C4b-binding protein (C4BP) is an important plasma inhibitor of the classical pathway of complement activation. Several bacterial pathogens bind C4BP, which may contribute to their virulence. In the present report we demonstrate that isolated type IV pili from Neisseria gonorrhoeae bind human C4BP in a dose-dependent and saturable manner. C4BP consists of seven identical α-chains and one β-chain linked together with disulfide bridges. We found that pili bind to the α-chain of C4BP, which is composed of eight homologous complement control protein (CCP) domains. From the results of an inhibition assay with C4b and a competition assay in which we tested mutants of C4BP lacking individual CCPs, we concluded that the binding area for pili is localized to CCP1 and CCP2 of the α-chain. The binding between pili and C4BP was abolished at 0.25 M NaCl, implying that it is based mostly on ionic interactions, similarly to what have been observed for C4b-C4BP binding. Furthermore, the N-terminal part of PilC, a structural component of pili, appeared to be responsible for binding of C4BP. Membrane cofactor protein, previously shown to be a receptor for pathogenic N. gonorrhoeae on the surface of epithelial cells, competed with C4BP for binding to pili only at high concentrations, suggesting that different parts of pili are involved in these two interactions. Accordingly, high concentrations of C4BP were required to inhibit binding of N. gonorrhoeae to Chang conjunctiva cells, and no inhibition of binding was observed with cervical epithelial cells.

Climate has been an important factor in shaping the distribution and incidence of dengue cases in tropical and subtropical countries. In Costa Rica, a tropical country with distinctive micro-climates, dengue has been endemic since its introduction in 1993, inflicting substantial economic, social, and public health repercussions. Using the number of dengue reported cases and climate data from 2007-2017, we fitted a prediction model applying a Generalized Additive Model (GAM) and Random Forest (RF) approach, which allowed us to retrospectively predict the relative risk of dengue in five climatological diverse municipalities around the country.In Costa Rica, as in most of the Americas, the reintroduction and dissemination of Aedes aegypti took place during the 1970s [19,52]. However, it was until September 1993 that the first dengue cases were reported on the Pacific coast [43] when autochthonous transmission of DENV-1 was confirmed [47]. Since then, three of the four serotypes of the virus (DENV-1, DENV-2, DENV-3) have circulated the national territory, with peaks of transmission that exhibit both seasonal and inter-annual variability [43]. Over 370,000 suspected and confirmed cases have been reported by the Ministry of Health [43], of which, more than 45,000 have required hospital care [10].With the high burden that DENV infections represent to the country, where, as in most endemic regions, traditional control measures have proven ineffective to sustain long-term trends in cases-reduction [21], surveillance, prevention, and control of dengue is a public health challenge that requires specific and cost-effective strategies [65]. In this effort, and as a worldwide strategy for reducing dengue incidence, the World Health Organization (WHO) is highlighting the importance of determining sensitive indicators for dengue outbreaks as early warning signals [65], in which climate and weather variables have shown to play an essential role [31,18,20]. Specifically, variables such as temperature, precipitation, humidity and El Niño Southern Oscillation (ENSO), have been closely correlated to the occurrence of dengue cases and the seasonality of dengue epidemics [16,12,69].Changes in these climate conditions influence the ecology of the DENV by modulating vector mosquito population dynamics, viral replication, and transmission, as well as, human behavior [7,48]. It has been observed that transmission of DENV occurs between 18 • C -34 • C, with maximal transmission peaks in the range of 26 • C -29 • C [46]. At higher temperatures, the duration of the life cycle decreases [72,60], biting activity increases [62,55,20] and the extrinsic incubation period becomes shorter [15,70], prolonging the infective days of the mosquito [20]. Precipitation provides habitat for the aquatic stages of the life cycle and influences vector distribution [48]. Moreover, heavy rainfall events can decrease mosquito abundance by flushing larvae from containers [36,4], and drought events can increase household water containers [61]. Humidity also affects...

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For countries starting to receive steady supplies of vaccines against SARS-CoV-2, the course of Covid-19 for the following months will be determined by the emergence of new variants and successful roll-out of vaccination campaigns. To anticipate this scenario, we used a multilayer network model developed to forecast the transmission dynamics of Covid-19 in Costa Rica, and to estimate the impact of the introduction of the Delta variant in the country, under two plausible vaccination scenarios, one sustaining Costa Rica’s July 2021 vaccination pace of 30,000 doses per day and with high acceptance from the population and another with declining vaccination pace to 13,000 doses per day and with lower acceptance. Results suggest that the introduction and gradual dominance of the Delta variant would increase Covid-19 hospitalizations and ICU admissions by $$35\%$$ 35 % and $$33.25\%$$ 33.25 % , respectively, from August 2021 to December 2021, depending on vaccine administration and acceptance. In the presence of the Delta variant, new Covid-19 hospitalizations and ICU admissions are estimated to increase around $$24.26\%$$ 24.26 % and $$27.19\%$$ 27.19 % , respectively, in the same period if the vaccination pace drops. Our results can help decision-makers better prepare for the Covid-19 pandemic in the months to come.

The aim of this paper is to infer the effects that change on human mobility had on the transmission dynamics during the first four months of the SARS-CoV-2 pandemic in Costa Rica, which could have played a role in delaying community transmission in the country. First, by using parametric and non-parametric change-point detection techniques, we were able to identify two different periods when the trend of daily new cases significantly changed. Second, we explored the association of these changes with data on population mobility. This also allowed us to estimate the lag between changes in human mobility and rates of daily new cases. The information was then used to establish an association between changes in population mobility and the sanitary measures adopted during the study period. Results showed that during the initial two months of the pandemic in Costa Rica, the implementation of sanitary measures and their impact on reducing human mobility translated to a mean reduction of 54% in the number of daily cases from the projected number, delaying community transmission.