worldwide and its propensity for presymptomatic and asymptomatic transmission makes it difficult to control. The control measures adopted in several countries aim at isolating individuals once diagnosed, limiting their social interactions and consequently their transmission probability. These interventions, which have a strong impact on the disease dynamics, can affect the inference of the epidemiological quantities. We first present a theoretical explanation of the effect caused by non-pharmaceutical intervention measures on the mean serial and generation intervals. Then, in a simulation study, we vary the assumed efficacy of control measures and quantify the effect on the mean and variance of realized generation and serial intervals. The simulation results show that the realized serial and generation intervals both depend on control measures and their values contract according to the efficacy of the intervention strategies. Interestingly, the mean serial interval differs from the mean generation interval. The deviation between these two values depends on two factors. First, the number of undiagnosed infectious individuals. Second, the relationship between infectiousness, symptom onset and timing of isolation. Similarly, the standard deviations of realized serial and generation intervals do not coincide, with the former shorter than the latter on average. The findings of this study are directly relevant to estimates performed for the current COVID-19 pandemic. In particular, the effective reproduction number is often inferred using both daily incidence data and the generation interval. Failing to account for either contraction or mis-specification by using the serial interval could lead to biased estimates of the effective reproduction number. Consequently, this might affect the choices made by decision makers when deciding which control measures to apply based on the value of the quantity thereof.     

Examining the Ugandan health system’s readiness to deliver rheumatic heart disease-related services

BackgroundIn 2018, the World Health Assembly mandated Member States to take action on rheumatic heart disease (RHD), which persists in countries with weak health systems. We conducted an assessment of the current state of RHD-related healthcare in Uganda.Methodology/Principal findingsThis was a mixed-methods, deductive simultaneous design study conducted in four districts of Uganda. Using census sampling, we surveyed health facilities in each district using an RHD survey instrument that was modeled after the WHO SARA tool. We interviewed health workers with experience managing RHD, purposively sampling to ensure a range of qualification and geographic variation. Our final sample included 402 facilities and 36 health workers. We found major gaps in knowledge of clinical guidelines and availability of diagnostic tests. Antibiotics used in RHD prevention were widely available, but cardiovascular medications were scarce. Higher levels of service readiness were found among facilities in the western region (Mbarara district) and private facilities. Level III health centers were the most prepared for delivering secondary prevention. Health worker interviews revealed that limited awareness of RHD at the district level, lack of diagnostic tests and case management registries, and absence of clearly articulated RHD policies and budget prioritization were the main barriers to providing RHD-related healthcare.Conclusions/SignificanceUganda’s readiness to implement the World Health Assembly RHD Resolution is low. The forthcoming national RHD strategy must focus on decentralizing RHD diagnosis and prevention to the district level, emphasizing specialized training of the primary healthcare workforce and strengthening supply chains of diagnostics and essential medicines.     

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles

BackgroundDiagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment.Methology/principle findingsHere we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic.Conclusion/significancesOur results demonstrate nanoparticle technology’s potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.