Trends in diabetes mortality identified from death certificates in Colombia, 1979-2017.

OBJECTIVE: To describe the mortality trends of diabetes mellitus (DM) in Colombia, by sex and age group, from 1979 to 2017. METHODS: We carried out an ecological study using mortality data from the Colombian National Administrative Department of Statistics. Crude and age-standardized annual mortality rates per 100 000 people were estimated. Trends of standardized rates were described by sex and age groups. Joinpoint regression models were performed to study mortality trends. RESULTS: Throughout the whole period, the total number of DM recorded deaths in Colombia was 200 650, 58% (116 316) in women (p<0.05). The age-standardized mortality rates (ASMR) by sex increased from 13.2 to 26.6 deaths per 100 000 in women and from 10.1 to 22.7 in men from 1979 to 1999. We observed a decrease from 26.6 to 15.4 per 100 000 in women, and from 22.7 to 15.9 in men for the period 1999-2017. The joinpoint regression analysis showed that the average annual percentage change of the period did not vary in both sexes (men: -0.2%, 95% CI -1.0 to 1.4%; women: 0.7%, 95% CI -0.1 to 1.6%). CONCLUSIONS: The DM mortality showed a decreasing trend after 2000 in women and 2004 in men. Primary and secondary prevention programs must continue to be strengthened for an earlier diagnosis of diabetes.

OBJETIVO: Describir las tendencias de la mortalidad por diabetes mellitus (DM) en Colombia, por sexo y grupo de edad, entre 1979 y 2017. MÉTODOS: Estudio ecológico con datos de mortalidad del Departamento Administrativo Nacional de Estadística de Colombia. Se estimaron las tasas de mortalidad anuales brutas y ajustadas por edad por cada 100 000 personas. Se describieron las tendencias de las tasas ajustadas por sexo y grupos de edad. Se realizaron modelos de regresión joinpoint para estudiar las tendencias de la mortalidad. RESULTADOS: En el período del estudio, el número total de muertes por DM registradas en Colombia fue de 200 650, el 58% (116 316) en mujeres (p<0,05). Las tasas de mortalidad ajustadas por edad, en cada sexo, aumentaron de 13,2 a 26,6 muertes por 100 000 en las mujeres y de 10,1 a 22,7 en los hombres entre 1979 y 1999. En el período 1999-2017 se observó una disminución de 26,6 a 15,4 por 100 000 en las mujeres y de 22,7 a 15,9 en los hombres. El análisis de regresión joinpoint demostró que el cambio porcentual anual medio del período no varió en ambos sexos (hombres: ­0,2%, IC 95% ­1,0 a 1,4%; mujeres: 0,7%, IC 95% ­0,1 a 1,6%). CONCLUSIONES: La mortalidad por DM mostró una tendencia decreciente después del año 2000 en las mujeres y del 2004 en los hombres. Es necesario seguir fortaleciendo los programas de prevención primaria y secundaria a fin de alcanzar un diagnóstico más temprano de la diabetes.

Maternal mortality in Colombia during the COVID-19 pandemic: time series and social inequities.

OBJECTIVE: The impact of the COVID-19 pandemic goes beyond morbidity and mortality from that disease. Increases in maternal mortality have also been described but have not been extensively studied to date. This study aimed to examine changes in maternal mortality and identify correlates and predictors of excess maternal mortality in Colombia during the pandemic. SETTING: Analysis of data from the national epidemiological surveillance databases of Colombia (Sivigila). PARTICIPANTS: Deaths among 6342 Colombian pregnant women who experienced complications associated with pregnancy, childbirth or the perperium during 2008-2020 were included in this study. For inequalities analysis, a subsample of 1055 women from this group who died in 2019 or 2020 years were analysed. METHODS: We collected data from the national surveillance system (Sivigila) on maternal mortality. Analysis was carried out in two stages, starting with a time series modelling using the Box-Jenkins approach. Data from Sivigila for 2008-2019 were used to establish a baseline of expected mortality levels. Both simple and complex inequality metrics, with the maternal mortality ratios (MMRs), were then calculated using the Multidimensional Poverty Index as a socioeconomic proxy. RESULTS: Maternal deaths in 2020 were 12.6% (95% CI -21.4% to 95.7%) higher than expected. These excess deaths were statistically significant in elevation for the months of July (97.4%, 95% CI 35.1% to 250.0%) and August (87.8%, 95% CI 30.5% to 220.8%). The MMR was nearly three times higher in the poorest municipalities compared with the most affluent communities in 2020. CONCLUSIONS: The COVID-19 pandemic had considerable impact on maternal health, not only by leading to increased deaths, but also by increasing social health inequity. Barriers to access and usage of essential health services are a challenge to achieving health-related Sustainable Development Goals.

Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis.

The cell surface of Candida albicans is enriched with highly glycosylated mannoproteins that are involved in the interaction with host tissues. N- and O-glycosylation are post-translational modifications that initiate in the endoplasmic reticulum, and finalize in the Golgi. The KRE2/MNT1 family encode a set of multifunctional mannosyltransferases that participate in O-, N- and phosphomannosylation. In order to gain insights into the substrate specificities of these enzymes, recombinant forms of Mnt1, Mnt2, and Mnt5 were expressed in Pichia pastoris and the enzyme activities characterized. Mnt1 and Mnt2 showed a high specificity for α-methylmannoside and α1,2-mannobiose as acceptor substrates. Notably, they also used Saccharomyces cerevisiaeO-mannans as acceptors and generated products with more than three mannose residues, suggesting than Mnt1 and Mnt2 could be the mannosyltransferases adding the fourth and fifth mannose residue to the O-mannans in C. albicans. Mnt5 only recognized α-methylmannoside as acceptor, suggesting that participates in the addition of the second mannose residues to the N-glycan outer chain.

Economic costs of severe seasonal influenza in Colombia, 2017-2019: A multi-center analysis.

OBJECTIVE: To estimate the economic burden of Severe Acute Respiratory Infection (SARI) in lab-confirmed influenza patients from a low-income country setting such as Colombia. METHODS: A bottom-up costing analysis, from both third payer and social perspectives, was conducted. Direct costs of care were based on the review of 227 clinical records of lab-confirmed influenza inpatients in six facilities from three main Colombian cities. Resources were categorized as: length of stay (LOS), diagnostic and laboratory tests, medications, consultation, procedures, and supplies. A survey was designed to estimate out-of-pocket expenses (OOPE) and indirect costs covered by patients and their families. Cost per patient was estimated with the frequency of use and prices of activities, calculating median and 95% confidence intervals (95% CI) with bootstrapping. Total costs are expressed as the sum of direct medical costs, OOPE and indirect costs in 2018 US dollars. RESULTS: The media direct medical cost per SARI lab-confirmed influenza patient was US$ 700 (95% CI US$ 552-809). Diagnostic and laboratory tests correspond to the highest cost per patient (37%). Median OOPE and indirect costs per patient was US$ 147 (95% CI US$ 94-202), with the highest costs for caregiver expenses (27%). Total costs were US$ 848 (95% CI US$ 646-1,011), OOPE and indirect costs corresponded to 17.4% of the total. The median of direct medical costs per patient was three times higher in elderly patients. CONCLUSION: SARI influenza costs impose a high economic burden on patients and their families. The results highlight the importance of strengthening preventive strategies nationwide in the age groups with higher occurrence and incurred health costs.

How Expensive Are Hospitalizations by COVID-19? Evidence From Colombia.

OBJECTIVES: This study aimed to estimate the direct medical costs due to hospitalizations by COVID-19 in Colombia and to identify their cost drivers in Colombia. METHODS: This is a retrospective cost-of-illness study of COVID-19 in Colombia. We estimated direct medical costs using data from patients insured to a Benefit Plan Administrator Company, between March 15, 2020 and May 29, 2020. Absolute and relative frequencies, averages, medians, and interquartile ranges (IQRs) were used to characterize the population and estimate the costs of hospitalized patients with COVID-19. We stratified the cost analysis by sex, age groups, comorbidities, and type of hospitalization (general ward and intensive care unit [ICU]). Cost drivers were calculated from a generalized linear model. RESULTS: We studied 113 confirmed patients, 51.3% men. On average, the hospital length of stay was 7.3 (± 6.2) days. A person hospitalized with COVID-19 reported median costs of $1688 (IQR 788-2523). In women, this cost was $1328 (IQR 463-2098); in men, this was 1.4 times greater. The median cost for ICU was $4118 (IQR 2069-5455), 3 times higher than those hospitalized only in the general ward. Admission to the ICU, having 1 comorbidity, length of stay, high blood pressure, having 5 comorbidities, and being treated in the city of Cartagena were statistically significant with direct medical costs. CONCLUSIONS: Our study provides an idea of the magnitude of costs needed to hospitalize a COVID-19 case in Colombia. Other studies in Colombia have assessed the costs of hospitalization for infectious diseases such as influenza, costs significantly lower than those described here.

Substantial Out-of-Pocket Health Expenditure on Prenatal Check-Ups: Estimates from a Sample of Pregnant Women in Cartagena, Colombia.

OBJECTIVE: We aimed to estimate out-of-pocket (OOP) health expenditures and the indirect costs related to prenatal check-ups in pregnant women seen in a maternity hospital in the Colombian Caribbean region. METHODS: We described the economic costs of pregnant women, with no age limits, who attended prenatal check-ups in a maternity hospital. To estimate OOP and indirect costs owing to prenatal check-ups in pregnant women, a survey was constructed, where the woman was asked about some sociodemographic variables, to characterize those attending the prenatal check-ups. Absolute and relative frequencies, averages and confidence intervals were used to characterize the population and estimate OOP and indirect costs in pregnant women. The latter were estimated from the percentile method. A bootstrapping was performed to reduce the bias within the analysis. RESULTS: In total, 56 pregnant women were surveyed, with an average age of 25.9 years (±6.2). All women surveyed had OOP associated to the prenatal check-up in at least one cost-item, and the OOP ranged between $0.3 and $108.7. Transportation was the item with the highest frequency of expenses, followed by food, other expenses, and drugs. The mean of OOP expenditures was $24.3 (CI 95% $18.1-31.4) for women who attended their prenatal check-up. DISCUSSION: Considering the estimated OOP health expenditures caused by prenatal check-ups by household income, women living with <1 minimum wage spend 7% of their income in a prenatal check-up. In women with 1-2 and >2-3 minimum wages, these proportions were 5%, 3%, respectively. Unfortunately, this makes prenatal care a significant source of economic burden, impacting poor households in Cartagena.

The burden of the most common rheumatic disease in Colombia.

BACKGROUND: Estimating the burden of rheumatic diseases (RDs) requires proper evaluation of its lethal and nonlethal consequences. In Colombia, it is possible to find local data and Global Burden of Disease (GBD) reports that collect information from varied contexts and apply complex statistical models, but no on-site estimations are available. METHODS: This was a descriptive study on the burden of RD based on occurrence and mortality data in the general population during 2015, including information and prevalence estimations from the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) study. Disability-adjusted life years (DALYs) were estimated by combining measures of years of life lost (YLL) and years lived with disability (YLDs). For disability weight estimations among cases, different COPCORD responses were mapped using flowcharts to show the severity distribution according to GBD. All model parameters and results were validated through an expert consensus panel. RESULTS: Low back pain (LBP) was the RD with the greatest burden of disease, costing 606.05 (95% CI 502.76-716.58) DALYs per 100,000 inhabitants, followed by osteoarthritis (292.11; 95% CI 205.76-386.85) and rheumatoid arthritis (192.46, 95% CI 109.7-239.69). CONCLUSIONS: The burden of RD is as high in Colombia as in other countries of the region. The results offer an interesting tool for optimizing healthcare system design as well as for planning the distribution of human and economic resources to achieve early diagnosis and adequate care of these diseases.

A multifunctional mannosyltransferase family in Candida albicans determines cell wall mannan structure and host-fungus interactions.

The cell wall proteins of fungi are modified by N- and O-linked mannosylation and phosphomannosylation, resulting in changes to the physical and immunological properties of the cell. Glycosylation of cell wall proteins involves the activities of families of endoplasmic reticulum and Golgi-located glycosyl transferases whose activities are difficult to infer through bioinformatics. The Candida albicans MNT1/KRE2 mannosyl transferase family is represented by five members. We showed previously that Mnt1 and Mnt2 are involved in O-linked mannosylation and are required for virulence. Here, the role of C. albicans MNT3, MNT4, and MNT5 was determined by generating single and multiple MnTDelta null mutants and by functional complementation experiments in Saccharomyces cerevisiae. CaMnt3, CaMnt4, and CaMnt5 did not participate in O-linked mannosylation, but CaMnt3 and CaMnt5 had redundant activities in phosphomannosylation and were responsible for attachment of approximately half of the phosphomannan attached to N-linked mannans. CaMnt4 and CaMnt5 participated in N-mannan branching. Deletion of CaMNT3, CaMNT4, and CaMNT5 affected the growth rate and virulence of C. albicans, affected the recognition of the yeast by human monocytes and cytokine stimulation, and led to increased cell wall chitin content and exposure of beta-glucan at the cell wall surface. Therefore, the MNT1/KRE2 gene family participates in three types of protein mannosylation in C. albicans, and these modifications play vital roles in fungal cell wall structure and cell surface recognition by the innate immune system.

The trend in mortality due to suicide in urban and rural areas of Colombia, 1979-2014 / Tendencia de la mortalidad por suicidio en las áreas urbanas y rurales de Colombia, 1979-2014

Introduction: Suicide is a serious social and public health problem that affects the population in most countries in the world. Differences in suicide rates in rural and urban areas have been previously described. Objective: To study the trend of mortality rates by suicide in Colombia, in rural and urban areas by gender, age group, and suicide method during the years 1979-2014. Materials and methods: We conducted a temporal trend ecologic study using death certificates from the Departamento Administrativo Nacional de Estadística, DANE. Specific and adjusted by age and gender mortality rates were calculated. We estimated negative binomial and inflection point regression models to study the trends in mortality rates stratified by gender, age group, and suicide method. Results: A total of 56,448 suicides was reported in Colombia between 1979 and 2014. The risk of suicide was higher in urban areas for men, individuals between 25 and 44 years, and 65 and over; and for those who used hanging as the suicide method. Also, the risk of suicide was higher in the rural area for men between 45 and 64 years old, and those who used firearms, sharp weapons, hanging, and others as suicide methods. The trend of suicide rates in urban areas showed its maximum peak in 1999 and in the rural ones in 2000. Then, in the two areas, there was a gradual decrease. Hanging in both areas presented a tendency to rise in men. Conclusions: Suicide has shown a tendency toward reduction after the year 2000, with differences between urban and rural areas.

Introducción. El suicidio es un grave problema social y de salud pública que afecta a la población de la mayoría de los países del mundo. Se han descrito diferencias en las tasas de suicidio entre las áreas rurales y las urbanas. Objetivo. Estudiar la tendencia de las tasas de mortalidad por suicidio en Colombia en las áreas de defunción rural y urbana y según sexo, grupo de edad y método de suicidio para el periodo 1979-2014. Materiales y métodos. Se realizó un estudio ecológico de tendencia temporal a partir de la información de mortalidad del Departamento Administrativo Nacional de Estadística. Se calcularon las tasas de mortalidad específica y ajustada por edad y sexo. Las tendencias de las tasas por área para el periodo de estudio, y tanto por sexo y grupo de edad como por método de suicidio, se estudiaron mediante modelos negativos de regresión binomial y regresión de puntos de inflexión. Resultados. Un total de 56.448 suicidios se registró en Colombia entre 1979 y 2014. El riesgo de suicidio fue más alto en el área urbana en hombres, en los grupos etarios de 25 a 44 años y de 65 y más años, y en quienes emplearon el ahorcamiento. El riesgo de suicidio fue mayor en el área rural para los hombres entre los 45 y los 64 años, y para aquellos que recurrieron al disparo de armas de fuego, armas cortantes, ahorcamiento y otros. La tendencia de las tasas en el área urbana mostró su máximo pico en 1999 y, en la rural, en el 2000; posteriormente, en ambas áreas se produjo un descenso paulatino. El ahorcamiento presentó una tendencia al ascenso en hombres en las dos áreas. Conclusión. El suicidio ha mostrado una tendencia hacia la reducción después del año 2000, con diferencias entre las áreas urbanas y las rurales.

Inequalities in health by regime of affiliation to the health system in events of obligatory notification, Colombia, 2015 / Desigualdades en salud según régimen de afiliación y eventos notificados al Sistema de Vigilancia (Sivigila) en Colombia, 2015

Introduction: Inequalities in the health field are caused by the differences in the social and economic conditions, that influence the disease risk and the measures taken to treat the disease. Objective: We aimed to estimate the social inequalities in health in Colombia, according to the type of affiliation to the health system as a proxy of socioeconomic status. Materials and methods: We conducted a retrospective descriptive analysis calculating incidence rates age and sex adjusted for all mandatory reporting events using the affiliation regime (subsidized and contributory) as a socioeconomic proxy. Estimates were made at departmental level for 2015. Social inequalities were calculated in terms of absolute and relative gaps. Results: We found social inequalities in the occurrence of mandatory reporting events in population affiliated to the Colombian subsidized regime (poor population). In this population, 82.31 cases of Plasmodium falciparum malaria per 100,000 affiliates were reported more than those reported in the contributory regime. Regarding the relative gap, belonging to the subsidized regime increased by 31.74 times the risk of dying from malnutrition in children under 5 years of age. Other events such as those related to sexual and reproductive health (maternal mortality, gestational syphilis and congenital syphilis); neglected diseases and communicable diseases related to poverty (leprosy and tuberculosis), also showed profound inequalities. Conclusion: In Colombia there are inequalities by regime of affiliation to the health system. Measured socioeconomic status was a predictor of increased morbidity and premature mortality.

Introducción. Las desigualdades en salud se generan por diferencias en las condiciones sociales y económicas, lo cual influye en el riesgo de enfermar y la forma de enfrentar la enfermedad. Objetivo. Evaluar las desigualdades sociales en salud en Colombia, utilizando el tipo de afiliación al sistema de salud como un parámetro representativo (proxy) de la condición socioeconómica. Materiales y métodos. Se trata de un análisis descriptivo y retrospectivo en el que se calcularon las tasas específicas de incidencia, ajustadas por edad y sexo, para eventos de notificación obligatoria, utilizando el régimen de afiliación (subsidiado o contributivo) como variable representativa del nivel socioeconómico. Las estimaciones se hicieron a nivel departamental para el 2015. Las desigualdades sociales se calcularon en términos de brechas absolutas y relativas. Resultados. Se evidencian desigualdades sociales en la ocurrencia de eventos de notificación obligatoria, las cuales desfavorecen a la población afiliada al régimen subsidiado. En esta población, se reportaron 82,31 casos más de malaria Plasmodium falciparum por 100.000 afiliados, que los notificados en el régimen contributivo. Respecto a la brecha relativa, el pertenecer al régimen subsidiado se asocia con un aumento de 31,74 veces del riesgo de morir por desnutrición en menores de cinco años. Otros eventos también presentaron profundas desigualdades, como los relacionados con la salud sexual y reproductiva (mortalidad materna, sífilis gestacional y sífilis congénita), las enfermedades infecciosas y las enfermedades transmisibles relacionadas con la pobreza (lepra y tuberculosis). Conclusión. El tipo de afiliación al Sistema General de Seguridad Social en Salud en Colombia es un buen indicador del nivel socioeconómico, y es un factor predictor de mayor morbilidad y mortalidad prematura asociada con los factores determinantes sociales de la salud.

Cost-effectiveness analysis of Mucosal Leishmaniasis diagnosis with PCR-based vs parasitological tests in Colombia.

To estimate the cost-effectiveness of available diagnosis alternatives for Mucosal Leishmaniasis (ML) in Colombian suspected patients. A simulation model of the disease's natural history was built with a decision tree and Markov models. The model´s parameters were identified by systematic review and validated by expert consensus. A bottom-up cost analysis to estimate the costs of diagnostic strategies and treatment per case was performed by reviewing 48 clinical records of patients diagnosed with ML. The diagnostic strategies compared were as follows: 1) no diagnosis; 2) parasite culture, biopsy, indirect immunofluorescence assay (IFA), and Montenegro skin test (MST) combined ; 3) parasite culture, biopsy, and IFA combined; 4) PCR-miniexon; and 5) PCR-kDNA. Three scenarios were modeled in patients with ML clinical suspicion, according to ML prevalence scenarios: high, medium and low. Adjusted sensitivity and specificity parameters of a combination of diagnostic tests were estimated with a discrete event simulation (DES) model. For each alternative, the costs and health outcomes were estimated. The time horizon was life expectancy, considering the average age at diagnosis of 31 years. Incremental cost-effectiveness ratios (ICERs) were calculated per Disability Life Year (DALY) avoided, and deterministic and probabilistic sensitivity analyses were performed. A threshold of willingness to pay (WTP) of three-time gross domestic product per capita (GDPpc) (US$ 15,795) and a discount rate of 3% was considered. The analysis perspective was the third payer (Health System). All costs were reported in American dollars as of 2015. PCR- kDNA was the cost-effective alternative in clinical suspicion levels: low, medium and high with ICERs of US$ 7,909.39, US$ 5,559.33 and US$ 4,458.92 per DALY avoided, respectively. ML diagnostic tests based on PCR are cost-effective strategies, regardless of the level of clinical suspicion. PCR-kDNA was the most cost-effective strategy in the competitive scenario with the parameters included in the present model.

Endoplasmic reticulum alpha-glycosidases of Candida albicans are required for N glycosylation, cell wall integrity, and normal host-fungus interaction.

The cell surface of Candida albicans is enriched in highly glycosylated mannoproteins that are involved in the interaction with the host tissues. N glycosylation is a posttranslational modification that is initiated in the endoplasmic reticulum (ER), where the Glc(3)Man(9)GlcNAc(2) N-glycan is processed by alpha-glucosidases I and II and alpha1,2-mannosidase to generate Man(8)GlcNAc(2). This N-oligosaccharide is then elaborated in the Golgi to form N-glycans with highly branched outer chains rich in mannose. In Saccharomyces cerevisiae, CWH41, ROT2, and MNS1 encode for alpha-glucosidase I, alpha-glucosidase II catalytic subunit, and alpha1,2-mannosidase, respectively. We disrupted the C. albicans CWH41, ROT2, and MNS1 homologs to determine the importance of N-oligosaccharide processing on the N-glycan outer-chain elongation and the host-fungus interaction. Yeast cells of Cacwh41Delta, Carot2Delta, and Camns1Delta null mutants tended to aggregate, displayed reduced growth rates, had a lower content of cell wall phosphomannan and other changes in cell wall composition, underglycosylated beta-N-acetylhexosaminidase, and had a constitutively activated PKC-Mkc1 cell wall integrity pathway. They were also attenuated in virulence in a murine model of systemic infection and stimulated an altered pro- and anti-inflammatory cytokine profile from human monocytes. Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions.

The DEAD-Box RNA Helicases of Bacillus subtilis as a Model to Evaluate Genetic Compensation Among Duplicate Genes.

The presence of duplicated genes in organisms is well documented. There is increasing interest in understanding how these genes subfunctionalize and whether functional overlap can explain the fact that some of these genes are dispensable. Bacillus subtilis possesses four DEAD-box RNA helicases (DBRH) genes, cshA, cshB, deaD/yxiN, and yfmL that make a good case to study to what extent they can complement each other despite their subfunctionalization. They possess the highly conserved N-terminal catalytic domain core common to RNA helicases, but different carboxy-terminal ends. All four genes have been shown to have independent functions although all participate in rRNA assembly. None of the B. subtilis DBRH is essential for growth at 37°C, and all single deletion mutants exhibit defective growth at 18°C except for ΔdeaD/yxiN. Evaluation of double mutants did not reveal negative epistasis, suggesting that they do not have overlapping functions. The absence of any one gene distorts the expression pattern of the others, but not in a specific pattern suggestive of compensation. Overexpression of these paralogous genes in the different mutant backgrounds did not result in cross-complementation, further confirming their lack of buffering capability. Since no complementation could be observed among full sized proteins, we evaluated to what extent the superfamily 2 (SF2) helicase core of the smallest DBRH, YfmL, could be functional when hooked to each of the C-terminal end of CshA, CshB, and DeaD/YxiN. None of the different chimeras complemented the different mutants, and instead, all chimeras inhibited the growth of the ΔyfmL mutant, and other combinations were also deleterious. Our findings suggest that the long time divergence between DEAD-box RNA helicase genes has resulted in specialized activities in RNA metabolism and shows that these duplicated genes cannot buffer one another.

Economic Costs of Chikungunya Virus in Colombia.

OBJECTIVE: The aim of the present study was to estimate the economic impact of chikungunya virus (CHIKV) infection in Colombia from a societal perspective. METHODS: We conducted a retrospective, bottom-up cost-of-illness study in clinically confirmed cases during the first chikungunya (CHIK) outbreak in Colombia in 2014. Direct and indirect costs were estimated per patient. Economic costs were calculated by the addition of direct costs (direct medical costs and out-of-pocket heath expenditures) and indirect cost as a result of loss of productivity. RESULTS: A total of 126 patients (67 children and 59 adults) with CHIK were included. The median of the direct medical cost in children was US$257.9 (interquartile range [IQR] 121.7-563.8), and US$66.6 (IQR 26.5-317.3) for adults. The productivity loss median expenditures reached US$81.3 (IQR 72.2-203.2) per adult patient. The median economic cost in adults as a result of CHIK was US$152.9 (IQR 101.0-539.6), of which 53.2% was a result of indirect costs. Out-of-pocket expenditures comprised 3.3% of all economic costs. CONCLUSIONS: Our study can help health decision makers to properly assess the burden of disease caused by CHIK in Colombia, an endemic tropical country. We recommend to strength the health information systems and to continue investing in public health measures to prevent CHIK.

Fungal Mannosyltransferases as Fitness Attributes and their Contribution to Virulence.

Fungal pathogens affect a wide variety of hosts, such as human beings, plants, animals, and insects. The course of infection relies on the virulence grade of the fungus and the strength of the defense mechanisms of the host. Virulence factors are closely related to the cell surface; cell wall proteins have a crucial role in adhesion, hyphal development, hydrophobicity, biofilm formation, immunomodulation and surface variation. The enzymes involved in cell wall biosynthesis are not proper virulence factors, but they are necessary for cell function. The deletion of the genes encoding those enzymes often results in an attenuation of virulence. Secreted proteins and cell wall proteins are modified with sugar residues through the N- and O- glycosylation pathways. A set of glycosidases and glycosyltransferases from the Endoplasmic Reticulum and Golgi bodies determine the outcome of the protein. Proper protein glycosylation is important for folding, localization and protein function. In fungi, the glycoproteins are particularly enriched with mannose moieties. In this review, the role of mannosyltransferases from the Pmt, Ktr/Mnt, Mnn and Och1families for the full development of fungal virulence is summarized and discussed.

[A model for mortality analysis in Colombia. 2000-2012]. / Modelo para el análisis de la mortalidad en Colombia 2000-2012.

OBJECTIVE: To propose and evaluate a model for fitting and forecasting the mortality rates in Colombia that allows analyzing the trends by age, sex, region and cause of death. METHODOLOGY: The national death registries were used as primary source of analysis. The data was pre-processed recodifying the cause of death and redistributing the garbage codes. The forecast model was formulated as a linear approximation with a set of variables of interest, in particular the population and gross domestic product (GDP) by region. RESULTS: As study case we took the mortality under 5 years old, it decreased steadily since 2000 at the national level and at most of the regions. The predictive power of the proposed methodology was tested by fitting the model with the data from 2000 to 2011, the forecast for 2012 was compared with the actual rate, and these results show the model is reliable enough for most of the region-cause combinations. CONCLUSIONS: The proposed methodology and model have the potential to become an instrument to guide health spending priorities using some kind of evidence.

OBJETIVO: Proponer y evaluar un modelo para el ajuste y predicción de la mortalidad en Colombia que permita analizar tendencias por edad, sexo, Departamento y causa. METODOLOGÍA: Los registros de defunciones no fetales fueron utilizados como fuente primaria de análisis. Estos datos se pre-procesaron recodificando las causas y redistribuyendo los códigos basura. El modelo de predicción se formuló como una aproximación lineal de un conjunto de variables de interés, en particular la población y el producto interno bruto departamental. RESULTADOS: Como caso particular de estudio se tomó la mortalidad de menores de 5 años, se observó una disminución sostenida a partir del año 2000 tanto a nivel nacional como departamental, con excepción de tres departamentos. La evaluación del poder predictivo de la metodología propuesta se realizó ajustando el modelo con los datos de 2000 a 2011, la predicción para el 2012 fue comparada con la tasa observada, estos resultados muestran que el modelo es suficientemente confiable para la mayor parte de las combinaciones departamento-causa. CONCLUSIONES: La metodología y modelo propuesto tienen el potencial de convertirse en un instrumento que permita orientar las prioridades del gasto en salud utilizando algún tipo de evidencia.

Saccharomyces cerevisiae KTR4, KTR5 and KTR7 encode mannosyltransferases differentially involved in the N- and O-linked glycosylation pathways.

Saccharomyces cerevisiae is a model to understand basic aspects of protein glycosylation pathways. Although these metabolic routes have been thoroughly studied, there are still knowledge gaps; among them, the role of the MNT1/KRE2 gene family. This family is composed of nine members, with only six functionally characterized. The enzymes Ktr1, Ktr3, and Mnt1/Kre2 have overlapping activities in both O-linked and N-linked glycan synthesis; while Ktr2 and Yur1 participate exclusively in the elongation of the N-linked glycan outer chain. KTR6 encodes for a phosphomannosyltransferase that synthesizes the cell wall phosphomannan. Here, we aimed to establish the functional role of KTR4, KTR5 and KTR7 in the protein glycosylation pathways, by using heterologous complementation in Candida albicans null mutants lacking members of the MNT1/KRE2 gene family. The three S. cerevisiae genes restored defects in the C. albicans N-linked glycosylation pathway. KTR5 and KTR7 partially complemented a C. albicans null mutant with defects in the synthesis of O-linked glycans, and only KTR4 fully elongated the O-linked glycans like wild-type cells. Therefore, our results suggest that the three genes have a redundant activity in the S. cerevisiae N-linked glycosylation pathway, but KTR4 plays a major role in O-linked glycan synthesis.

Phosphomannosylation and the Functional Analysis of the Extended Candida albicans MNN4-Like Gene Family.

Phosphomannosylation is a modification of cell wall proteins that occurs in some species of yeast-like organisms, including the human pathogen Candida albicans. These modified mannans confer a negative charge to the wall, which is important for the interactions with phagocytic cells of the immune systems and cationic antimicrobial peptides. In Saccharomyces cerevisiae, the synthesis of phosphomannan relies on two enzymes, the phosphomannosyltransferase Ktr6 and its positive regulator Mnn4. However, in C. albicans, at least three phosphomannosyltransferases, Mnn4, Mnt3 and Mnt5, participate in the addition of phosphomannan. In addition to MNN4, C. albicans has a MNN4-like gene family composed of seven other homologous members that have no known function. Here, using the classical mini-Ura-blaster approach and the new gene knockout CRISPR-Cas9 system for gene disruption, we generated mutants lacking single and multiple genes of the MNN4 family; and demonstrate that, although Mnn4 has a major impact on the phosphomannan content, MNN42 was also required for full protein phosphomannosylation. The reintroduction of MNN41, MNN42, MNN46, or MNN47 in a genetic background lacking MNN4 partially restored the phenotype associated with the mnn4Δ null mutant, suggesting that there is partial redundancy of function between some family members and that the dominant effect of MNN4 over other genes could be due to its relative abundance within the cell. We observed that additional copies of alleles number of any of the other family members, with the exception of MNN46, restored the phosphomannan content in cells lacking both MNT3 and MNT5. We, therefore, suggest that phosphomannosylation is achieved by three groups of proteins: [i] enzymes solely activated by Mnn4, [ii] enzymes activated by the dual action of Mnn4 and any of the products of other MNN4-like genes, with exception of MNN46, and [iii] activation of Mnt3 and Mnt5 by Mnn4 and Mnn46. Therefore, although the MNN4-like genes have the potential to functionally redundant with Mnn4, they apparently do not play a major role in cell wall mannosylation under most in vitro growth conditions. In addition, our phenotypic analyses indicate that several members of this gene family influence the ability of macrophages to phagocytose C. albicans cells.

Trends in diabetes mortality identified from death certificates in Colombia, 1979-2017 / Tendencias de la mortalidad por diabetes identificadas a partir de los certificados de defunción en Colombia, 1979-2017

ABSTRACT Objective. To describe the mortality trends of diabetes mellitus (DM) in Colombia, by sex and age group, from 1979 to 2017. Methods. We carried out an ecological study using mortality data from the Colombian National Administrative Department of Statistics. Crude and age-standardized annual mortality rates per 100 000 people were estimated. Trends of standardized rates were described by sex and age groups. Joinpoint regression models were performed to study mortality trends. Results. Throughout the whole period, the total number of DM recorded deaths in Colombia was 200 650, 58% (116 316) in women (p<0.05). The age-standardized mortality rates (ASMR) by sex increased from 13.2 to 26.6 deaths per 100 000 in women and from 10.1 to 22.7 in men from 1979 to 1999. We observed a decrease from 26.6 to 15.4 per 100 000 in women, and from 22.7 to 15.9 in men for the period 1999-2017. The joinpoint regression analysis showed that the average annual percentage change of the period did not vary in both sexes (men: -0.2%, 95% CI -1.0 to 1.4%; women: 0.7%, 95% CI -0.1 to 1.6%). Conclusions. The DM mortality showed a decreasing trend after 2000 in women and 2004 in men. Primary and secondary prevention programs must continue to be strengthened for an earlier diagnosis of diabetes.

RESUMEN Objetivo. Describir las tendencias de la mortalidad por diabetes mellitus (DM) en Colombia, por sexo y grupo de edad, entre 1979 y 2017. Métodos. Estudio ecológico con datos de mortalidad del Departamento Administrativo Nacional de Estadística de Colombia. Se estimaron las tasas de mortalidad anuales brutas y ajustadas por edad por cada 100 000 personas. Se describieron las tendencias de las tasas ajustadas por sexo y grupos de edad. Se realizaron modelos de regresión joinpoint para estudiar las tendencias de la mortalidad. Resultados. En el período del estudio, el número total de muertes por DM registradas en Colombia fue de 200 650, el 58% (116 316) en mujeres (p<0,05). Las tasas de mortalidad ajustadas por edad, en cada sexo, aumentaron de 13,2 a 26,6 muertes por 100 000 en las mujeres y de 10,1 a 22,7 en los hombres entre 1979 y 1999. En el período 1999-2017 se observó una disminución de 26,6 a 15,4 por 100 000 en las mujeres y de 22,7 a 15,9 en los hombres. El análisis de regresión joinpoint demostró que el cambio porcentual anual medio del período no varió en ambos sexos (hombres: -0,2%, IC 95% -1,0 a 1,4%; mujeres: 0,7%, IC 95% -0,1 a 1,6%). Conclusiones. La mortalidad por DM mostró una tendencia decreciente después del año 2000 en las mujeres y del 2004 en los hombres. Es necesario seguir fortaleciendo los programas de prevención primaria y secundaria a fin de alcanzar un diagnóstico más temprano de la diabetes.

Trends in diabetes mortality identified from death certificates in Colombia, 1979-2017

[ABSTRACT]. Objective. To describe the mortality trends of diabetes mellitus (DM) in Colombia, by sex and age group, from 1979 to 2017. Methods. We carried out an ecological study using mortality data from the Colombian National Administrative Department of Statistics. Crude and age-standardized annual mortality rates per 100 000 people were estimated. Trends of standardized rates were described by sex and age groups. Joinpoint regression models were performed to study mortality trends. Results. Throughout the whole period, the total number of DM recorded deaths in Colombia was 200 650, 58% (116 316) in women (p<0.05). The age-standardized mortality rates (ASMR) by sex increased from 13.2 to 26.6 deaths per 100 000 in women and from 10.1 to 22.7 in men from 1979 to 1999. We observed a decrease from 26.6 to 15.4 per 100 000 in women, and from 22.7 to 15.9 in men for the period 1999-2017. The joinpoint regression analysis showed that the average annual percentage change of the period did not vary in both sexes (men: -0.2%, 95% CI –1.0 to 1.4%; women: 0.7%, 95% CI –0.1 to 1.6%). Conclusions. The DM mortality showed a decreasing trend after 2000 in women and 2004 in men. Primary and secondary prevention programs must continue to be strengthened for an earlier diagnosis of diabetes.

[RESUMEN]. Objetivo. Describir las tendencias de la mortalidad por diabetes mellitus (DM) en Colombia, por sexo y grupo de edad, entre 1979 y 2017. Métodos. Estudio ecológico con datos de mortalidad del Departamento Administrativo Nacional de Estadística de Colombia. Se estimaron las tasas de mortalidad anuales brutas y ajustadas por edad por cada 100 000 personas. Se describieron las tendencias de las tasas ajustadas por sexo y grupos de edad. Se realizaron modelos de regresión joinpoint para estudiar las tendencias de la mortalidad. Resultados. En el período del estudio, el número total de muertes por DM registradas en Colombia fue de 200 650, el 58% (116 316) en mujeres (p<0,05). Las tasas de mortalidad ajustadas por edad, en cada sexo, aumentaron de 13,2 a 26,6 muertes por 100 000 en las mujeres y de 10,1 a 22,7 en los hombres entre 1979 y 1999. En el período 1999-2017 se observó una disminución de 26,6 a 15,4 por 100 000 en las mujeres y de 22,7 a 15,9 en los hombres. El análisis de regresión joinpoint demostró que el cambio porcentual anual medio del período no varió en ambos sexos (hombres: –0,2%, IC 95% –1,0 a 1,4%; mujeres: 0,7%, IC 95% –0,1 a 1,6%). Conclusiones. La mortalidad por DM mostró una tendencia decreciente después del año 2000 en las mujeres y del 2004 en los hombres. Es necesario seguir fortaleciendo los programas de prevención primaria y secundaria a fin de alcanzar un diagnóstico más temprano de la diabetes.