The Costa Rican Social Security Fund (Spanish: Caja Costarricense de Seguro Social) is in charge of most of the nation's public health sector. Its role in public health (as the administrator of health institutions) is key in Costa Rica, playing an important part in the state's national health policy making.Its services are available to all citizens and permanent legal residents. This governmental entity's functions encompass both the administrative and functional aspects. Originally, services were carried out at private hospitals but funded by the Costa Rican Social Security Fund. Not until the mid-1960s did the Caja begin constructing its own hospitals staffed by public employees. It has the obligation (as a public institution) to formulate and execute health programs that are both preventive (such as: vaccination, informational, fumigation, etc.) and healing (such as: surgery, radiation therapy, pharmacy, clinical, etc.) in nature.The Costa Rican Social Security Fund is also charged with the administration of the public pension system.
Germline defects in mismatch repair (MMR) genes are known to significantly increase the risk of developing certain types of cancers, notably colorectal and endometrial cancers. These conditions are characterized under Lynch syndrome. Accurate diagnosis of this predisposition, along with meaningful predictive testing for family members, necessitates the identification of pathogenic variants. However, classifying small coding genetic variants identified in cancer patients is very challenging, specifically in the case of PMS2 variants, since PMS2 pathogenic variants display a lower penetrance and less severe phenotype and therefore a lower tumor burden in affected families. We have assembled clinical data on four PMS2 missense variants of uncertain significance (VUS) identified in 23 patients (p.(Asp286Gly), p.(Asn335Ser), p.(Ile679Thr) and p.(Arg799Trp)). For these variants, functional testing was performed (RNA splicing, protein stability and catalytic activity). Since many protein ortholog sequences and accurate predictive models from AlphaFold2 are available, we also included a systematic analysis of residue conservation and structural role (ConStruct assessment). Overall, our findings indicate that p.(Asp286Gly) and p.(Arg799Trp) behave similarly to wild-type PMS2 and are thus probably neutral. In contrast, p.(Asn335Ser) and p.(Ile679Thr) conferred defects in protein expression or MMR activity. These could be explained by the relevant roles of these amino acids in MLH1-PMS2-N-terminal dimerization (p.Asn335) and C-terminal dimerization (p.Ile679). Our data thus suggest that p.(Asp286Gly) and p.(Arg799Trp) are benign, while the tumor risk in the other two variants remains to be established. Taken together, we suggest roadmaps for the individualized evaluation of difficult uncertain variants by comprising information from all available sources.
Histoplasmosis remains an important endemic mycosis in tropical countries, yet comprehensive epidemiological data from Central America are limited. We aimed to describe the epidemiologic characteristics of histoplasmosis in Costa Rica during a 16-year period.Annual Distribution and Demographic CharacteristicsAnnual Distribution and Demographic Characteristics of Histoplasmosis in Costa Rica, 2000-2015Clinical Characteristics and Mortality RatesClinical Characteristics and Mortality Rates of Histoplasmosis in Costa Rica, 2000-2015 We conducted a retrospective, descriptive study analyzing all histoplasmosis cases (n=434) registered in the national hospital discharge database of Costa Rica's Social Security System from 2000-2015. We calculated cumulative incidence per 100,000 population, analyzed demographic distribution, comorbidities, clinical presentations, and in-hospital mortality.Relationship Between HIV Status and Type of HistoplasmosisRelationship Between HIV Status and Type of Histoplasmosis in Costa Rica, 2000-2015Geographic Distribution and Seasonal Patterns of HistoplasmosisGeographic Distribution and Seasonal Patterns of Histoplasmosis in Costa Rica, 2000-2015 The cumulative incidence was 0.62 cases/100,000 person-years, with temporal variations showing an initial increase followed by a slight decline. Males were predominantly affected (73.3%; RR=2.68, 95%CI:2.17-3.31). Median age was 31 years (IQR:18-43), with 26% of cases in patients < 19 years and 59% between 20-49 years. HIV infection was present in 49.3% of patients, while 46% had other comorbidities including cancer (5.3%), chronic liver disease (2.5%), and kidney transplant (2.5%); 5.1% had no underlying conditions. Clinical presentations were classified as pulmonary (25.8%), disseminated (27.6%), and undetermined (46.5%). Overall in-hospital mortality was 14.5%, being significantly higher in disseminated disease (25%) and elderly patients (31.3% in 60-69 age group). Surprisingly, patients without documented comorbidities had the highest mortality rate (27.3%). Geographic distribution showed predominance in San José (36.9%), Alajuela (18.2%), and Limón (13.8%) provinces. Incidence peaks occurred during 2005-2006 (44 cases/year), with July showing the highest diagnostic frequency (12.9%). Histoplasmosis in Costa Rica maintains a relatively stable incidence, primarily affecting young adults with a strong association with HIV infection. The unexpectedly high mortality in patients without apparent risk factors suggests potential delayed diagnosis or unidentified factors requiring further investigation. The disseminated form carries the highest mortality risk, emphasizing the need for early detection strategies, particularly in high-risk populations. All Authors: No reported disclosures
Candida species represent 80% of nosocomial fungal infections, with candidemia being the most frequent invasive disease. In Latin America, Candida resistance is generally low, but information from Central America is scarce. We aimed to describe antifungal susceptibility of Candida species isolated from bloodstream infections at two national adult hospitals in Costa Rica from 2012 to 2023. This retrospective study analyzed the first isolate from candidemia episodes caused by C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata with available susceptibility results. Testing used VITEK 2 system. Interpretation followed CLSI M27M44S-Ed3 guidelines. Amphotericin B susceptibility was defined as MIC ≤1μg/ml. Differences between species were assessed using Fisher's exact test, and temporal trends with chi-square test. We analyzed 1,390 isolates: C. parapsilosis 689 (49.6%), C. albicans 448 (32.2%), C. tropicalis 131 (9.4%), and C. glabrata 122 (8.8%). Fluconazole susceptibility was high in C. albicans (97.1%) and C. tropicalis (96.2%), but lower in C. parapsilosis (40.6%, p< 0.001). C. glabrata isolates were predominantly susceptible-dose dependent (96.1%). Voriconazole showed high activity against C. albicans (98.7%) and C. tropicalis (96.9%), but resistance in C. parapsilosis (20.2%). Amphotericin B maintained excellent activity against all species (98.7% overall). Echinocandins demonstrated high efficacy against C. albicans, C. tropicalis, and C. parapsilosis (≥99%), but reduced activity against C. glabrata (caspofungin 41.3% susceptible, micafungin with 70.6% intermediate and 29.4% resistant). No significant temporal trends in susceptibility were observed over the 12-year period. Our findings reveal significant azole resistance in C. parapsilosis, particularly to fluconazole (59.4%) and voriconazole (20.2%). Amphotericin B maintains excellent activity against all species. Echinocandins remain highly effective against most Candida species except C. glabrata. These patterns have important implications for empirical antifungal therapy selection in our region. All Authors: No reported disclosures
