Background: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283₂₂₀SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283₂₂₀SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH–proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3–35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56–76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6–74.4). In 10.5% of the PDH–proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH. Histoplasmosis is an endemic mycosis in many regions of Latin America. In the HIV population it manifests as progressive disseminated histoplasmosis (PDH), an entity hard to diagnose since the causative fungi—Histoplasma capsulatum—is slow growing and requires advance biosafety for its handling. As an alternative, the diagnosis can be made by detecting the histoplasma urinary antigen, but only one kit is commercially available outside the US. We evaluated this kit (IMMY ALPHA Histoplasma EIA) among HIV patients with suspected and found a high specificity but low sensitivity (i.e., a positive histoplasma urine antigen is almost unequivocal, but a negative result does not rule out the PDH). However, we believe the test is useful since the positive likelihood rates show that a patient with PDH is 27 times more likely to have an IMMY-HUAg positive result; this may allow early targeted treatment.

During a viral infection, the immune response is mediated by the toll-like response and myeloid differentiation Factor 88 (MyD88), who play an important role sensing infections such as SARS-CoV-2 who has claimed the lives of more than 6.8 million people around the world. We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio=1.98 (95% IC= 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG+GG vs. AA), we observed an Odd Ratio =1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio =2.44 (95% CI = 1.21-4.9) with deceased outcomes. To our knowledge this work represents an innovator report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Introduction: Noma is an opportunistic polymicrobial infection that cause necrosis of the mouth and face, with high morbidity and mortality, predominantly affecting malnourished children and persons with debilitating diseases. Cases of noma-like disease in adults, although rare, have been increasingly reported in HIV/AIDS patients particularly in developing countries but also in more developed countries. Methodology: A systematic review of the literature to assess the occurrence and clinical impact of noma and noma-like disease in HIV/AIDS patients was performed on PubMed, Virtual Health Library, Cochrane Library and Google Scholar using the keywords "HIV"[ All Fields] AND "Noma"[All Fields] in December 2016 (years includead for the search: 1985 to 2016). Results: Twenty-four published studies were identified that document the occurrence of noma or noma-like disease in a total of 133 HIV/AIDS children and adult patients in the last 22 years. Although HIV infection is not the principal risk factor for noma, in some regions may play a substantial role in its pathogenesis. The mortality rate for noma-like disease in HIV/AIDS patients was 54.3%, compared to the 15% mortality rate of treated noma patients without HIV/AIDS. Most of the cases have never been on antiretroviral therapy, and their HIV infection was discovered because of the noma-like disease. Conclusions: The syndemic interaction between HIV/AIDS and noma-like disease adversely impacts the severity of the disease and the mortality rate. Noma-like disease, although not yet considered a specific or frequent disease associated with HIV infection, should be considered as an opportunistic infection for AIDS.

Introduction: Outpatient parenteral antimicrobial therapy is a safe, effective, and convenient way of administering antimicrobials for a wide variety of infections. So far there are no reports on the efficacy of outpatient antimicrobial therapy in Mexico. Our objective was to determine the outcomes, safety, and cost of outpatient ertapenem therapy (OET) in our hospital. Patients and methods: A case series of 99 patients that received intravenous OET was conducted. The primary outcomes were clinical cure, relapse, and recurrence of infection. Results: Of the 99 patients who received OET the most common diagnosis was urinary tract infection in 56%. Extended-spectrum-β-lactamase-producing Enterobacteriaceae caused 67% of infections in our population. Ninety-seven percent of the patients were cured at the completion of OET. One patient presented relapse 12 days after the end of OET; two patients presented recurrence, one with skin and soft tissue infection and one with pyelonephritis at days 35 and 34, respectively, after the end of OET. Three patients were readmitted after OET, one with an episode of phlebitis, one with recurrence, and one with relapse. A case of non-Clostridium difficile-associated diarrhea was observed. The intravascular line complications observed during OET were phlebitis in two patients. Conclusion: In our hospital, the OET was found to be effective, safe, and cost-saving when compared to inpatient care.

Aspergillosis and mucormycosis are filamentous fungal infections occurring predominantly in immunocompromised patients. Fulminant process with rapid infiltration of the contiguous tissue is distinctive for both type of fungi. The rhinocerebral co-infection by Aspergillus and Mucorales is very rare and is usually associated in immunocompromised patients with a high mortality rate. This rare co-infection leads to difficulties in diagnosis, and therapeutic delays can result in a poor prognosis. Overall, the treatment of choice is surgical debridement and liposomal amphotericin B. This paper describes a combined aspergillosis and mucormycosis case in a diabetes mellitus type 2 patient with chronic ulcerations of the palatal and cheek. To our knowledge, this is the first report of an uncommon co-infection of Aspergillus fumigatus and Rhizopus arrhizus in a rhino-orbital presentation.