An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India

Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions.

COVID-19 endgame: from pandemic to endemic? Vaccination, reopening and evolution in a well-vaccinated population

COVID-19 remains a major public health concern, with large resurgences even where there has been widespread uptake of vaccines. Waning immunity and the emergence of new variants will shape the long-term burden and dynamics of COVID-19. We explore the transition to the endemic state, and the endemic incidence, using a combination of modelling approaches. We compare gradual and rapid reopening and reopening at different vaccination levels. We examine how the eventual endemic state depends on the duration of immunity, the rate of importations, the efficacy of vaccines and the transmissibility. These depend on the evolution of the virus, which continues to undergo selection. Slower reopening leads to a lower peak level of incidence and fewer overall infections: as much as a 60% lower peak and a 10% lower total in some illustrative simulations; under realistic parameters, reopening when 70% of the population is vaccinated leads to a large resurgence in cases. The long-term endemic behaviour may stabilize as late as January 2023, with further waves of high incidence occurring depending on the transmissibility of the prevalent variant, duration of immunity, and antigenic drift. We find that long term endemic levels are not necessarily lower than current pandemic levels: in a population of 100,000 with representative parameter settings (Reproduction number 5, 1-year duration of immunity, vaccine efficacy at 80% and importations at 3 cases per 100K per day) there are over 100 daily incident cases in the model. The consequent burden on health care systems depends on the severity of infection in immunized or previously infected individuals.

The analysis of hepatitis B virus (HBV) transmission using an epidemic model

In this article, we propose an epidemic problem of hepatitis B with vaccination. So to do this, first we presents the model formulation and prove that the solutions are bounded and positive. We obtain the disease free equilibrium and calculate the basic reproduction number (R0). The reproductive number will be used to find the endemic state of the model. We discuss the qualitative analysis of the proposed problem and show that whenever, R0 < 1 then the disease free equilibrium is stable locally and globally. Moreover, whenever, R0 > 1, then the endemic state is asymptotically stable. We derive sufficient conditions for both the equilibria and its stabilities. Further more numerical simulation are carried out to illustrate the feasibility of the obtained results and verified that with actual data, we are in the position to put down the hepatitis B infection form the community. We also highlight the role of epidemic parameters in the disease propagation. Our numerical works verified the analytical results. Finally some important conclusion are given at the end of the article.

Stochastic social behavior coupled to COVID-19 dynamics leads to waves, plateaus and an endemic state

It is well recognized that population heterogeneity plays an important role in the spread of epidemics. While individual variations in social activity are often assumed to be persistent, i.e. constant in time, here we discuss the consequences of dynamic heterogeneity. By integrating the stochastic dynamics of social activity into traditional epidemiological models we demonstrate the emergence of a new long timescale governing the epidemic, in broad agreement with empirical data. Our Stochastic Social Activity model captures multiple features of real-life epidemics such as COVID-19, including prolonged plateaus and multiple waves, which are transiently suppressed due to the dynamic nature of social activity. The existence of a long timescale due to the interplay between epidemic and social dynamics provides a unifying picture of how a fast-paced epidemic typically will transition to an endemic state.

Living with COVID-19: The road ahead

ABSTRACT Introduction: The COVID-19 pandemic has affected the world for more than a year, with multiple waves of infections resulting in morbidity, mortality and disruption to the economy and society. Response measures employed to control it have generally been effective but are unlikely to be sustainable over the long term. Methods: We examined the evidence for a vaccine-driven COVID-19 exit strategy including academic papers, governmental reports and epidemiological data, and discuss the shift from the current pandemic footing to an endemic approach similar to influenza and other re spiratory infectious diseases. Results: A desired endemic state is characterised by a baseline prevalence of infections with a generally mild disease profile that can be sustainably managed by the healthcare system, together with the resumption of near normalcy in human activities. Such an endemic state is attainable for COVID-19 given the promising data around vaccine efficacy, although uncertainty remains around vaccine immunity escape in emergent variants of concern. Maintenance of non-pharmaceutical interventions remains crucial until high vaccination coverage is attained to avoid runaway outbreaks. It may also be worthwhile to de-escalate measures in phases, before standing down most measures for an endemic state. If a variant that substantially evades immunity emerges, it will need to be managed akin to a new disease threat, with pandemic preparedness and response plans. Conclusion: An endemic state for COVID-19, characterised by sustainable disease control measures, is likely attainable through vaccination. Keywords: COVID-19, endemic, non-pharmaceutical interventions, transition, vaccination

Severity of SARS-CoV-2 reinfections in second wave determines likelihood of mild endemicity

Immunity to SARS-CoV-2 is building up globally, but will this be sufficient to prevent future COVID-19 epidemics in the face of variants and waning immunity? Manaus, Brazil offers a concerning glimpse of what may come: six months after the majority of the city's population experienced primary infection, a second wave with a new strain resulted in more deaths than the first wave. Current hypotheses for this surge rely on prior immunity waning due to time and antigenic distance. Here we show this hypothesis predicts a severe endemic state. We propose an alternative hypothesis in which individuals infected in the first wave lose protection against transmission but retain immunity against severe disease and show this hypothesis is equally compatible with existing data. In this scenario, the increased number of deaths is due to an increased infection fatality ratio (IFR) for primary infections with the new variant. This alternative predicts a mild endemic state will be reached within decades. Collecting data on the severity of reinfections and infections post-vaccination as a function of time and antigenic distance from the original exposure is crucial for optimizing control strategies.

Plausible Transition of Covid-19 from Pandemic to an Endemic State: Impact of Variant UK Strain, b 7.1.1, on the Spread of Covid-19 in the Population

Covid-19 is a contagious disease spreading without showing any signs of abatement across the world. Presently, sars-cov-2, the causative agent of covid-19, is giving a fresh threatening signs to renew its devastation as several new mutated strains have been detected in United Kingdom, south africa, brazil & the usa; the first variant being detected in the united kingdom (b 7.1.1). Here we have shown that there was a gradual waning of active cases of covid-19 (strain originated in wuhan, china) across the nation after implementation of complete lockdown; this demonstrated that covid-19 had lost its sheen and the covid-19 pandemic was nearing an end. However, the recent emergence of the mutated forms of sars-cov-2 in different countries including India, appears to be more contagious and virulent than the original form. This property of the variant strain could affect the ongoing pandemic. The implication of all the data obtained from the old and the new UK variant, b7.1.1, in context of pandemic has been discussed in this article.

Appetite and weight inducing and inhibiting neuroendocrine factors in Prader-Willi syndrome, Bardet-Biedl syndrome and craniopharyngioma versus anorexia nervosa

Obesity is reaching endemic state and has a major impact on health and economy. In most cases obesity is caused by life style factors. However, the risk of becoming obese differs highly between people. Individual differences in life style, genetic, and neuroendocrine factors play a role in satiety, hunger and regulation of body weight. In a small percentage of children and adults with obesity, an underlying hormonal or genetic cause can be found. The aim of this review is to present and compare data on the extreme ends of the obesity and undernutrition spectrum in patients with Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), acquired hypothalamic obesity in craniopharyngioma patients, and anorexia nervosa. This may give more insight in the role of neuroendocrine factors and might give direction for future research in conditions of severe obesity and underweight.

On the effect of postponing pregnancy in a Zika transmission model

We construct a Zika transmission model to investigate the effect of postponing pregnancy on the infection intensity. We perform analytical and numerical investigations for deterministic and stochastic analysis to obtain the basic reproductive ratio, endemic state, probability of disease extinction, and the probability of outbreak. The results indicate that by reducing the pregnancy rate the mosquito-to-human ratio increases, and, consequently, the basic reproductive ratio increases. Simultaneously, the probability of disease extinction decreases, and the probability of disease outbreak increases. On the other hand, the endemic state of infected infants initially increases with the decrease of the pregnancy recruitment rate, up to a certain level, and decreases as the recruitment rate of pregnancy tends to zero. This work highlights that postponing pregnancy that gives the individual temporary protection for unexpected infected newborns may increase the population infectivity.

Stochastic social behavior coupled to COVID-19 dynamics leads to waves, plateaus and an endemic state

It is well recognized that population heterogeneity plays an important role in the spread of epidemics. While individual variations in social activity are often assumed to be persistent, i.e. constant in time, here we discuss the consequences of dynamic heterogeneity. By integrating the stochastic dynamics of social activity into traditional epidemiological models we demonstrate the emergence of a new long timescale governing the epidemic in broad agreement with empirical data. Our model captures multiple features of real-life epidemics such as COVID-19, including prolonged plateaus and multiple waves, which are transiently suppressed due to the dynamic nature of social activity. The existence of the long timescale due to the interplay between epidemic and social dynamics provides a unifying picture of how a fast-paced epidemic typically will transition to the endemic state.