Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala.

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk.

Tuberculosis (TB) disease still kills 1-person every 21-seconds. Few TB diagnostic tests are considered truly appropriate for point of care settings. The WHO-endorsed immunodiagnostic Alere Determine Lipoarabinomannan Ag-test (LAM-test) detects Mycobacterium tuberculosis complex LAM in urine, and its use is recommended for TB diagnosis among HIV co-infected individuals with low CD4 T-cell counts. Here we found that a simple 15-minute enzymatic treatment at room temperature of LAM-spiked urine with α-mannosidase (for human TB), and LAM-spiked milk with combined lactase and caseinase (for bovine TB), enhanced 10-fold the detection levels of the LAM-test and thus, improved the detection of LAM by the LAM-test in urine and milk that otherwise could be missed in the field. Future separate clinical research studies specifically designed to address the potential of these findings are required.

Late Presentation and Missed Opportunities for HIV Diagnosis in Guatemala.

Early HIV diagnosis remains a challenge in many regions with delayed diagnosis resulting in increased morbidity and mortality. We conducted a retrospective cohort study of people living with HIV receiving outpatient care at a large tertiary referral center in Guatemala to describe the proportion of late presenters (LP) and missed opportunities for HIV diagnosis. Of 3686 patients, 2990 (81.1%) were LP who were more likely to be male (60.2% vs. 48.0%, p < 0.0001), heterosexual (88.0% vs. 78.0%, p < 0.0001) and rural dwellers (43.7% vs. 33.8%. p < 0.0001). The proportions of patients who presented late or with AIDS at diagnosis decreased over time. Only 665 patients (18.2%) sought care in the 2 years prior to HIV diagnosis. This study, the first of its kind in Central America to focus on late presenters and missed opportunities for HIV diagnosis, demonstrates extremely high rates of LP in Guatemala. Although in recent years rates of LP have improved somewhat, the need for screening outside of traditional healthcare settings is apparent.

Evolutionary history and spatiotemporal dynamics of the HIV-1 subtype B epidemic in Guatemala.

Different explanations exist on how HIV-1 subtype B spread in Central America, but the role of Guatemala, the Central American country with the highest number of people living with the virus, in this scenario is unknown. We investigated the evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala. A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naïve, HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined with published subtype B sequences from other Central American countries (n = 2,101) and with reference sequences representative of the BPANDEMIC and BCAR lineages from the United States (n = 465), France (n = 344) and the Caribbean (n = 238). Estimates of evolutionary, demographic, and phylogeographic parameters were obtained from sequence data using maximum likelihood and Bayesian coalescent-based methods. The majority of Guatemalan sequences (98.9%) belonged to the BPANDEMIC clade, and 75.2% of these sequences branched within 10 monophyletic clades: four also included sequences from other Central American countries (BCAM-I to BCAM-IV) and six were mostly (>99%) composed by Guatemalan sequences (BGU clades). Most clades mainly comprised sequences from heterosexual individuals. Bayesian coalescent-based analyses suggested that BGU clades originated during the 1990s and 2000s, whereas BCAM clades originated between the late 1970s and mid 1980s. The major hub of dissemination of all BGU, and of BCAM-II, and BCAM-IV clades was traced to the Department of Guatemala, while the root location of BCAM-I and BCAM-III was traced to Honduras. Most Guatemalan clades experienced initial phases of exponential growth (0.23 and 3.6 year-1), followed by recent growth declines. Our observations suggest that the Guatemalan HIV-1 subtype B epidemic is driven by dissemination of multiple BPANDEMIC founder viral strains, some restricted to Guatemala and others widely disseminated in the Central American region, with Guatemala City identified as a major hub of viral dissemination. Our results also suggest the existence of different sub-epidemics within Guatemala for which different targeted prevention efforts might be needed.

Novel HLA class I associations with HIV-1 control in a unique genetically admixed population.

Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman's rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.

Staphylococcus aureus bloodstream infections in Latin America: results of a multinational prospective cohort study.

BACKGROUND: Substantial heterogeneity in the epidemiology and management of Staphylococcus aureus bacteraemia (SAB) occurs in Latin America. We conducted a prospective cohort study in 24 hospitals from nine Latin American countries. OBJECTIVES: To assess the clinical impact of SAB in Latin America. PATIENTS AND METHODS: We evaluated differences in the 30 day attributable mortality among patients with SAB due to MRSA compared with MSSA involving 84 days of follow-up. Adjusted relative risks were calculated using a generalized linear model. RESULTS: A total of 1030 patients were included. MRSA accounted for 44.7% of cases with a heterogeneous geographical distribution. MRSA infection was associated with higher 30 day attributable mortality [25% (78 of 312) versus 13.2% (48 of 363), adjusted RR: 1.94, 95% CI: 1.38-2.73, P < 0.001] compared with MSSA in the multivariable analysis based on investigators' assessment, but not in a per-protocol analysis [13% (35 of 270) versus 8.1% (28 of 347), adjusted RR: 1.10, 95% CI: 0.75-1.60, P = 0.616] or in a sensitivity analysis using 30 day all-cause mortality [36% (132 of 367) versus 27.8% (123 of 442), adjusted RR: 1.09, 95% CI: 0.96-1.23, P = 0.179]. MRSA infection was not associated with increased length of hospital stay. Only 49% of MSSA bloodstream infections (BSI) received treatment with ß-lactams, but appropriate definitive treatment was not associated with lower mortality (adjusted RR: 0.93, 95% CI: 0.70-1.23, P = 0.602). CONCLUSIONS: MRSA-BSIs in Latin America are not associated with higher 30 day mortality or longer length of stay compared with MSSA. Management of MSSA-BSIs was not optimal, but appropriate definitive therapy did not appear to influence mortality.

Optimización de recursos para determinar la carga viral de HIV-1 en un país con pocos recursos / Optimizing resources to reduce costs to determine HIV viral load in limited resources settings

Resumen Introducción. Las metas globales para controlar la epidemia de HIV contemplan que la carga viral sea indetectable en 90 % de las personas en tratamiento. El costo de la medición de la carga viral en lotes de muestras puede reducirse y, así, aumentar la cobertura cuando los recursos son limitados; sin embargo, su eficacia disminuye al aumentar la prevalencia del fracaso del tratamiento antirretroviral. Objetivo. Evaluar estrategias para disminuir la proporción de pacientes con fracaso del tratamiento antirretroviral en los lotes de muestras y, de esta manera, aumentar el ahorro en las pruebas de carga viral. Materiales y métodos. Las estrategias evaluadas fueron: a) la organización de los lotes de muestras según el esquema de tratamiento antirretroviral, y b) la exclusión de aquellos pacientes con antecedente reciente de fracaso del tratamiento antirretroviral, aquellos con menos de 12 meses de tratamiento antirretroviral y aquellos sin tratamiento antirretroviral previo. Los resultados de los lotes se compararon con los resultados individuales. Resultados. El valor diagnóstico negativo fue similar para los pacientes con esquema de primera línea (100,0 %; IC95% 99,5-100,0) o de segunda línea de tratamiento (99,4 %; IC95% 96,9-99,9). La incidencia del fracaso del tratamiento antirretroviral fue menor en los pacientes con tratamiento de primera línea (p<0,01), lo cual permitió un mayor ahorro en las pruebas de laboratorio en este grupo (74,0 %; IC95% 71,0-76,7) que en los pacientes con tratamiento de segunda línea (50,9 %; IC95% 44,4-57,3) (p<0,01). Conclusión. La selección de las muestras que se incluyeron en los lotes para determinar la carga viral del HIV según el tipo de esquema de tratamiento, permitió maximizar el porcentaje de ahorro en pruebas de laboratorio.

Abstract Introduction: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. Objective: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. Materials and methods: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. Results: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapypatients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). Conclusion: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.

A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries.

Staphylococcus aureus is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185 S. aureus) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec [SCCmec] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCCmec IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.

Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection.

OBJECTIVE: Long-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP. METHODS: We analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission. RESULTS: Reverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time. CONCLUSIONS: Results illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.

Identification of major routes of HIV transmission throughout Mesoamerica.

BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location. RESULTS: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico. CONCLUSION: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.

[Optimizing resources to reduce costs to determine HIV viral load in limited resources settings].

INTRODUCTION: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. OBJECTIVE: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. MATERIALS AND METHODS: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. RESULTS: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). CONCLUSION: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.

AIDS-Defining Illnesses at Initial Diagnosis of HIV in a Large Guatemalan Cohort.

BACKGROUND: Anecdotal evidence suggests that a high proportion of patients diagnosed with HIV in Guatemala present with AIDS. There remain limited data on the epidemiology of AIDS-defining illnesses (ADIs) in Central America. METHODS: We conducted a retrospective cohort study of all patients living with HIV at the largest HIV clinic in Guatemala. Charts were analyzed for clinical and demographic data. Presence of an ADI was assessed by US Centers for Disease Control definitions; patients who presented with an ADI were compared with those without ADI using descriptive statistics. RESULTS: Of 3686 patients living with HIV, 931 (25.3%) had an ADI at HIV diagnosis, 748 (80.3%) of whom had CD4 counts lower than 200 cells/mm3. Those with ADIs were more likely to be male (67.5% vs 54.6%; P < .0001) and heterosexual (89.4% vs 85.0%; P = .005). The most common ADIs were Mycobacterium tuberculosis (55.0%), Pneumocystis jirovecii pneumonia (13.7%), esophageal candidiasis (13.4%), and histoplasmosis (11.4%). Histoplasmosis and HIV wasting syndrome were both more common among rural patients. CONCLUSIONS: In this large Guatemalan cohort of patients currently living with HIV, a significant portion presented with an ADI. These data inform the most common ADIs diagnosed among survivors, show that histoplasmosis is more commonly diagnosed in rural patients, and suggest that HIV wasting syndrome may reflect missed histoplasmosis diagnoses.

Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.

INTRODUCTION: Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. METHODS: Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. RESULTS: A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1-13.7; p < 0.001) were independently associated with in-hospital mortality. CONCLUSIONS: This study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on prevention and control of CPE BSI.

La Cascada de la adherencia a la atención integral al tratamiento antirretroviral en Guatemala y factores institucionales que influyen en su evaluación / The Cascade of the integral attention to the treatment antiretroviral treatment in Guatemala and institutional factors that influence your evaluation

Introducción: La implementación de la terapia antirretroviral (TAR) en Centroamérica ha tenido un desarrollo diferente en cada país. En Guatemala en la última década, se ha ampliado sus coberturas de manera importante y por el apoyo inicial de Médicos sin Fronteras y luego con los Recursos del Fondo Mundial de Lucha contra el Sida, Malaria y Tuberculosis, y el progresivo aumento de la inversión por parte del Ministerio de Salud y el Seguro social, el acceso al TAR es una realidad. Sin embargo, con los conceptos de acceso universal al diagnóstico y tratamiento, y buscando llegar a los estándares propuestos por la Cascada o Continuum de Adherencia a la Atención integral y el TAR, una evaluación de su estado actual, se hizo necesaria. Objetivos: Desarrollar un diagnóstico de situación del estado de la adherencia al tratamiento ARV y establecer los componentes de la cascada de atención, relacionados con la adherencia en Guatemala. Métodos: Como parte Proyecto CAMPLUS y con la coordinación de Proyecto Capacity-USAID Guatemala, con expertos locales, se desarrolló una guía para establecer el cumplimiento de TAR, utilizando la carga viral y para documentar la cascada de adherencia al tratamiento del VIH, en Guatemala...(AU)

Morbi-mortalidad en pacientes con infección por Mycobacterium tuberculosis comprobada, y co-infección VIH-Tuberculosis en Hospital Roosevelt en Guatemala / Morbi-mortality in patients with proved Mycobacterium tuberculosis infections, co-infected and no co-infected with HIV, at Roosevelt Hospital in Guatemala

Tuberculosis (TB) es la enfermedad oportunista más importante relacionada con VIH, provocando manifestaciones clínicas graves y con frecuencia diseminadas, y afección extrapulmonar. En Guatemala es la principal causa de muerte en pacientes con Sida. OBJETIVO: Determinar la morbi-mortalidad en pacientes hospitalizados con Tuberculosis en Hospital Roosevelt. MÉTODOS: Se incluyeron pacientes con diagnóstico comprobado por tests microbiológicos positivos para Mycobacterium tuberculosis, mayores de 12 años de edad, ingresados en los servicios de Medicina interna durante el año 2013. Se consideraron positivos los pacientes con frotes de ZN, prueba de PCR-RT (GeneXpert de Cepheid). Se colectaron los datos clínicos y epidemiológicos de los pacientes con un instrumento estandarizado de manera prospectiva, generándose una base de datos en Excel 2010 y realizando el análisis estadístico con: SPSS21...(AU)

Introduction: Tuberculosis (TB) is the main opportunistic infection related to HIV, causing complex and serious disease, frequently, extra-pulmonary in HIV patients. In Guatemala it represents the main cause of death in AIDS patients and with an increased incidence in patients with other co-morbidities. OBJECTIVE: To determine the morbi-mortalily in admitted patients in internal medicine wards with tuberculosis at Roosevelt Hospital in Guatemala City. METHODOLOGY: Patients with proved infection by clinical and/or culture/PCR-RT positive to Mycobacterium tuberculosis were included, older than 12 years old, admitted to the internal medicine guards, which presented positive culture and/or ZN smears and/or PCR-RT (GeneXpert, Cepheid) positive tests in 2013. Clinical and epidemiological data were collected in a prospective manner, with a standardized instrument, generating an Excel 2010 data base that was analyzed by SPSS21. RESULTS: 200 patients were included, 61% males with man: woman ratio of 1.5:1. 48% presented HIV coinfection. 54% of the patients aged: 25 to 44 years old. 43% residents outside Guatemala City. The extra pulmonary TB was present in 65%. The highest mortality was observed in TB-HIV co-infected patients: 30.2% versus 10. % in lung cases (p=0.001). 2.1% died in the first 24 hours after admission, 13.5% between 1-7 days; 14.6% after 7 days of hospital stay, (p=0.002). Regarding the CD4 count, the higher mortality index was shown in the cases <100cel/mL 28.12%, versus 2.08% in > 100 (p=0.0001). CONCLUSSIONS: In a reference center like Roosevelt Hospital, the coinfection HIV-TB represents 48% of the TB cases. Mortality was higher in extrapulmonary TB and HIV patients with <100 CD4 counts

Caracterización clínica y epidemiológica de pacientes con bacteriemia en la Unidad de Cuidados Intensivos de Medicina Interna y Cirugía. Hospital Roosevelt-Guatemala / Clinical and epidemiological characterization of patients with bacteremia in the Intensive Care Unit of Internal Medicine and Surgery. Roosevelt Hospital-Guatemala

Antecedentes: La bacteriemia constituye un problema de salud prioritario debido al obstáculo que impone al proceso curativo de los pacientes, involucrando al personal y a los sistemas de salud. Objetivo: Caracterizar clínica y epidemiológicamente pacientes con bacteriemia. Materiales y Métodos: Se realizó una revisión retrospectiva de pacientes con hemocultivos positivo del año 2013, en el Intensivo médico-quirúrgico, del Hospital Roosevelt, con instrumento estandarizado, que incluyó: datos demográficos, morbilidades, comorbilidades, registro de morbilidad y mortalidad. Se calcularon intervalos de confianza al 95% y odds ratio (OR). Resultados: De 47 expedientes y 87 hemocultivos, 55% fueron femeninos, con predominio de edad de 30-49 años, en su mayoría, amas de casa. El 49%, presentó una o más condiciones médicas asociadas. La mayoría de casos de bacteriemia fueron asociados a cuidados de salud, de origen secundario. El principal foco infeccioso fue respiratorio. Los principales microorganismos aislados fueron A. baumannii, K. pneumoniae y S. haemolyticus. Los procedimientos invasivos más frecuentes fueron uso de catéter venoso central y periférico. La tasa de letalidad al día 14 fue del 30%. Conclusiones: Se observó predominio de bacteriemias secundarias, asociadas a los cuidados de la salud, cuyos principales microorganismos aislados coinciden con literatura internacional. La mayor mortalidad fue observada en el sexo femenino.(AU)

Background: Bacteremia known as a major public health problem, because of the limitation it causes to the healing process among patients, involving both health care workers, and health system.Objectives: Characterize the clinical and epidemiological profile among patients with bacteremia.Materials and methods: A retrospective review was made, including positive blood culture patients, admitted to the medical and surgical Intensive Care Unit during 2013, with a standardized instrument which included: demographical data, morbidities and co-morbidities, including a morbidity and morta-lity. The statistics included 95% confidence intervals and odds ratio (OR).Results: Of 47 clinical files, 87 blood cultures, 55% were females. The mostly affected age group was the one within 30-49 years, mainly housewives. 49% presented one or more than one associated con-dition. Most cases of bacteremia were secondary, nosocomial and health care associated. The main origin was the respiratory tract. Main microorganisms isolated were A. baumannii, K. pneumoniae and S. haemolyticus. The most frequent invasive dispositive was central and peripheral venous catheteri-zation. The mortality rate at day 14 was 30%.Conclusions: A predominance of secondary bacteremia, health care associated was observed, who-se main isolated microorganisms agree with international literature. The highest mortality rate was observed in the female sex (AU)

HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p<0.001), followed by nucleoside RT inhibitors (1.8%) and protease inhibitors (1.0%). No significant trends in PDR prevalence were observed during the study period. However, higher NNRTI PDR levels were found in individuals with >500 and 350-500 CD4(+) T cells/µl (7.4% and 8.7%, respectively) compared to individuals with <350 CD4(+) T cells/µl (3.7%; p=0.039 and p=0.007, respectively), as well as a tendency of higher levels of NNRTI transmitted drug resistance (DR) in individuals with recent infection determined by HIV incidence tests (9.7%), suggesting increasing trends in time. Clusters of viruses with NNRTI PDR suggesting complex transmission networks were observed. No associations between PDR and demographic variables were found. PDR in Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.

Los experimentos de Sífilis y otras infecciones de transmisión Sexual en Guatemala, 1946-1948, ¿un dilema ético y político para Guatemala y el mundo? / The experiments of Syphilis and other sexually transmitted infections in Guatemala, 1946-1948, an ethical and political dilemma for Guatemala and the world?

En Guatemala se llevaron a cabo experimentos por entidades de salud de Estados Unidos de Norte América, inoculando infecciones de transmisión sexual (gonorrea, sífilis y cancroide) a poblaciones vulnerables con el objetivo de generar un modelo humano para estudio de este tipo de enfermedades. Estos experimentos permanecieron ocultos durante 64 años, cuando la Dra. Susan Reverby los descubrió al revisar los archivos de quien fuera el investigador de los mismos, Dr. John C. Cutler. Fueron inoculados 1308 personas y reportadas fallecidas 83. Al hacerse pública esta nefasta noticia, se condenaron los hechos acontecidos entre 1946-1948 por múltiples organizaciones y el gobierno, nombrándose una Comisión Presidencial en Guatemala y por su parte el gobierno de Estados Unidos también conformó una Comisión Presidencial. Los informes y dictámenes de ambas Comisiones coinciden en que se violaron los principios éticos y morales, que la desigualdad social y racismo existente en esa época fueron condicionantes muy importantes, que lo acontecido puede ser catalogado como crímenes de lesa humanidad y que las personas que planificaron, aprobaron, condujeron, facilitaron y financiaron estos experimentos son moralmente culpables. A la fecha no se ha otorgado ningún resarcimiento a los afectados o familiares, ni compensación alguna a Guatemala...(AU)

In Guatemala, experiments were carried out by health entities in the United States of America, inoculating sexually transmitted infections (gonorrhea, syphilis and canker) into vulnerable populations with the aim of generating a human model for the study of this type of disease. These experiments remained hidden for 64 years, when Dr. Susan Reverby discovered them by reviewing the files of whoever was their researcher, Dr. John C. Cutler. 1308 people were inoculated and 83 were reported deceased. When this ominous news was made public, the events occurred between 1946-1948 by multiple organizations and the government were condemned, a Presidential Commission was appointed in Guatemala and for its part the government of the United States also formed a Presidential Commission. The reports and opinions of both Commissions agree that ethical and moral principles were violated, that the social inequality and racism that existed at that time were very important conditions, that what happened can be classified as crimes against humanity and that the people who planned , approved, conducted, facilitated and financed these experiments are morally culpable. To date no compensation has been granted to those affected or relatives, nor any compensation to Guatemala ... (AU)