Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India.

BACKGROUND AND AIMS: Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID). APPROACH AND RESULTS: We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. CONCLUSIONS: This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.

Long-term, infection-acquired immunity against the SARS-CoV-2 Delta variant in a hamster model.

The emergence of the SARS-CoV-2 Delta variant (B.1.617.2) raises concerns about potential reduced sensitivity of the virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we use a live virus neutralization assay with sera from Pfizer- and Moderna-vaccinated individuals to examine neutralizing antibody titers against SARS-CoV-2 and observe a 3.9- and 2.7-fold reduction, respectively, in neutralizing antibody titers against the Delta variant compared with an early isolate bearing only a D614G substitution in its spike protein. We observe similar reduced sensitivity with sera from hamsters that were previously infected with an early isolate of SARS-CoV-2. Despite this reduction in neutralizing antibody titers against the Delta variant, hamsters previously infected (up to 15 months earlier) with an early isolate are protected from infection with the Delta variant, suggesting that the immune response to the first infection is sufficient to provide protection against subsequent infection with the Delta variant.

SARS-CoV-2 infection induces protective immunity and limits transmission in Syrian hamsters.

A critical question in understanding the immunity to SARS-COV-2 is whether recovered patients are protected against re-challenge and transmission upon second exposure. We developed a Syrian hamster model in which intranasal inoculation of just 100 TCID50 virus caused viral pneumonia. Aged hamsters developed more severe disease and even succumbed to SARS-CoV-2 infection, representing the first lethal model using genetically unmodified laboratory animals. After initial viral clearance, the hamsters were re-challenged with 105 TCID50 SARS-CoV-2 and displayed more than 4 log reduction in median viral loads in both nasal washes and lungs in comparison to primary infections. Most importantly, re-challenged hamsters were unable to transmit virus to naïve hamsters, and this was accompanied by the presence of neutralizing antibodies. Altogether, these results show that SARS-CoV-2 infection induces protective immunity that not only prevents re-exposure but also limits transmission in hamsters. These findings may help guide public health policies and vaccine development and aid evaluation of effective vaccines against SARS-CoV-2.

SARS-CoV-2: lessons from both the history of medicine and from the biological behavior of other well-known viruses.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

Complete Analysis of the Epidemiological Scenario around a SARS-CoV-2 Reinfection: Previous Infection Events and Subsequent Transmission.

The first descriptions of reinfection by SARS-CoV-2 have been recently reported. However, these studies focus exclusively on the reinfected case, without considering the epidemiological context of the event. Our objectives were to perform a complete analysis of the sequential infections and community transmission events around a SARS-CoV-2 reinfection, including the infection events preceding it, the exposure, and subsequent transmissions. Our analysis was supported by host genetics, viral whole-genome sequencing, phylogenomic viral population analysis, and refined epidemiological data obtained from interviews with the involved subjects. The reinfection involved a 53-year-old woman with asthma (Case A), with a first COVID-19 episode in April 2020 and a much more severe second episode 4-1/2 months later, with SARS-CoV-2 seroconversion in August, that required hospital admission. An extended genomic analysis allowed us to demonstrate that the strain involved in Case A's reinfection was circulating in the epidemiological context of Case A and was also transmitted subsequently from Case A to her family context. The reinfection was also supported by a phylogenetic analysis, including 348 strains from Madrid, which revealed that the strain involved in the reinfection was circulating by the time Case A suffered the second episode, August-September 2020, but absent at the time range corresponding to Case A's first episode. IMPORTANCE We present the first complete analysis of the epidemiological scenario around a reinfection by SARS-CoV-2, more severe than the first episode, including three cases preceding the reinfection, the reinfected case per se, and the subsequent transmission to another seven cases.

Mathematical Modelling of COVID-19 Transmission in Kenya: A Model with Reinfection Transmission Mechanism.

In this study we propose a Coronavirus Disease 2019 (COVID-19) mathematical model that stratifies infectious subpopulations into: infectious asymptomatic individuals, symptomatic infectious individuals who manifest mild symptoms and symptomatic individuals with severe symptoms. In light of the recent revelation that reinfection by COVID-19 is possible, the proposed model attempt to investigate how reinfection with COVID-19 will alter the future dynamics of the recent unfolding pandemic. Fitting the mathematical model on the Kenya COVID-19 dataset, model parameter values were obtained and used to conduct numerical simulations. Numerical results suggest that reinfection of recovered individuals who have lost their protective immunity will create a large pool of asymptomatic infectious individuals which will ultimately increase symptomatic individuals with mild symptoms and symptomatic individuals with severe symptoms (critically ill) needing urgent medical attention. The model suggests that reinfection with COVID-19 will lead to an increase in cumulative reported deaths. Comparison of the impact of non pharmaceutical interventions on curbing COVID19 proliferation suggests that wearing face masks profoundly reduce COVID-19 prevalence than maintaining social/physical distance. Further, numerical findings reveal that increasing detection rate of asymptomatic cases via contact tracing, testing and isolating them can drastically reduce COVID-19 surge, in particular individuals who are critically ill and require admission into intensive care.

Omicron (B.1.1.529) - variant of concern - molecular profile and epidemiology: a mini review.

Recently a new variant of SARS-CoV-2 was reported from South Africa. World Health Organization (WHO) named this mutant as a variant of concern - Omicron (B.1.1.529) on 26th November 2021. This variant exhibited more than thirty amino acid mutations in the spike protein. This mutation rate is exceeding the other variants by approximately 5-11 times in the receptor-binding motif of the spike protein. Omicron (B.1.1.529) variant might have enhanced transmissibility and immune evasion. This new variant can reinfect individuals previously infected with other SARS-CoV-2 variants. Scientists expressed their concern about the efficacy of already existing COVID-19 vaccines against Omicron (B.1.1.529) infections. Some of the crucial mutations that are detected in the receptor-binding domain of the Omicron variant have been shared by previously evolved SARS-CoV-2 variants. Based on the Omicron mutation profile in the receptor-binding domain and motif, it might have collectively enhanced or intermediary infectivity relative to its previous variants. Due to extensive mutations in the spike protein, the Omicron variant might evade the immunity in the vaccinated individuals.

A systematic review and meta-analysis on the rate of human schistosomiasis reinfection.

While praziquantel mass drug administration is currently the most widely used method in the control of human schistosomiasis, it does not prevent subsequent reinfection hence persistent transmission. Towards schistosomiasis elimination, understanding the reinfection rate is crucial in planning for the future interventions. However, there is scarcity of information on the global reinfection rate of schistosomiasis. This systematic review and meta-analysis aimed at summarizing studies that estimated the reinfection rate of human schistosomiasis. Three data bases (PubMed, Hinari and Google Scholar) were thoroughly searched to retrieve original research articles presenting data on reinfection rate of human schistosomiasis. Study quality and risk of bias was assessed based on Joanna Briggs Institute critical appraisal checklist. Meta-analysis was conducted using statistical R version 3.6.2 and R Studio using "meta" and "metafor" packages. Random effect model was employed to estimate pooled reinfection rates. Heterogeneity was determined using Cochran's Q (chi-square)-test and Higgins I2 statistics. A total of 29 studies met inclusion criteria to be included in this review. All studies had at least satisfactory (5-9 scores) quality. The overal mean and pooled reinfection rates of schistosomiasis were 36.1% (±23.3%) and 33.2% (95% CI, 26.5-40.5%) respectively. For intestinal schistosomiasis, the mean and pooled reinfection rates were 43.9% (±20.6%) and 43.4% (95% CI, 35.8-51.4%), and that for urogenital schistosomiasis were 17.6% (±10.8%) and 19.4% (95% CI, 12.3%- 29.2%) respectively. Cochran's Q (chi-square)-test and Higgins I2 statistic indicated significant heterogeneity across studies (p-values < 0.001, I2 values > 95%). Results of subgroup analysis showed that, the type of Schistosoma species, participants' age group, sample size and geographical area had influence on disparity variation in reinfection rate of schistosomiasis (p < 0.1). Despite the control measures in place, the re-infection rate is still high, specifically on intestinal schistosomiasis as compared to urogenital schistosomiasis. Achieving 2030 sustainable development goal 3 on good health and wellbeing intensive programmatic strategies for schistosomiasis elimination should be implemented. Among such strategies to be used at national level are repeated mass drug administration at least every six months, intensive snails control and health education.

Condition for Global Stability for a SEIR Model Incorporating Exogenous Reinfection and Primary Infection Mechanisms.

A mathematical model incorporating exogenous reinfection and primary progression infection processes is proposed. Global stability is examined using the geometric approach which involves the generalization of Poincare-Bendixson criterion for systems of n-ordinary differential equations. Analytical results show that for a Susceptible-Exposed-Infective-Recovered (SEIR) model incorporating exogenous reinfection and primary progression infection mechanisms, an additional condition is required to fulfill the Bendixson criterion for global stability. That is, the model is globally asymptotically stable whenever a parameter accounting for exogenous reinfection is less than the ratio of background mortality to effective contact rate. Numerical simulations are also presented to support theoretical findings.