Frailty as a predictor of mortality: a comparative cohort study of older adults in Costa Rica and the United States.

BACKGROUND: Frailty is a common condition among older adults that results from aging-related declines in multiple systems. Frailty increases older adults' vulnerability to negative health outcomes, including loss of mobility, falls, hospitalizations, and mortality. The aim of this study is to examine the association between frailty and mortality in older adults from Costa Rica and the United States. METHODS: This prospective cohort study uses secondary nationally-representative data of community-dwelling older adults from the Costa Rican Longevity and Healthy Aging Study (CRELES, n = 1,790) and the National Health & Aging Trends Study (NHATS, n = 6,680). Frailty status was assessed using Physical Frailty Phenotype, which includes the following five criteria: shrinking, exhaustion, low physical activity, muscle weakness, and slow gait. We used Cox proportional hazard models to examine the association between frailty and all-cause mortality, including sociodemographic characteristics and health behaviors as covariates in the models. Mortality follow-up time was right censored at 8 years from the date at baseline interview. RESULTS: The death hazard for frail compared to non-frail older adults was three-fold in Costa Rica (HR = 3.14, 95% CI: 2.13-4.62) and four-fold in the White US (HR = 4.02, 95% CI: 3.04-5.32). Older age, being male, and smoking increased mortality risk in both countries. High education was a protective factor in the US, whereas being married/in union was a protective factor in Costa Rica. In the US, White older adults had a lower risk of death compared to all other races and ethnicities. CONCLUSIONS: Results indicate that frailty can have a differential impact on mortality depending on the country. Access to universal health care across the life course in Costa Rica and higher levels of stress and social isolation in the US may explain differences observed in end-of-life trajectories among frail older adults.

Seroprevalence and detection of bovine leukosis virus in semen from breeding bulls in Costa Rica.

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a persistent infection and the most important neoplastic disease in cattle. It is spread primarily by transferring infected lymphocytes through blood from carriers to healthy animals. The present study is aimed at determining the seropositivity of BLV in breeding bulls from Costa Rica and at detecting for the first time in the country BLV DNA in bull semen. Between May 2011 and August 2018, 379 blood and 133 semen samples were collected from bulls distributed in 118 farms. The serum was analyzed by an enzymatic immunoassay and the semen by polymerase chain reaction and sequencing. BLV seropositivity was 43.5% (165/379), while 64.4% (76/118) of the farms had positive reactors. Holstein (75.7%) and Jersey (73.0%) breeds showed the highest seropositivity. In addition, Bos taurus bulls (68.1%), older than seven years (50.0%), and those belonging to dairy farms (75.5%) had higher seropositivity compared to Bos indicus (17.7%), younger than seven years (42.2%), and those from beef farms (15.5%), respectively. Moreover, Bos taurus bulls had a higher risk of being seropositive than Bos indicus (OR = 3.4; 95% CI: 1.7-6.8). BLV DNA was found in one semen sample (2.5%; 1/40) from a seropositive bull. The importance of serum and molecular BLV screening in semen samples and the potential role of some risk factors associated with the disease, such as the bull's age, genotype, and type of livestock productive system, is argued in the present report.

The First Population-Level Description of Women Diagnosed With Invasive Breast Cancer in Costa Rica From 2008 to 2012: A Cross-Sectional Study.

INTRODUCTION: Breast cancer is the leading cause of cancer-related deaths among women worldwide. In Costa Rica, it ranks first in incidence and fourth in terms of mortality. However, there is a lack of comprehensive information on treatment patterns and outcomes for breast cancer patients in Costa Rica. METHODS: This study utilized data from the National Tumor Registry, which was merged with the Costa Rica Social Security Fund (CCSS) to ensure comprehensive access to clinical information. The study is prospective and focused on patients diagnosed with breast cancer between January 2008 and December 2012. This combined dataset allowed for a more comprehensive analysis of patient characteristics, treatment patterns, and outcomes related to breast cancer in Costa Rica. RESULTS: Among the 4775 patients diagnosed during this period, 3160 met the inclusion criteria for our study. The average age at diagnosis was 59.1 years, with 32.5% of patients being over the age of 65. Most of the patients (55.4%) identified themselves as homemakers, while 46.5% underwent core needle biopsy for diagnosis. Approximately 60% of women were diagnosed with early-stage disease (IA, IIA, and IIB), while 1.7% had metastatic disease, mainly affecting the bone. The mean interval between diagnosis and surgery was 72 days. Most patients (88.7%) received surgery as their initial treatment, and over half (54.4%) received some form of adjuvant therapy. Additionally, 85.6% of patients completed their prescribed treatment. CONCLUSION: This study provides a comprehensive and detailed description of the characteristics and treatment patterns among breast cancer patients in Costa Rica. The findings contribute to our understanding of the disease in this population and can serve as a foundation for further research and improvement in breast cancer management and care.

Estimating human papillomavirus vaccine efficacy from a single-arm trial: proof-of-principle in the Costa Rica Vaccine Trial.

BACKGROUND: The World Health Organization recommends a 1- or 2-dose human papillomavirus (HPV) vaccination schedule for females aged 9 to 20 years. Studies confirming the efficacy of a single dose and vaccine modifications are needed, but randomized controlled trials are costly and face logistical and ethical challenges. We propose a resource-efficient single-arm trial design that uses untargeted and unaffected HPV types as controls. METHODS: We estimated HPV vaccine efficacy (VE) from a single arm by comparing 2 ratios: the ratio of the rate of persistent incident infection with vaccine-targeted HPV 16 and 18 (HPV 16/18) and cross-protected types HPV 31, 33, and 45 (HPV 31/33/45) to vaccine-unaffected types HPV 35, 39, 51, 52, 56, 58, 59, and 66 (HPV 35/39/51/52/56/58/59/66) vs the ratio of prevalence of these types at the time of trial enrollment. We compare VE estimates using only data from the bivalent HPV 16/18 vaccine arm of the Costa Rica Vaccine Trial with published VE estimates that used both the vaccine and control arms. RESULTS: Our single-arm approach among 3727 women yielded VE estimates against persistent HPV 16/18 infections similar to published 2-arm estimates from the trial (according-to-protocol cohort: 91.0% , 95% CI = 82.9% to 95.3% [single-arm] vs 90.9% , 95% CI = 82.0% to 95.9% [2-arm]; intention-to-treat cohort: 41.7%, 95% CI = 32.4% to 49.8% [single-arm] vs 49.0% , 95% CI = 38.1% to 58.1% [2-arm]). VE estimates were also similar in analytic subgroups (number of doses received; baseline HPV serology status). CONCLUSIONS: We demonstrate that a single-arm design yields valid VE estimates with similar precision to a randomized controlled trial. Single-arm studies can reduce the sample size and costs of future HPV vaccine trials while avoiding concerns related to unvaccinated control groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00128661.

Health inequalities in cause-specific mortality in Costa Rica: a population-based cohort study.

OBJECTIVE: To analyze health inequalities in cause-specific mortality in Costa Rica from 2010 to 2018, observing the main causes for inequality in the country. METHODS: The National Electoral Rolls were used to follow-up all Costa Rican adults aged 20 years or older from 2010 to 2018 (n = 2,739,733) in an ecological study. A parametric survival model based on the Gompertz distribution was performed and the event death was classified according to the ICD-10. RESULTS: After adjustment for urbanicity, the poorest districts had a higher mortality than the wealthier districts for most causes of death except neoplasms, mental and behavioral disorders, and diseases of the nervous system. Urban districts showed significantly higher mortality than mixed and rural districts after adjustment for wealth for most causes except mental and behavioral disorders, diseases of the nervous system, and diseases of the respiratory system. Differences according to wealth were more frequent in women than men, whereas differences according to urbanicity were more frequent in men than in women. CONCLUSIONS: The study's findings were consistent, but not fully similar, to the international literature.

Integrated surveillance strategy to support the prevention of neural tube defects through food fortification with folic acid: the experience of Costa Rica.

PURPOSE: (1) To describe how Costa Rica implemented an integrated surveillance strategy of folate deficiency, neural tube defects (NTDs) prevalence, NTDs-associated infant mortality rate (NTDs-IMR), and folic acid food fortification (FAFF), to support with evidence NTDs prevention policies; (2) to disseminate updated data from monitoring programs. METHODS: We performed a cross-sectional analysis, using the databases of national surveillance systems for NTDs outcomes to compare NTDs-prevalence and NTDs-IMR observed in the pre-fortification (1987-1998) and post-fortification (2010-2020) periods. In addition, using data from FAFF monitoring program (2010-2020), means of folic acid concentration (mg/kg) and folic acid daily intake (µg/day) were calculated for each fortified food (corn and wheat flour, rice and milk), as well as its contribution to folic acid estimated average requirement (EAR). RESULTS: After FAFF Costa Rica showed a decrease of 84% in folic acid deficiency in women of childbearing age, as well as a 53% decrease in the prevalence of NTDs, falling from 11.82/10,000 to 5.52/10,000 livebirths. In addition, there was a 76% reduction in the NTDs-IMR from 77.01/100,000 to 18.66/100,000 livebirths. Between 2010 and 2020, all fortified foods provided an average contribution of 119% of the EAR of folic acid in the population. CONCLUSION: To reduce NTD risk, an integrated surveillance strategy is essential not only to base prevention strategies on evidence, but also to demonstrate their impact and improve interventions over time. The experience in Costa Rica provides evidence that this type of surveillance is feasible to be implemented in developing countries.

Molecular typing of bovine papillomaviruses in Costa Rica.

Bovine papillomaviruses are related to cause fibroepithelial proliferations in the skin and mucosae and are associated with economic loss mainly related to poor body condition and reduced milk production. This study aimed to investigate the presence and types of bovine papillomaviruses (BPVs) in cattle sampled in different areas of Costa Rica using molecular techniques. A descriptive study with a non-probability convenience sampling was carried out. A total of 99 papillomatous lesions were collected from 63 animals in 32 farms, and analyzed by polymerase chain reaction, rolling circle amplification (RCA), sequencing, and restriction enzymes digestion. Seven bovine papillomavirus types (BPV1, BPV2, BPV4, BPV6, BPV7, BPV10, BPV11) and two putative novel viral variants (BPV-CR1 and BPV-CR2) were identified for the first time in Costa Rica. BPV6 was the most frequently detected virus in lesions (31.2%), followed by BPV2 (25%) and BPV1 (25%). BPV1 and BPV2 were the most widely distributed in the Country. Coinfections were recorded in two animals (BPV1 / BPV2 and BPV4 / BPV6). Restriction analyses allowed differentiating BPV1 from BPV2, BPV4, and BPV7, but failed to identify BPV6, BPV10, and BPV11. Results suggest that a great PVs diversity is harbored by bovines in Costa Rica and indicate the need for further investigations aimed to uncover PV diversity at the full genomic level.

Diet-Attributable Greenhouse Gas Emissions and Acute Myocardial Infarction in Costa Rica Heart Study.

Adopting sustainable dietary patterns is essential for planetary and human health. As data to address this issue are lacking in Latino populations, this study examined the association between diet-attributable greenhouse gas emissions (GHGEs) and myocardial infarction (MI) in a Costa Rica Heart Study. This analysis included 1817 cases of a first non-fatal acute MI during hospitalization and their matched population-based controls, by age, sex, and area of residence. A validated food frequency questionnaire was used to quantify habitual dietary intake and diet-attributable GHGEs (kg CO2 equivalent (eq.)/year). Due to the matching design, conditional logistic regression was used. Red meat consumption contributed approximately 50% to the total diet-attributable GHGEs among both cases and controls. Higher diet-attributable GHGEs were associated with increased odds of acute MI. The odds of MI were 63% higher (OR = 1.63; 95% CI 1.20-2.21) among participants in the highest quintile (median diet-attributable GHGEs = 6247 kg CO2 eq./year) compared to the lowest quintile (median diet-attributable GHGEs = 2065 kg CO2 eq./year). An increasing linear trend in the odds of acute MI and diet-attributable GHGEs was detected (p-trend 0.0012). These findings highlight the importance of reducing red meat consumption to sustainably mitigate the incidence of MI and improve planetary health.

Emerging Lagochilascaris minor infections in domestic cats from Costa Rica: A zoonotic threat for the region.

Two cases of lagochilascariasis minor in domestic cats from Costa Rica within a period of two months are recorded for the first time in Central America. Clinical findings included purulent discharge and a tumor in the left ear in one of the cats, whereas the other cat had an ulcerated cervical lesion. Both patients underwent surgical procedures during which nematode worms were collected and analyzed. The collected nematodes were identified using a combination of morphological and molecular assays, which revealed a 99.1% similarity in the cytochrome oxidase subunit 1 with L. minor from Mexico. The lack of information on this parasitosis, as well as the enormous harm it does to animal and human hosts, highlights the need for more research and awareness in Costa Rica and Central America. Furthermore, the unexpected occurrence of these instances in the same location emphasizes the imminent zoonotic risk to humans and the active circulation of the parasite.

Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial.

BACKGROUND: In women vaccinated against human papillomavirus (HPV), reductions in cervical disease and related procedures results in more women having intact transformation zones, potentially increasing the risk of cervical lesions caused by non-vaccine-preventable HPV types, a phenomenon termed clinical unmasking. We aimed to evaluate HPV vaccine efficacy against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) attributed to non-preventable HPV types in the long-term follow-up phase of the Costa Rica HPV Vaccine Trial (CVT). METHODS: CVT was a randomised, double-blind, community-based trial done in Costa Rica. Eligible participants were women aged 18-25 years who were in general good health. Participants were randomly assigned (1:1) to receive an HPV 16 and 18 AS04-adjuvanted vaccine or control hepatitis A vaccine, using a blocked randomisation method (permuted block sizes of 14, 16, and 18). Vaccines in both groups were administered intramuscularly with 0·5 mL doses at 0, 1, and 6 months. Masking of vaccine allocation was maintained throughout the 4-year randomised trial phase, after which participants in the hepatitis A virus vaccine control group were provided the HPV vaccine and exited the study; a screening-only, unvaccinated control group was enrolled. The unvaccinated control group and HPV vaccine group were followed up for 7 years, during which treatment allocation was not masked. One of the prespecified primary endpoints for the long-term follow-up phase was precancers associated with HPV types not prevented by the vaccine, defined as histologically confirmed incident CIN2+ events or CIN3+ events attributed to any HPV type except HPV 16, 18, 31, 33, and 45. Our primary analytical period was years 7-11. Primary analyses were in all participants with at least one follow-up visit and excluded participants with a previous endpoint (ie, modified intention-to-treat cohort). Safety endpoints have been reported elsewhere. This trial is registered with ClinicalTrials.gov, NCT00128661 and NCT00867464. The randomised, masked trial phase is completed; an unmasked subset of women in the HPV-vaccinated group is under active investigation. FINDINGS: Between June 28, 2004, and Dec 21, 2005, 7466 participants were enrolled (HPV vaccine group n=3727 and hepatitis A virus vaccine control group n=3739). Between March 30, 2009, and July 5, 2012, 2836 women enrolled in the new unvaccinated control group. The primary analytical cohort (years 7 to 11) included 2767 participants in the HPV vaccine group and 2563 in the unvaccinated group for the CIN2+ events endpoint assessment and 2826 participants in the HPV vaccine group and 2592 in the unvaccinated control group for the CIN3+ events endpoint assessment. Median follow-up during years 7 to 11 for women included for the CIN2+ events analysis was 52·8 months (IQR 44·0 to 60·7) for the HPV vaccine group and 49·8 months (42·0 to 56·9) for the unvaccinated control group. During years 7 to 11, clinical unmasking was observed with a negative vaccine efficacy against CIN2+ events attributed to non-preventable HPV types (-71·2% [95% CI -164·0 to -12·5]), with 9·2 (95% CI 2·1 to 15·6) additional CIN2+ events attributed to non-preventable HPV types per 1000 HPV-vaccinated participants versus HPV-unvaccinated participants. 27·0 (95% CI 14·2 to 39·9) fewer CIN2+ events irrespective of HPV type per 1000 vaccinated participants were observed during 11 years of follow-up. Vaccine efficacy against CIN3+ events attributed to non-preventable HPV types during years 7 to 11 was -135·0% (95% CI -329·8 to -33·5), with 8·3 (3·0 to 12·8) additional CIN3+ events attributed to non-preventable HPV types per 1000 vaccinated participants versus unvaccinated participants. INTERPRETATION: Higher rates of CIN2+ events and CIN3+ events due to non-preventable HPV types in vaccinated versus unvaccinated participants suggests clinical unmasking could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programmes in screened populations. Importantly, the net benefit of vaccination remains considerable; therefore, HPV vaccination should still be prioritised as primary prevention for cervical cancer. FUNDING: National Cancer Institute and National Institutes of Health Office of Research on Women's Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Kidney Function in Rice Workers Exposed to Heat and Dehydration in Costa Rica.

The aim of this study was to evaluate heat exposure, dehydration, and kidney function in rice workers over the course of three months, in Guanacaste, Costa Rica. We collected biological and questionnaire data across a three-month-period in male field (n = 27) and other (n = 45) workers from a rice company where chronic kidney disease of unknown origin (CKDu) is endemic. We used stepwise forward regression to determine variables associated with estimated glomerular filtration rate eGFR at enrollment and/or change in eGFR, and Poisson regression to assess associations with incident kidney injury (IKI) over the course of three months. Participants were 20−62 years old (median = 40 in both groups). Dehydration was common (≥37%) in both groups, particularly among other workers at enrollment, but field workers were more exposed to heat and had higher workloads. Low eGFR (<60 mL/min/1.73 m2) was more prevalent in field workers at enrollment (19% vs. 4%) and follow-up (26% vs. 7%). Field workers experienced incident kidney injury (IKI) more frequently than other workers: 26% versus 2%, respectively. Age (ß = −0.71, 95%CI: −1.1, −0.4), current position as a field worker (ß = −2.75, 95%CI: −6.49, 0.99) and past work in construction (ß = 3.8, 95%CI: −0.1, 7.6) were included in the multivariate regression model to explain eGFR at enrollment. The multivariate regression model for decreased in eGFR over three month included current field worker (ß = −3.9, 95%CI: −8.2, 0.4), current smoking (ß= −6.2, 95%CI: −13.7−1.3), dehydration (USG ≥ 1.025) at both visits (ß= −3.19, 95%CI: −7.6, 1.2) and pain medication at follow-up (ß= −3.2, 95%CI: −8.2, 1.95). Current fieldwork [IR (incidence rate) = 2.2, 95%CI 1.1, 5.8) and being diabetic (IR = 1.8, 95%CI 0.9, 3.6) were associated with IKI. Low eGFR was common in field workers from a rice company in Guanacaste, and being a field worker was a risk factor for IKI, consistent with the hypothesis that occupational heat exposure is a critical risk factor for CKDu in Mesoamerica.

Performance of Cervical Screening a Decade Following HPV Vaccination: The Costa Rica Vaccine Trial.

BACKGROUND: We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. METHODS: A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. RESULTS: We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. CONCLUSIONS: Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.

Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults.

Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath's EAA (1.69-years; 95% CI 0.72, 2.67), Hannum's EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (- 0.04-kb; 95% CI - 0.08, - 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort.

Predictors of Secondhand Smoke Exposure During Pregnancy in Costa Rica, the Dominican Republic, and Honduras.

INTRODUCTION: Secondhand smoke (SHS) exposure poses risks to pregnant women and children. Though smoking among pregnant women in many low- and middle-income countries is low, exposure to SHS might be higher. We examined the prevalence and predictors of SHS among pregnant women from Costa Rica, the Dominican Republic, and Honduras. METHODS: Postpartum women 18+ years old who completed pregnancy in past 5 years were surveyed in health care and community settings. RESULTS: Data for 1,081 women indicated low tobacco use (1.0%-3.7%), frequent exposure to active smokers (29.0%-34.0%), often being close enough to breathe others' smoke (49.4%-66.5%), and most having smoke-free home policies (70.8%-76.2%). Women reporting unintended pregnancy (adjusted odds ratio [aOR]: 1.44, 95% confidence interval [CI] 1.03, 2.00) and alcohol consumption (aOR: 1.92, 95% CI 1.34, 2.77) were more likely to be close enough to breathe others' smoke. Women with health problems during pregnancy (aOR: 1.48 95% CI 1.07, 2.06) were more likely to have home smoking policies. Tobacco use was associated with all SHS exposure outcomes. CONCLUSIONS: SHS exposure was high during pregnancy; women with higher risk variables, that is, tobacco use, alcohol consumption, and unintended pregnancy were more likely to be exposed. Addressing SHS exposure in pregnancy in low- and middle-income countries can improve maternal health outcomes in vulnerable populations. IMPLICATIONS: The study results suggest a cluster of multiple risk factors associated with a high prevalence of exposure to SHS among pregnant women in LIMCs from Latin America and Caribbean Region. Interventions, regulations, and policies need to address specific high-risk factors to change behaviors and improve maternal and child health outcomes especially in vulnerable populations.

Social inequality in incidence and mortality of malignant neoplasms of lip, oral cavity and pharynx: Is Costa Rica an international paradox?

OBJECTIVES: Low socioeconomic position (SEP) has been associated with higher incidences and mortality of lip, oral cavity and pharynx (LOP) cancers in the vast majority of countries with available data. The origins of health inequalities in cancer are socioeconomic, although they vary by time and country. Evidence from Low-and Middle-income Countries (LMICs) remains scarce. This study aims to identify and describe socioeconomic inequalities in LOP cancers incidence and mortality in Costa Rica. The hypothesis tested is that people leaving in low-SEP districts in Costa Rica have greater incidence and mortality rates of lip, oral cavity and pharynx cancers. METHODS: The 10th revision of the International Classification of Diseases (ICD-10) was used to define cancer sites. Data come from a national population-based Cancer Registry with 100% completeness to study incidence. Incidence rate included all new cases of LOP cancer diagnosed from January 1, 2011, and December 31, 2015, for a total of 2 798 517 individuals, 13 832 524 years of follow-up and 601 LOP cases. Mortality rate was extracted from the National Death Index, including 2 739 733 individuals, 23 950 240 person-years of follow-up and 586 LOP cancer deaths, from January 1, 2010, to December 31, 2018. The 2011 Census (with 94% of Costa Rican inhabitants) was used to characterize the urbanicity and wealth of 477 districts. Survival models were performed for both incidence and mortality, allowing to consider existing competitive risks. Cox models were used for incidence, and parametric survival models based on a Gompertz distribution for mortality. RESULTS: The study found that people who lived in the most socioeconomically disadvantaged areas had lower probabilities of developing LOP cancers than people in the richest districts. The same pattern for mortality, however, was not significant. CONCLUSIONS: The hypothesis that incidence and mortality of LOP cancers will show a positive social gradient was not confirmed in this study, contradicting the existing literature. This could be explained by the social distribution of risky health behaviours, more frequent in socially advantaged populations.

Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial.

HPV vaccination of adolescent girls is the most effective measure to prevent cervical cancer. The World Health Organization recommends that adolescent girls receive two doses of vaccine but only a small proportion of girls from regions with the highest disease burden are vaccinated because of cost and logistical considerations. Our Costa Rica HPV Vaccine trial suggested that one dose of the bivalent HPV vaccine provides robust and lasting protection against persistent HPV infections for over a decade. Data from a post-licensure trial of the quadrivalent vaccine in India also suggested that a single dose may be effective in reducing cervical cancer risk. To formally compare one versus two doses of the bivalent and nonavalent HPV vaccines, we implemented a large, randomized, double-blind trial to investigate the non-inferiority of one compared to two vaccine doses in the prevention of new HPV16/18 infections that persist 6 or more months. Bivalent and nonavalent vaccines will be evaluated separately. The trial enrolled and randomized (1:1:1:1 to 1- and 2-dose arms of the bivalent and nonavalent vaccines) 20,330 girls 12 to 16 years old residing in Costa Rica. Trial participants are followed every 6 months for up to 5 years. We also aim to estimate vaccine efficacy by comparing the rates of 6 month persistent infection in unvaccinated women with the rates in the follow-up visits of trial participants. We included one survey of unvaccinated women at the start of the study (N = 4452) and will include another survey concomitant with follow up visits of trial participants at year 4.5 (planned N = 3000). Survey participants attend two visits 6 months appart. Herein, we present the rationale, design, and enrolled study population of the ESCUDDO trial. ClinicalTrials.gov Identifier: NCT03180034.

Equine infection with Leishmania spp. in Costa Rica: Study of five cases.

BACKGROUND: Cutaneous forms of leishmaniosis due to Leishmania braziliensis have been reported in horses in the New World. Domestic animals play a role in the transmission of the disease. In Costa Rica, human cases of L. braziliensis, L. panamensis and L. infantum have been reported. OBJECTIVES: The present report describes five cases of equine cutaneous leishmaniosis in Costa Rica. The aetiological diagnosis was based on the presence of the parasite within the lesions. METHODS: Skin biopsies were used to perform histopathological analyses of the lesions. Immunohistochemistry was used to detect the presence of the Leishmania spp. antigens in tissue sections. Laser-capture micro-dissection and quantitative real-time PCR techniques were carried out to detect the pathogen nucleic acid within the microscopic lesions. RESULTS: Histopathological analyses showed a granulomatous inflammation within the dermis, with multi-nucleated giant cells, macrophages, lymphocytes and few neutrophils and eosinophils. We detected the parasite by immunohistochemistry, using a rabbit polyclonal antibody raised against Leishmania spp. However, we could not identify Leishmania spp. by quantitative real-time PCR in formalin-fixed paraffin-embedded tissues, using specific primers for the conserved region in the minicircle of the Leishmania DNA kinetoplast. CONCLUSIONS: Our results emphasise the importance of Leishmania spp. not only as a causative agent of equine cutaneous disease in the New World, but also as a possible emerging pathogen. Leishmaniosis is one of the most prevalent parasitic public health problems worldwide, and equines may have a role in the epidemiology of the disease.

The TNF-A-857*T Polymorphism is Associated with Gastric Adenocarcinoma Risk in a Costa Rican Population.

BACKGROUND: Costa Rica is ranked as one of the countries with highest incidence of gastric cancer worldwide. Previous studies in Costa Rican populations have revealed associations between gastric cancer risk and several cytokine polymorphisms that seem to play a role in the regulation of the expression of these proteins. In this study, we assessed associations of the polymorphisms IL-6-174 G/C, IFNGR1-56 C/T, IL-8-251 T/A and TNF-A (-857 C/T, -308 A/G) with gastric pathologies in a high-risk population of Latin America. METHODS: DNA samples of 47 patients with gastric adenocarcinoma, 53 with chronic gastritis, 56 with duodenal ulcer and 94 healthy controls, were genotyped for the five mentioned SNPs. All participants were ≥50-years-old. Genotyping was performed by PCR-RFLP and 5'-nuclease PCR assay. H. pylori infection, CagA status, pepsinogen (PG) I and II blood levels were determined by ELISA. Logistic regression analysis was used to determine possible associations of the polymorphisms with cancer, gastritis and duodenal ulcer, and linear regression analysis to determine associations with blood PG levels. RESULTS: A total of 86.6% of the population was positive for H. pylori; of them, 51.6% was CagA+. Patients with the TNF-A-857*T allele had an increased risk for gastritis (OR: 3.67, p = 0.015) and gastric adenocarcinoma (OR:6.15, p = 0.001). Associations between other polymorphisms and gastric diseases, or PG levels, were not found. CONCLUSIONS: Our results indicate that the TNF-A-857*T SNP is among the risk factors associated with the risk of gastric cancer in Costa Rica.

The inguinal hernia management in Costa Rica according to a survey between surgeons: result comparison with 2018 International Groin Hernia Guidelines.

BACKGROUND: Inguinal hernia surgery is a frequent procedure among general surgeons in Costa Rica, but the management and technique are not uniform. The International Guideline for Groin Hernia management was published in 2018 to standardize the inguinal hernia surgery, but the diffusion of the guidelines and its adherence have been extremely varied. PURPOSE: Collect and analyze the current reality regarding groin hernia management in Costa Rica. Secondly evaluate the diffusion and development comparing it to the guideline's recommendations. METHOD: Questionnaire of 42 single and multiple answer questions according to the topics of the International Guideline directed to general surgeons. Diffusion of the inquiry through surgical and hernia association chats and email. Timeframe June-December 2019. RESULTS: 64 surveys were collected, which is a representative number of the general surgeons national college. The most frequent procedure between these was the abdominal wall surgery. Every surgeon did more than 52 groin hernia surgeries in one year, most of them outpatients. The epidural anesthesia was used the most and Lichtenstein's technique was the most frequently used (64%). 68% of the surgeons know how to perform a minimally invasive inguinal hernia surgery but with variable volumes. 38% of participants considered themselves experts in groin hernia management and 52% did not know the 2018 International Guideline. The recommendations of such guideline are followed only partially. CONCLUSIONS: The 2018 Hernia Surge International Guidelines have low diffusion among Costa Rican surgeons. The laparoscopic approach is widely accepted but there are no studies to assess the results and the quality. There should be protocols and studies adapted to Costa Rica's national situation.