Characteristics and outcomes of people living with HIV hospitalised at tertiary healthcare institutions during the COVID-19 pandemic in Mexico City.

BACKGROUND: While existing research on people living with HIV (PWH) during the COVID-19 pandemic primarily focused on their clinical outcomes, a critical gap remains in understanding the implications of COVID-19 delivery of in-hospital care services to PWH. Our study aimed to describe the characteristics and outcomes of PWH hospitalised during 2020 in Mexico City, comparing patients admitted due to COVID-19 vs. patients admitted due to other causes. METHODS: All PWH hospitalised for ≥ 24 h at four institutions in Mexico City from January 1st to December 31st, 2020 were included. Patients were classified into two groups according to the leading cause of their first hospitalisation: COVID-19 or non-COVID-19. Characteristics among groups were compared using chi-square and Kruskal tests. A Cox model was used to describe the risk of death after hospitalisation and the characteristics associated with this outcome. Mortality and hospitalisation events were compared to data from 2019. RESULTS: Overall, we included 238 PWH hospitalised in 2020. Among them, 42 (18%) were hospitalised due to COVID-19 and 196 (82%) due to non-COVID-19 causes, mainly AIDS-defining events (ADE). PWH hospitalised due to COVID-19 had higher CD4 + cell counts (380 cells/mm3 [IQR: 184-580] vs. 97 cells/mm3 [IQR: 34-272], p < 0.01) and a higher proportion of virologic suppression (VS) compared to those hospitalised due to non-COVID-19 causes (92% vs. 55%, p < 0.01). The adjusted hazard ratio (aHR) for AIDS was 3.1 (95%CI: 1.3-7.2). COVID-19 was not associated with death (aHR 0.9 [95%CI: 0.3-2.9]). Compared to 2019, mortality was significantly higher in 2020 (19% vs. 9%, p < 0.01), while hospitalisations decreased by 57%. CONCLUSIONS: PWH with COVID-19 had higher VS and CD4 + cell counts and lower mortality compared to those hospitalised due to non-COVID-19-related causes, who more often were recently diagnosed with HIV and had ADEs. Most hospitalisations and deaths in 2020 in PWH were related to advanced HIV disease. The increased mortality and decreased hospitalisations of PWH during 2020 evidence the impact of the interruption of health services delivery for PWH with advanced disease due to the pandemic. Our findings highlight the challenges faced by PWH during 2020 in a country where advanced HIV remains a concern.

Bacterial incidence and drug resistance from pathogens recovered from blood, cerebrospinal and pleural fluids in 2019-2020. Results of the Invifar network.

Background: Antimicrobial resistance is a global concern. Analysis of sterile fluids is essential because microorganisms are defined as significant in most cases. Blood, cerebrospinal, and pleural fluids are frequently received in the microbiology lab because they are associated with considerable rates of morbi-mortality. Knowledge of epidemiology in these samples is needed to choose proper empirical treatments due to the importance of reducing selection pressure. Methods: We used retrospective laboratory data of blood, CSF, and pleural fluid collected from patients in Mexico between 2019 and 2020. Each laboratory identified the strains and tested susceptibility using its routine methods. For Streptococcus pneumoniae, a comparative analysis was performed with data from the broth microdilution method. Results: Forty-five centers participated in the study, with 30,746 clinical isolates from blood, 2,429 from pleural fluid, and 2,275 from CSF. For blood and CSF, Staphylococcus epidermidis was the most frequent. For blood, among gram negatives, the most frequent was Escherichia coli. Among Enterobacterales, 9.8% of K. pneumoniae were carbapenem-resistant. For S. pneumoniae, similar resistance percentages were observed for levofloxacin, cefotaxime, and vancomycin. For CSF, the most frequent gram-negative was E. coli. In Acinetobacter baumannii, carbapenem resistance was 71.4%. The most frequent species detected for pleural fluid was E. coli; in A. baumannii, carbapenem resistance was 96.3%. Conclusion: Gram-negative bacteria, with E. coli most prevalent, are frequently recovered from CSF, blood, and pleural fluid. In S. pneumoniae, the routine, conventional methods showed good agreement in detecting resistance percentages for erythromycin, levofloxacin, and vancomycin.

Increment Antimicrobial Resistance During the COVID-19 Pandemic: Results from the Invifar Network.

Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

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.

General hospital outbreak of invasive candidiasis due to azole-resistant Candida parapsilosis associated with an Erg11 Y132F mutation.

An increasing number of outbreaks due to resistant non-albicans Candida species have been reported worldwide. Between 2014 and 2016, Candida isolates causing invasive candidiasis were recovered in a Mexican hospital. Isolates were identified to species level and antifungal susceptibility was determined. In the time period studied, 74 invasive candidiasis cases were identified, with 38% (28/74) caused by Candida parapsilosis, out of which 54% (15/28) were fluconazole resistant. The ERG11 gene was sequenced for 12 recoverable fluconazole-resistant C. parapsilosis isolates and SNPs identified. The 12 isolates had one common silent point mutation in ERG11 (T591C) and seven isolates had an additional (A395T) mutation, which corresponded to Y132F. Four of the isolates carrying this mutation were closely related within the same cluster by microsatellite typing. This is the first report of an invasive candidiasis outbreak in Mexico due to azole-resistant C. parapsilosis associated with the Y132F substitution.

Species identification of Enterococcus spp: Whole genome sequencing compared to three biochemical test-based systems and two Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) systems.

AIM: Here, we evaluated the performance of two commercial MALDI-TOF MS systems and three biochemical-based systems and compared them to WGS as the gold standard for identifying isolates of vancomycin-resistant enterococci (VRE). METHODS: A total of 87 VRE clinical isolates were included. The mass spectrometers were the Microflex system with Biotyper software 3.1 and the Vitek MS system. The biochemical-based systems included the Vitek 2, Phoenix, and MicroScan WalkAway systems. WGS was performed on an Illumina MiSeq instrument using the MiSeq v3 reagent kit. Vancomycin resistance was determined according to CLSI criteria. RESULTS: Among the 87 VRE, 71 and 16 were identified as Enterococcus faecium and Enterococcus faecalis by WGS. All 71 E faecium were correctly identified by both mass spectrometers, as well as the Vitek 2 and Phoenix instruments. However, only 51 E faecium isolates were correctly identified by the MicroScan system. The most frequent misidentification was Enterococcus casseliflavus (n = 20). For vancomycin-resistant E faecium, the Microflex Biotyper system had the highest sensitivity (85.54%), and all instruments (except for the Microscan) had a 100% specificity and PPV. Up to 87% of E faecalis isolates were misidentified by VITEK MS and VITEK2, 81% by Microscan and Phoenix, and 75% by Bruker biotyper. CONCLUSION: As the coverage of type strain-genome sequence database continues to grow and the cost of DNA sequencing continues to decrease, genome-based identification can be a useful tool for diagnostic laboratories, with its superior accuracy even over MALDI-TOF and database-driven operations.

Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection.

Aim: In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI). Methods: We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing. Results: We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor's pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041). Conclusion: Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.

Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Increasing rates of Clostridium difficile infection in Mexican hospitals

Abstract Introduction The epidemiology of Clostridium difficile infection (CDI) has changed in the last two decades. There is a lack of information regarding incidence and severity of CDI, especially in the developing world. Methods This was a retrospective and observational study from four hospitals of three Mexican cities. Patients were diagnosed with CDI when presented with loose stools and had at least one of the following tests positive: toxins assay, real-time PCR, or an endoscopic image compatible with pseudomembranous colitis. CDI was classified according to international guidelines. Demographic and clinical data as well as information regarding total hospital admissions, total length-of-hospital stay, and other variables related to hospitalization were gathered from the epidemiology and administration departments of each hospital. Results A total of 2050 hospital beds were analyzed with 288,171 patients hospitalized accumulating 1,576,446 days of hospitalization during the study period. The average rate of CDI per 1000 hospital-days was lower than the rates reported in the US and Europe, although in 2015 CDI rates were almost persistently above the mean rate for the study period. More than half of PCR positive patients were ribotype 027. Conclusion Hospital rates of CDI are increasing in Mexican hospitals with a predominance of infections caused by ribotype 027.

Higher In vitro Proliferation Rate of Rhizopus oryzae in Blood of Diabetic Individuals in Chronic Glycaemic Control Compared with Non-diabetic Individuals.

Metabolic control improves outcomes associated with mucormycosis. The aim of this study was to compare the in vitro proliferation of Rhizopus oryzae in blood of individuals with and without diabetes at different glycaemic levels. Ninety-five individuals were included. Blood samples from each participant were incubated with sporangiospores of R. oryzae. The germination, filamentation and growth of R. oryzae were compared at different time points. Four groups were defined, one without (group A, n = 30) and three with diabetes: group B (HbA1c ≤7%, N = 24), group C (HbA1c 7.1-9%, N = 20) and group D (HbA1c > 9%, N = 21). The percentage of germinated sporangiospores was higher in the group A after 6 h (group A 56% ± 3, group B 35% ± 4, group C 48% ± 4, group D 46% ± 1.4, p = 0.01), 12 h (group A 54% ± 1.4, group B 19% ± 4, group C 16% ± 1, group D 9.5% ± 5, p < 0.001) and 24 h (group A 29% ± 1, group B 12% ± 4, group C 13.5% ± 3.5, group D 12% ± 1, p < 0.01). The filamentation was higher in groups with diabetes. Group B showed higher filamentation grade than group A at 6 h (0.4 ± 0.04 vs 1 ± 0.09, p < 0.001) and 24 h (1.6 ± 0.05 vs 2.1 ± 0.1, p = 0.05). In conclusion, R. oryzae proliferation was higher among diabetic individuals, including good glycaemic control, than among non-diabetic individuals.

Sociodemographic differences among HIV-positive and HIV-negative recently pregnant women in Mexico City: A case-control study.

National HIV preventive programs in Mexico focus on high-risk groups that do not consider women, apart from prenatal screening. Nonetheless, the epidemic in women is growing, and there is a need to better understand sociodemographic factors in women living with HIV (WLH). We performed a case-control study in Mexico City, including HIV+ and HIV- women with a recent pregnancy to compare their sociodemographic characteristics and describe the circumstances of diagnosis in HIV+ women, as well as prenatal screening frequency in both groups. Fifty cases and 102 controls were interviewed. HIV+ women were more frequently the only economic support of the family (20% vs 0%, P < .0001). Thirty-eight percent of cases had their first pregnancy at ≤18 years, versus 16% of controls (odds ratio 2.47, 95% confidence interval 1.07-5.72, P = .03); 16% of cases had lived in the street; 6% reported transactional sex, versus none of the controls (P < .0001). In the multivariate analysis, there was strong evidence of an association between HIV infection and age at the time of the interview, history of sexually transmitted diseases, substance abuse, history of violence, and civil status. Only 6% of controls were tested for HIV during prenatal follow-up. WLH in this study faced important social vulnerability. Targeting women living in these social contexts might increase early diagnosis and could tailor HIV prevention strategies. Prenatal coverage needs to be improved and should represent a national priority.

Increasing rates of Clostridium difficile infection in Mexican hospitals.

INTRODUCTION: The epidemiology of Clostridium difficile infection (CDI) has changed in the last two decades. There is a lack of information regarding incidence and severity of CDI, especially in the developing world. METHODS: This was a retrospective and observational study from four hospitals of three Mexican cities. Patients were diagnosed with CDI when presented with loose stools and had at least one of the following tests positive: toxins assay, real-time PCR, or an endoscopic image compatible with pseudomembranous colitis. CDI was classified according to international guidelines. Demographic and clinical data as well as information regarding total hospital admissions, total length-of-hospital stay, and other variables related to hospitalization were gathered from the epidemiology and administration departments of each hospital. RESULTS: A total of 2050 hospital beds were analyzed with 288,171 patients hospitalized accumulating 1,576,446 days of hospitalization during the study period. The average rate of CDI per 1000 hospital-days was lower than the rates reported in the US and Europe, although in 2015 CDI rates were almost persistently above the mean rate for the study period. More than half of PCR positive patients were ribotype 027. CONCLUSION: Hospital rates of CDI are increasing in Mexican hospitals with a predominance of infections caused by ribotype 027.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel µl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.

Plasma cytokine levels and cytokine gene polymorphisms in Mexican patients during the influenza pandemic A(H1N1)pdm09.

BACKGROUND: In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production. OBJECTIVES: The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic. STUDY DESIGN: Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFß)1 and TGFß2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed. RESULTS: Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)]. CONCLUSIONS: This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.

New tetratrichomonas species in two patients with pleural empyema.

Two unusual occurrences of pleural trichomonosis due to a new Tetratrichomonas species previously reported but not named were confirmed. In one patient, Trichomonas tenax and a Tetratrichomonas species were also detected in the oral cavity by molecular methods. We suggest that this new Tetratrichomonas species be named Tetratrichomonas empyemagena.