Clinical characteristics, diagnosis, treatment and outcomes of patients living with HIV and co-infected with tuberculosis and histoplasmosis: a 5-y retrospective case series.

BACKGROUND: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. METHODS: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. RESULTS: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%. CONCLUSIONS: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.

Diagnostic Mycology Laboratories Should Have a Central Role for the Management of Fungal Disease.

The absence of awareness of fungal diseases as part of the differential diagnosis in at-risk populations has severe consequences. Here, we show how the active role of laboratories can improve patients' survival. Recently, major advances have been made in non-culture-based assays for fungal diseases, improving accuracy and turnaround time. Furthermore, with the introduction of proficiency control systems, laboratories are an easily monitored environment with good analytical accuracy. Diagnostic packages for opportunistic infections can overcome many deficiencies caused by the absence of awareness. In Guatemala, to make diagnosis accessible, we set up a diagnostic laboratory hub (DLH) providing screening for cryptococcosis, histoplasmosis and tuberculosis to a network of 13 healthcare facilities attending people living with HIV (PLWHIV). In two years, we screened 2127 newly HIV-diagnosed patients. The frequency of opportunistic infections was 21%, rising to 30.3% in patients with advanced HIV disease (<200 CD4); 8.1% of these patients had more than one infection. With the implementation of this diagnostic package, mortality decreased by 7%, a key goal of many public health interventions. Screening for serious infection in high-risk populations can partially overcome training or experiential deficiencies among clinicians for life-threatening fungal diseases.

Epidemiology and Mortality of Cryptococcal Disease in Guatemala: Two-Year Results of a Cryptococcal Antigen Screening Program.

Cryptococcal disease is an important opportunistic infection among people living with HIV. The cryptococcal antigen (CrAg) can be detected before the clinical onset of meningitis and its screening is recommended. Here, we evaluated CrAg frequency, and describe the epidemiological characteristics and mortality at 180 days in a cohort of HIV patients from Guatemala. A total of 3457 patients were screened with a CrAg lateral flow assay in serum between January 2017 and December 2018. CrAg positivity was 11.5% in patients with ≤100 CD4/mm3, 8.7% in patients with <200 CD4/mm3, and 6.3% in patients with <350 CD4/mm3. In Latin America, we estimated 9.2% CrAg positivity (IC95% 7.9−10.7%) in patients with ≤100 CD4/mm3. Among patients newly diagnosed with HIV, we estimated 4416 incident cases per year in Latin America in those with <200 CD4/mm3 and 5289 in those with <350 CD4/mm3. In addition, we calculated the burden in people not on ARV or without viral suppression and found 28,672 cases. CrAg screening should be considered in patients who have a CD4 cell count < 350 cells/mm3. Cryptococcal meningitis was associated with 30.8% mortality in Guatemala. Global access to diagnosis as well as to liposomal amphotericin B and flucytosine is a priority.

Impact of the COVID-19 pandemic on HIV care in Guatemala.

OBJECTIVES: To describe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the diagnosis of human immunodeficiency virus (HIV) and deaths from opportunistic infections in Guatemala. METHODS: A retrospective study was conducted to investigate the impact of the COVID-19 pandemic on people with HIV at a referral clinic (Clinica Familiar Luis Angel García, CFLAG), as well as the disruption of services at a diagnostic laboratory hub (DLH) which provides diagnosis for opportunistic infections to a network of 13 HIV healthcare facilities. Comparative analysis was undertaken using the months March-August from two different time periods: (i) pre-COVID-19 (2017-2019); and (ii) during the COVID-19 period (2020). RESULTS: During the COVID-19 period, 7360 HIV tests were performed at Clinica Familiar Luis Angel García, compared with an average of 16,218 tests in the pre-COVID-19 period; a reduction of 54.7% [95% confidence interval (CI) 53.8-55.4%],Deaths from opportunistic infections at 90 days were 10.7% higher in 2020 compared with 2019 (27.3% vs 16.6%; P = 0.05). Clinical samples sent to the DLH for diagnosis of opportunistic infections decreased by 43.7% in 2020 (95% CI 41.0-46.2%). CONCLUSION: The COVID-19 pandemic is having a substantial impact on HIV care in Guatemala. Diagnostic services for HIV have been severely affected and deaths from opportunistic infections have increased. The lessons learnt must guide the introduction of strategies to reduce the impact of the pandemic.

A Rapid Screening Program for Histoplasmosis, Tuberculosis, and Cryptococcosis Reduces Mortality in HIV Patients from Guatemala.

Opportunistic infections (OIs) and advanced HIV disease (AHD) contribute to HIV-related mortality. Here, we analyzed the situation of AHD and OIs in a cohort of newly diagnosed HIV patients from Guatemala. We included 2127 adult patients from 13 facilities across the country during 2017 to 2018. Patients were screened for tuberculosis (TB), nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcal disease, independently of their CD4 cell count. Of the 2127 enrolled patients, 1682 (79.1%) had a CD4 cell count available; of which 52% presented with AHD. Of the Mayan population, 65% had AHD. The overall OI incidence was 21%. Histoplasmosis was the most frequent OI (7.9%), followed by TB (7.1%); 94.4% of these infections occurred in patients with a CD4 < 350 cells/mm3. Mortality at 180 days was significantly higher in those with OIs than without OIs (29.7% vs. 5.9%, p < 0.0001). In one year, this program decreased the OI mortality by 7% and increased the OI treatment by 5.1%. Early OI diagnosis and appropriate therapy reduced OI mortality among newly diagnosed HIV patients in Guatemala. Screening for OIs should be considered in all newly diagnosed HIV patients who have a CD4 cell count < 350 cells/mm3 or those without a CD4 cell count available. To improve results, interventions such as early HIV detection and access to flucytosine and liposomal amphotericin B are required.

Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV.

OBJECTIVES: We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories. METHODS: The following diagnostic techniques were analyzed in 24 months (2017-2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests. RESULTS: A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89-95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89-96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3-98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen. CONCLUSION: Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries.

Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal Histoplasma galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of H. capsulatum Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of Histoplasma galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

Is Expanded HIV Testing Associated with Earlier HIV Diagnosis? Results from an HIV Clinic in Guatemala City.

BACKGROUND: Most patients in Guatemala are diagnosed with advanced HIV disease. Patients that present late in the disease process may miss the morbidity and mortality benefits associated with early treatment and may unknowingly spread HIV to others. RESEARCH QUESTIONS: We examined trends in HIV detection and levels of immunosuppression at diagnosis from 2005 -2012 to determine if expanded HIV testing was associated with earlier detection of HIV. SETTING: This study was conducted at the Clínica Familiar Luis Ángel García (CFLAG), a major HIV center associated with one of Guatemala's two national hospitals. HIV testing expanded rapidly after 2007 due to grants from the Global Fund which allowed for routine prenatal testing. METHODS: This study examined existing hospital and clinic databases from to evaluate results from HIV tests performed, and baseline CD4 cells/mm(3) on all patients newly diagnosed with HIV infection from 2005 to 2012. RESULTS: We found a decline in the number of HIV positive tests over the study period despite an increase in the total number of tests performed. Sixty-two percent of HIV infected individuals had AIDS at diagnosis. We observed a decrease in median CD4 cells/mm(3) among the prenatal testees and no change in non-prenatal testees. DISCUSSION: Expanded HIV counseling and testing services in our clinic did not result in earlier HIV diagnosis.