Diagnosis of fungal opportunistic infections in people living with HIV from Guatemala and El Salvador.

OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy, are not optimal; however, antigen (Ag) tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis. METHODS: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and Ag test. RESULTS: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analysed in this study, 94 (59%) were diagnosed using only an Ag assay. CD4 cell count data were available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200; and 90 (66%) had counts <50 CD4 cells per µl. Antiretroviral therapy utilisation at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs. CONCLUSION: More than half of the patients in this study were diagnosed only by rapid laboratory Ag tests. A high per cent of the patients had advanced HIV disease.

Implementation of rapid diagnostics assays for detection of histoplasmosis and cryptococcosis in central american people living with HIV.

OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. METHODS: Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). RESULTS: A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n = 1,343) or cryptococcosis (n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n = 170). CONCLUSION: Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.

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.