The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala

Abstract

Background A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). Methods Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. Results In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200–350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. Conclusions The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.

Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture

“…There have been many recent commercial developments in nonculture diagnostics allowing immediate or within-24-h diagnosis for the most lethal infections, including cryptococcal, Aspergillus and Histoplasma antigen, Aspergillus antibody, and PCR tests for Candida , Pneumocystis , Aspergillus , Mucormycetes, and dermatophyte infections ( 62 ). Real-life experience of these tests, either singly or collectively, has demonstrated the individual and public health merits of such testing in many different clinical settings ( 63 – 67 ). Integration of these tests into routine care pathways in high-risk patient groups requires a major shift in thinking and allocation of health care resources ( 68 ).…”

Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients

“…isolation in patients' samples. The case reports describe infection cases [116][117][118][119][120][121][122][123][124][125][126], but for several prospective and retrospective studies either it is not clear, or both infection and colonization are present [71,120,[127][128][129][130][131][132]. There is evidence that coinfection by fungal and mycobacterial spp.…”

“…Retrospective and prospective studies, mainly monocentric, have been designed to answer different questions related to NTM/ fungi coinfection. Providing evidence that these opportunistic pathogens could be isolated from sputum is either the most frequent, or a starting point for others [71,127,128,[130][131][132][135][136][137][138][139]. Comparing the results from different studies is not straightforward due to differences in study designs and studied populations.…”

“…Comparing the results from different studies is not straightforward due to differences in study designs and studied populations. For instance, Samayoa and colleagues aimed at evaluating the incidence and mortality of tuberculosis, histoplasmosis and cryptococcosis in HIV patients, with the identification of NTM and fungi coinfection as a side result [131]. An attempt to identify risk factors for coinfection in patients with specific clinical conditions was made [132,138,139].…”

Introductory Chapter: The Global Distribution of Human Histoplasmosis - An Overview

“…In Brazil, AIDS-associated disseminated histoplasmosis had a mortality as high as 33.1% [27]. In Guatemala, 31.2% of patients with advanced HIV had histoplasmosis [33].…”