The Microbiome as Part of the Contemporary View of Tuberculosis Disease.

The study of the microbiome has changed our overall perspective on health and disease. Although studies of the lung microbiome have lagged behind those on the gastrointestinal microbiome, there is now evidence that the lung microbiome is a rich, dynamic ecosystem. Tuberculosis is one of the oldest human diseases, it is primarily a respiratory infectious disease caused by strains from the Mycobacterium tuberculosis Complex. Even today, during the COVID-19 pandemic, it remains one of the principal causes of morbidity and mortality worldwide. Tuberculosis disease manifests itself as a dynamic spectrum that ranges from asymptomatic latent infection to life-threatening active disease. The review aims to provide an overview of the microbiome in the tuberculosis setting, both in patients' and animal models. We discuss the relevance of the microbiome and its dysbiosis, and how, probably through its interaction with the immune system, it is a significant factor in tuberculosis's susceptibility, establishment, and severity.

Presence of invasive American bullfrogs may reduce infectious disease in a native frog species.

Amphibians breeding in aquatic environments may encounter a myriad of threats during their life cycle. One species known to prey on native amphibians in aquatic habitats is the invasive North American bullfrog Lithobates catesbeianus, which, besides being a voracious predator and competitor, often acts as a pathogen carrier and disease superspreader because it tolerates high infection loads of the frog-killing fungus Batrachochytrium dendrobatidis (Bd). Here, we hypothesized that the presence of the bullfrogs in microcosms should either (1) decrease Bd disease severity in native frog species by discouraging them from using the aquatic environment, or (2) increase the mortality of the native species. We tested these 2 mutually exclusive hypotheses by co-housing the snouted treefrog Scinax x-signatus (native to our study area) with L. catesbeianus in the laboratory, exposing them to Bd, and using qPCR analysis to quantify the resulting Bd infection loads in the native frogs. Our experiment had the following replicated treatments: (1) native-only treatment (3 individuals of S. x-signatus), (2) native-predominant treatment (2 S. x-signatus + 1 L. catesbeianus), and (3) exotic-predominant treatment (1 S. x-signatus + 2 L. catesbeianus). We found that Bd infection loads in the native S. x-signatus were highest in the native-only treatment, and lowest in the exotic-predominant treatment, indicating that bullfrogs may discourage native frogs from occupying the aquatic habitat, thus reducing encounter rates between native frogs and the waterborne pathogen. This effect could be driven by the bullfrogs' predatory behavior and their high philopatry to aquatic habitats. Our results highlight that predation risk adds to the complexity of host-species interactions in Bd epidemiology.

Nonlinear time-series forecasts for decision support: short-term demand for ICU beds in Santiago, Chile, during the 2021 COVID-19 pandemic.

In Chile, due to the explosive increase of new Coronavirus disease 2019 (COVID-19) cases during the first part of 2021, the ability of health services to accommodate new incoming cases was jeopardized. It has become necessary to be able to manage intensive care unit (ICU) capacity, and for this purpose, monitoring both the evolution of new cases and the demand for ICU beds has become urgent. This paper presents short-term forecast models for the number of new cases and the number of COVID-19 patients admitted to ICUs in the Metropolitan Region in Chile.

An SEIARD epidemic model for COVID-19 in Mexico: Mathematical analysis and state-level forecast.

We propose an SEIARD mathematical model to investigate the current outbreak of coronavirus disease (COVID-19) in Mexico. Our model incorporates the asymptomatic infected individuals, who represent the majority of the infected population (with symptoms or not) and could play an important role in spreading the virus without any knowledge. We calculate the basic reproduction number (R 0) via the next-generation matrix method and estimate the per day infection, death and recovery rates. The local stability of the disease-free equilibrium is established in terms of R 0. A sensibility analysis is performed to determine the relative importance of the model parameters to the disease transmission. We calibrate the parameters of the SEIARD model to the reported number of infected cases, fatalities and recovered cases for several states in Mexico by minimizing the sum of squared errors and attempt to forecast the evolution of the outbreak until November 2020.

Simple epidemic network model for highly heterogeneous populations.

Network models for disease transmission and dynamics are popular because they are among the simplest agent-based models. Highly heterogeneous populations (in the number of contacts) may be modeled by networks with long-tailed degree distributions for which the variance is much greater than the mean degree. An example is given by scale-free networks where the degree distribution follows a power law. In these type of networks there is not a typical degree. Some nodes may have low representation in the population but are key to drive disease transmission. Coarse graining may be used to simplify these complex networks. In this work we present a simple model consisting in of a network where nodes have only two possible degrees, a low degree close to the mean degree and a high degree about ten times the mean degree. We show that in spite of this extreme simplification, main features of disease dynamics in scale-free networks are well captured by our model.

Reservoir frogs: seasonality of Batrachochytrium dendrobatidis infection in robber frogs in Dominica and Montserrat.

Emerging infectious diseases are an increasingly important threat to wildlife conservation, with amphibian chytridiomycosis, caused by Batrachochytrium dendrobatidis, the disease most commonly associated with species declines and extinctions. However, some amphibians can be infected with B. dendrobatidis in the absence of disease and can act as reservoirs of the pathogen. We surveyed robber frogs (Eleutherodactylus spp.), potential B. dendrobatidis reservoir species, at three sites on Montserrat, 2011-2013, and on Dominica in 2014, to identify seasonal patterns in B. dendrobatidis infection prevalence and load (B. dendrobatidis genomic equivalents). On Montserrat there was significant seasonality in B. dendrobatidis prevalence and B. dendrobatidis load, both of which were correlated with temperature but not rainfall. B. dendrobatidis prevalence reached 35% in the cooler, drier months but was repeatedly undetectable during the warmer, wetter months. Also, B. dendrobatidis prevalence significantly decreased from 53.2% when the pathogen emerged on Montserrat in 2009 to a maximum 34.8% by 2011, after which it remained stable. On Dominica, where B. dendrobatidis emerged seven years prior to Montserrat, the same seasonal pattern was recorded but at lower prevalence, possibly indicating long-term decline. Understanding the dynamics of disease threats such as chytridiomycosis is key to planning conservation measures. For example, reintroductions of chytridiomycosis-threatened species could be timed to coincide with periods of low B. dendrobatidis infection risk, increasing potential for reintroduction success.

The drivers and consequences of unstable Plasmodium dynamics: a long-term study of three malaria parasite species infecting a tropical lizard.

Understanding the consequences of environmental fluctuations for parasite dynamics requires a long-term view stretching over many transmission cycles. Here we studied the dynamics of three malaria parasites (Plasmodium azurophilum, P. leucocytica and P. floridense) infecting the lizard Anolis gundlachi, in the rainforest of Puerto Rico. In this malaria-anole system we evaluated temporal fluctuations in individual probability of infection, the environmental drivers of observed variation and consequences for host body condition and Plasmodium parasites assemblage. We conducted a total of 15 surveys including 10 from 1990 to 2002 and five from 2015 to 2017. During the early years, a lizard's probability of infection by all Plasmodium species appeared stable despite disturbances ranging from two hurricanes to short droughts. Over a longer timescale, probability of infection and overall prevalence varied significantly, following non-linear relationships with temperature and rainfall such that highest prevalence is expected at intermediate climate measures. A perplexing result was that host body condition was maximized at intermediate levels of rainfall and/or temperature (when risk of infection was highest), yet we found no significant decreases in body condition due to infection. Plasmodium parasite species composition varied through time with a reduction and near local extinction of P. floridense. Our results emphasize the need for long-term studies to reveal host-parasite dynamics, their drivers and consequences.

Mathematical modelling for Zoonotic Visceral Leishmaniasis dynamics: A new analysis considering updated parameters and notified human Brazilian data.

Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis: according to the Brazilian Ministry of Health, the annual number of new human cases and deaths due to this disease has been increasing for the last 20 years. In addition, regarding the Americas, the specific relationship between canine and human for Visceral Leishmaniasis dynamics is still not well understood. In this work we propose a new model for Zoonotic Visceral Leishmaniasis, based on the models previously published by Burattini et al. (1998) and Ribas et al. (2013). Herein, we modeled the disease dynamics using a modified set of differential equations from those two authors, considering the same assumptions (inclusion of human, dog and sandfly populations, all constants over time). From this set of equations we were able to calculate the basic reproduction number R0 and to analyze the stability and sensitivity of the system to the parameters variability. As main result, when the stability of the system is reached, the normalized reporting human cases rate is estimated in 9.12E-08/day. This estimation is very close to the 2015 report from Araçatuba city, 5.69E-08/day. We also observed from stability and sensitivity analysis that the activity of sandfly population is critical to introduction and maintenance of Zoonotic Visceral Leishmaniasis in the population. In addition, the importance of dog as source of infection concentrates on latent dog, since it does not show clinical symptoms and signs and, therefore, has a great contribution to disease dissemination. As conclusion, considering the presently ethical issues regarding to elimination of positive dog in Brazil and the highly sensitivity of disease dynamics on sandfly population, we recommend that the sandfly population control should be prioritized.