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.

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.

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.

Alteraciones del sedimiento urinario en pacientes con VIH y correlación con biopsia renal / Urinary sediment alterations in HIV patients and correlated with renal biopsy

Hasta 30% de pacientes con VIH pueden desarrollar algún tipo de enfermedad renal y tienen mayor riesgo de desarrollar insuficiencia renal que las personas sin VIH. Material y métodos: Se realizó un estudio descriptivo, prospectivo en pacientes atendidos en la clínica de enfermedades infecciosas del Hospital Roosevelt realizando un examen simple de orina al azar y en los pacientes con alteraciones urinarias, el índice albumina creatinina, para establecer el rango de proteínas y de esta manera valorar toma de biopsia para establecer el tipo de nefropatía existente. Resultados: Se incluyeron 356 pacientes de un total de 2400, con una incidencia de alteraciones del sedimento urinario de 7 %, la presencia de proteinuria se presentó más frecuentemente en pacientes que reciben tratamiento antirretroviral en combinación con tenofovir con un porcentaje de 11.5 en comparación con...

Factores de riesgo cardiovascular en pacientes con virus de inmunodeficiencia humana en Guatemala / Cardiovascular risk factors in patients with human immunodeficiency virus in Guatemala

Objetivo: Determinar la prevalencia de factores de riesgo cardiovascular en una cohorte de pacientes infectados con el virus de inmunodeficiencia humana recibiendo terapia antirretroviral de gran actividad. Material y Métodos: Se realizó un estudio transversal con 300 pacientes que asistieron a la consulta externa/ambulatoria de la Clínica de Enfermedades Infecciosas del Hospital Roosevelt de la ciudad de Guatemala, entre los meses de septiembre y noviembre de 2009...

Costo del tratamiento de infecciones nosocomiales por gérmenes multirresistentes, Hospital Roosevelt, Guatemala / Cost of treatment of nosocomial infections by multiresistant pathogens, Roosevelt Hospital, Guatemala

Este estudio tuvo por objeto determinar el impacto económico del tratamiento de infecciones graves por bacterias resistentes en unidades de cuidados intensivos del Hospital Roosevelt de la ciudad de Guatemala. Se aplicó el método de casos y controles para cuantificar el impacto económico del tratamietno de infecciones graves producidas por los siguientes microorganismos resistentes a los antibióticos: Staphylococcus aureus resistente a la meticilina (SAMR), Pseudomonas aeruginosa y Acinetobacter baummani resistentes a imipenem...

Métodos diagnósticos para hepatitis viral / Diagnostic methods for viral hepatitis

El uso correcto de los métodos serológicos disponibles para el diagnóstico correcto de las Hepatitis Virales, nos permite evaluar su evolución, su seguimiento y aún su respuesta al tratamiento en el caso de Hepatitis Crónica como la Hepatitis B. Los conocidos paneles de diagnóstico de Hepatitis Viral, deben ser analizados en el contexto de la evaluación de cada caso clínico en particular. Siendo así debemos considerar que para la evaluación de un caso de hepatitis viral aguda, los marcadores serológicos que nos pueden ayudar a establecer la etiología de la misma en más del 80/100 de los casos, va dirigida a investigar la presencia de anticuerpos IgM contra el virus de la hepatitis A y el Anticore IgM de hepatitis B así como el HBsAg. No se requiere de rutina en la evaluación inicial la detección del virus de la hepatitis C...

Consenso de diagnóstico y tratamiento de la hepatitis / Consensus on the diagnosis and treatment of viral hepatitis

El tratamiento de las hepatitis virales es motivo de muchas conductas terapéuticas basadas en tradiciones médicas y populares que carecen de documentación que las respalde. La mayoría de las hepatitis virales agudas son explicadas por los virus de la hepatitis A y de la hepatitis B. Otras formas de hepatitis como la C y la D están relacionadas con situaciones específicas en la mayoría de los casos. Por ejemplo, la hepatitis C está relacionada con antecedentes de transfusiones de sangre y hemoderivados, en tanto que la hepatitis Delta es endémica en ciertas áreas como la Mediterránea, y la cual, para producirse requiere de la presencia del virus de la hepatitis B para replicarse...

Resistencia bacteriana en bacilos gram-negativo aerobios en el Hospital Roosevelt / Aerobic Gram-negatives and bacterial resistance in Hospital Roosevelt

Objetivo: Establecer las tasas de resistencia antimicrobiana de los bacilos Gram negativo aerobios en el Hospital Roosevelt, como base para un mecanismo de vigilancia a largo plazo.Metodología: En un período de 6 meses consecutivos (marzo-septiembre 1996) fueron colectadas 796 cepas de bacilos Gram-negativos:E. coli (223), Pseudomonas aeruginosa (139), Acinetobacter baumannii(100),Klebsiella pneumoniae (86)Klebsiella oxytoca (57), Enterobacter aerógenas (46),Enterobacter cloacae (46), Proteus mirabilis (39) y otros (52).Se realizaron pruebas de susceptibilidad invitro por la técnica de Bauer y Kirby de difusión en disco de forma estandarizada contra 20 antimicrobianos, según especificaciones del NCCLS de USA.Resultados: se encontró >90/100 de susceptibilidad de E. coli a Cefalosporinas de 3a.generación, pero ya 18/100 de resistencia a Quinolonas y 58/100 de resistencia a Trimetoprim-sulfa. La sensibilidad a Carbapenems y Piperalicilina-Tazobaltam fue muy buena:97/100-100/100. Para Pseudomonas se encontró 73/100 de sensibilidad a Ceftazidima, 82/100 a Amikacina, 82/100 a Ciprofloxacina y m s de 90/100 a Carbapenems y Piperacilina-Tazobactam, 89/100 de Acinetobacter baumannii sensible a Carbapenems, 72/100 a Piperacilina-Tazobactam y 74/100 a Ciprofloxacina. Es interesante 60/100 de Cepas de Kleibsiella pneumoniae son sensibles a Trimetroprim Sulfa.Conclusión: Los Carbapenems y Piperacilina-Tazobactam son útiles contra la mayoría de infecciones producidas por bacilos Gram-Negativo. Un grado apreciable de resistencia 18-26/100 se observa a las Quinolonas. La sensibilidad de bacterias coliformes a Cefalosporinas de 3a. generación sigue siendo adecuada. Una vigilancia regular es requerida en las instituciones para dirigir mejor su terapeútica