Theoretical perspectives on central chemosensitivity: CO2/H+-sensitive neurons in the locus coeruleus.

Central chemoreceptors are highly sensitive neurons that respond to changes in pH and CO2 levels. An increase in CO2/H+ typically reflects a rise in the firing rate of these neurons, which stimulates an increase in ventilation. Here, we present an ionic current model that reproduces the basic electrophysiological activity of individual CO2/H+-sensitive neurons from the locus coeruleus (LC). We used this model to explore chemoreceptor discharge patterns in response to electrical and chemical stimuli. The modeled neurons showed both stimulus-evoked activity and spontaneous activity under physiological parameters. Neuronal responses to electrical and chemical stimulation showed specific firing patterns of spike frequency adaptation, postinhibitory rebound, and post-stimulation recovery. Conversely, the response to chemical stimulation alone (based on physiological CO2/H+ changes), in the absence of external depolarizing stimulation, showed no signs of postinhibitory rebound or post-stimulation recovery, and no depolarizing sag. A sensitivity analysis for the firing-rate response to the different stimuli revealed that the contribution of an applied stimulus current exceeded that of the chemical signals. The firing-rate response increased indefinitely with injected depolarizing current, but reached saturation with chemical stimuli. Our computational model reproduced the regular pacemaker-like spiking pattern, action potential shape, and most of the membrane properties that characterize CO2/H+-sensitive neurons from the locus coeruleus. This validates the model and highlights its potential as a tool for studying the cellular mechanisms underlying the altered central chemosensitivity present in a variety of disorders such as sudden infant death syndrome, depression, and anxiety. In addition, the model results suggest that small external electrical signals play a greater role in determining the chemosensitive response to changes in CO2/H+ than previously thought. This highlights the importance of considering electrical synaptic transmission in studies of intrinsic chemosensitivity.

Entomological characterization of Aedes mosquitoes and arbovirus detection in Ibagué, a Colombian city with co-circulation of Zika, dengue and chikungunya viruses.

BACKGROUND: Dengue, Zika and chikungunya are arboviruses of significant public health importance that are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. In Colombia, where dengue is hyperendemic, and where chikungunya and Zika were introduced in the last decade, more than half of the population lives in areas at risk. The objective of this study was to characterize Aedes spp. vectors and study their natural infection with dengue, Zika and chikungunya in Ibagué, a Colombian city and capital of the department of Tolima, with case reports of simultaneous circulation of these three arboviruses. METHODS: Mosquito collections were carried out monthly between June 2018 and May 2019 in neighborhoods with different levels of socioeconomic status. We used the non-parametric Friedman, Mann-Whitney and Kruskal-Wallis tests to compare mosquito density distributions. We applied logistic regression analyses to identify associations between mosquito density and absence/presence of breeding sites, and the Spearman correlation coefficient to analyze the possible relationship between climatic variables and mosquito density. RESULTS: We collected Ae. aegypti in all sampled neighborhoods and found for the first time Ae. albopictus in the city of Ibagué. A greater abundance of mosquitoes was collected in neighborhoods displaying low compared to high socioeconomic status as well as in the intradomicile compared to the peridomestic space. Female mosquitoes predominated over males, and most of the test females had fed on human blood. In total, four Ae. aegypti pools (3%) were positive for dengue virus (serotype 1) and one pool for chikungunya virus (0.8%). Interestingly, infected females were only collected in neighborhoods of low socioeconomic status, and mostly in the intradomicile space. CONCLUSIONS: We confirmed the co-circulation of dengue (serotype 1) and chikungunya viruses in the Ae. aegypti population in Ibagué. However, Zika virus was not detected in any mosquito sample, 3 years after its introduction into the country. The positivity for dengue and chikungunya viruses, predominance of mosquitoes in the intradomicile space and the high proportion of females fed on humans highlight the high risk for arbovirus transmission in Ibagué, but may also provide an opportunity for establishing effective control strategies.

Geometrical analysis of bursting pacemaker neurons generated by computational models: comparison to in vitro pre-Bötzinger complex bursting neurons.

Despite an incredible amount of progress toward understanding respiratory rhythm generation through the use of reduced mathematical models, controversy exists concerning the role of various ionic conductances in generating bursting behavior. Moreover, the dynamical behavior of these model neurons has not been examined. Here, we have used two well described pre-Bötzinger complex (pre-BötC) pacemaker neuron models to investigate their dynamical features. Based on our observations, we identify one of the models to better represent the general characteristics of the bursting dynamics and propose additional modifications to better capture the dynamics of our own experimental recordings.

Estimating snakebite incidence from mathematical models: A test in Costa Rica.

BACKGROUND: Snakebite envenoming is a neglected public health challenge that affects mostly economically deprived communities who inhabit tropical regions. In these regions, snakebite incidence data is not always reliable, and access to health care is scare and heterogeneous. Thus, addressing the problem of snakebite effectively requires an understanding of how spatial heterogeneity in snakebite is associated with human demographics and snakes' distribution. Here, we use a mathematical model to address the determinants of spatial heterogeneity in snakebite and we estimate snakebite incidence in a tropical country such as Costa Rica. METHODS AND FINDINGS: We combined a mathematical model that follows the law of mass action, where the incidence is proportional to the exposed human population and the venomous snake population, with a spatiotemporal dataset of snakebite incidence (Data from year 1990 to 2007 for 193 districts) in Costa Rica. This country harbors one of the most dangerous venomous snakes, which is the Terciopelo (Bothrops asper, Garman, 1884). We estimated B. asper distribution using a maximum entropy algorithm, and its abundance was estimated based on field data. Then, the model was adjusted to the data using a lineal regression with the reported incidence. We found a significant positive correlation (R2 = 0.66, p-value < 0.01) between our estimation and the reported incidence, suggesting the model has a good performance in estimating snakebite incidence. CONCLUSIONS: Our model underscores the importance of the synergistic effect of exposed population size and snake abundance on snakebite incidence. By combining information from venomous snakes' natural history with census data from rural populations, we were able to estimate snakebite incidence in Costa Rica. The model was able to fit the incidence data at fine administrative scale (district level), which is fundamental for the implementation and planning of management strategies oriented to reduce snakebite burden.

A mathematical model of pH(i) regulation in central CO2- chemoreception.

In CO2 chemosensitive neurons, an increase in CO2 (hypercapnia) leads to a maintained reduction in intracellular pH (pH(i)) while in non-chemosensitive neurons pH(i) recovery is observed. The precise mechanisms for the differential regulation of pH(i) recovery between these cell populations remain to be identified; however, studies have begun to explore the role of Na+/H+ exchange (NHE). Here, we compare the results of two different formulations of a mathematical model to begin to explore pH(i) regulation in central CO2 chemoreception.

The impact of landscape transformation on the reinfestation rates of Rhodnius prolixus in the Orinoco Region, Colombia.

Trypanosoma cruzi, the agent responsible for Chagas disease, is widely distributed in the Americas in association to insect vectors and animal reservoirs. Triatomines are common vectors of Chagas disease and they vary in their distribution and affinity to human or sylvatic environments. Thus, control programs that include house spraying have been successful in regions were insects have a tendency to domiciliation. In the Orinoco region of Colombia, Rhodnius prolixus is the main vector presenting a stable sylvatic cycle, but is also found colonizing human dwellings. In 1997, health authorities developed a control program in the Department of Casanare spreading with insecticide houses in 667 localities. Infestation Indexes (I.I.) were calculated at the locality level before and after spraying. Times for re-infestation assessment varied between 1 and 67 months. Localities were classified into 3 groups according to their I.I. after spraying. Group 1 dropped their I.I. down to zero, Group 2 had a drop but remained positive and Group 3 increased its I.I. after spraying. We classified each group in terms of their land use characteristics before and after spraying based on satellite images obtained for the years 1997 (beginning of the study) and 2002 (end of program). We found that spraying significantly reduce the I.I. on average. However, we found that time after spraying does not produce significant differences in the I.I. Interestingly, land use changes and variations on I.I. after spraying for all groups were significantly dependent.

Environmental changes can produce shifts in chagas disease infection risk.

An epidemiological network contains all the organisms involved (types) in the transmission of a parasite. The nodes of the network represent reservoirs, hosts, and vectors, while the links between the nodes represent the strength and direction of parasite movement. Networks that contain humans are of special interest because they are of concern to public health authorities. Under these circumstances, it is possible, in principle, to identify cycles (closed paths in the network) that include humans and select the ones that carry the maximum probability of human infection. The basic reproduction number R 0 in such a network gives the average number of new infections of any type after the introduction of one individual infected by any type. To obtain R 0 for complex networks, one can use the next-generation matrix (NGM) approach. Every entry in NGM will average the contribution of each link that connects two types. To tease the contribution of every cycle apart, we define the virulence as the geometric mean of the NGM entries corresponding to the links therein. This approach allows for the quantification of specific cycles of interest while it also makes the computation of the sensitivity and elasticity of the parameters easier. In this work, we compute the virulence for the transmission dynamics of Chagas disease for a typical rural area in Colombia incorporating the effect of environmental changes on the vector population size. We concluded that the highest contribution to human infection comes from humans themselves, which is a surprising and interesting result. In addition, sensitivity analysis revealed that increasing vector population size increases the risk of human infection.

Using the basic reproduction number to assess the effects of climate change in the risk of Chagas disease transmission in Colombia.

The dynamics of vector-borne diseases has often been linked to climate change. However the commonly complex dynamics of vector-borne diseases make it very difficult to predict risk based on vector or host distributions. The basic reproduction number (R0) integrates all factors that determine whether a pathogen can establish or not. To obtain R0 for complex vector-borne diseases one can use the next-generation matrix (NGM) approach. We used the NGM to compute R0 for Chagas disease in Colombia incorporating the effect of temperature in some of the transmission routes of Trypanosoma cruzi. We used R0 to generate a risk map of present conditions and a forecast risk map at 20 years from now based on mean annual temperature (data obtained from Worldclim). In addition we used the model to compute elasticity and sensitivity indexes on all model parameters and routes of transmission. We present this work as an approach to indicate which transmission pathways are more critical for disease transmission but acknowledge the fact that results and projections strongly depend on better knowledge of entomological parameters and transmission routes. We concluded that the highest contribution to R0 comes from transmission of the parasites from humans to vectors, which is a surprising result. In addition,parameters related to contacts between human and vectors and the efficiency of parasite transmission between them also show a prominent effect on R0.

Differences in pHi recovery in CO2-chemosensitive and non-chemosensitive cells: predictions from a mathematical model.

In this paper, we present a mathematic model designed to identify potential mechanisms responsible for the observed differences in pHi recovery in CO(2)-chemosensitive versus non-chemosensitive cells. The model suggests that differences in pHi regulation may be dependent upon differences in the activation set-point of the internal modifier site of the Na(+)/H(+) exchanger (NHE).

Morbilidad de la enfermedad de Chagas en fase cronica en Colombia. Deteccion de pacientes chagasicos con cardiopatia en un area endemica del departamento de Boyaca / Morbidity of Chagas's disease in chronic phase on Colombia

Introducción: en Colombia se estima que existen 1.200.000 personas infectadas con T. cruzi. Los estudios publicados sobre cardiomiopatía chagásica en Colombia han sido usualmente descritos en hospitales de tercer nivel. Objetivo: caracterizar desde el punto de vista clínico y electrocardiográfico la cardiomiopatía chagásica crónica en centros de atención primaria en un área endémica. Diseño del estudio: estudio descriptivo, seccional de morbilidad en población chagásica y no chagásica no seleccionadas. Lugar del estudio: municipios de San Eduardo, Zetaquira y Campohermoso, Boyacá. Pacientes: 405 individuos. Mediciones: se consideraron: edad, sexo, escolaridad, antecedentes, síntomas y signos físicos y hallazgos electrocardiográfícos. Se practicaron serologías por test de ELISA e IFI. Se estableció como seropositivo aquel paciente con positividad en las dos pruebas y seronegativo aquél con resultado negativo en las dos técnicas. Análisis estadístico: se calcularon promedios y proporciones de las distintas variables para los dos grupos de acuerdo con el nivel de medición y se establecieron las diferencias de proporciones entre ellos, tomando un nivel de significación del 0.5 por ciento. Resultados: 405 individuos, 205 seropositivos y 200 seronegativos (control). Edad promedio 45 años, 58 por ciento del sexo femenino para ambos grupos. El 80 por ciento del total de los dos grupos no alcanzó un nivel de escolaridad mayor al de primaria completa. Los hallazgos significativos a favor del grupo de seropositivos fueron: contacto con triatominios (p.-O.OOOl), Chagas en hermanos (p :0.01), muerte súbita en hermanos (p:0.04), sensación de palpitaciones (p:0.05), presíncope (p:0.005), angina (p:0.03), insuficiencia mitral (p:0.004), bloqueo de rama derecha (p:0.01), bloqueo bifascicular (p :0.007) y trastornos de la repolarización (p;0.008). Conclusiones: los hallazgos observados en el grupo de pacientes seropositivos con diagnóstico de cardiomiopatía de Chagas, corresponden a estadios clínicos I y II de la enfermedad. La edad media, el predominio en el sexo femenino, el pobre nivel de escolaridad, los antecedentes personales y familiares, son de resaltar por su impacto socio-económico