Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

OBJECTIVE: To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. METHODS: We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. RESULTS: Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. CONCLUSION: Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Incidence of Cytomegalovirus disease and viral replication kinetics in seropositive liver transplant recipients managed under preemptive therapy in a tertiary-care center in Mexico City: a retrospective cohort study.

BACKGROUND: In the absence of an adequate prevention strategy, up to 20% of CMV IgG+ liver transplant recipients (LTR) will develop CMV disease. Despite improved reporting in CMV-DNAemia, there is no consensus as to what the ideal CMV-DNAemia cutoff for a successful preemptive strategy is. Each transplant centre establishes their own threshold. We aimed to determine the effectiveness of our preventive strategy in CMV IgG+ LTR, and evaluate CMV replication kinetics. METHODS: In this retrospective study we determined the incidence of CMV disease in the first 6 months following transplantation in CMV seropositive LTR in a tertiary-care centre in Mexico. Secondary outcomes were determining the number of patients who required preemptive therapy (treatment cutoff ≥ 4000 UI/ml), adherence to the centre's prevention protocol and calculation of viral replication kinetics. RESULTS: One-hundred and twenty-four patients met inclusion criteria. Four patients (3.2%) developed CMV disease. Ninety-six (85%) had detectable DNAemia and 25 (22%) asymptomatic patients received preemptive therapy, none of them developed CMV disease. The highest viral loads were observed on the second posttransplant month. The number of viral load measurements decreased over time. Patients with DNAemia ≥ 4000 UI/ml had a faster viral load growth rate, shorter viral load duplication time, and higher basic reproductive number. Viral load growth rate and autoimmune hepatitis were associated with development of DNAemia ≥ 4000 UI/ml. CONCLUSION: Cytomegalovirus disease occurred in 3.2% of the study subjects. Preemptive therapy using a threshold of CMV ≥ 4000 UI/ml was effective in reducing the incidence of end-organ disease. The viral replication parameters described in this population highlight the importance of frequent monitoring, a challenging feat for transplant programs in low- and middle-income countries.

Immunology of Fungal Infections.

Complex processes mediate immunity to fungal infections. Responses vary depending on the organism, morphogenic state, and infection site. Innate immune effectors such as epithelia, phagocytes, and soluble molecules detect pathogens, kill fungi, release cytokines, and prime the adaptive response. Adaptive responses to mucocutaneous or invasive disease are markedly different but intersect at certain pathways (molecules required for IL-23 and IL-12 signaling). Many of these pathways have been elucidated from the study of inborn errors of immunity. This review explores the general aspects of antifungal immunity and delves into the mechanisms that mediate protection from frequently encountered fungi.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Bilateral Proximal Forearm Transplantation: Case Report at 7 Years.

BACKGROUND: Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT. CASE PRESENTATION: A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force. RESULTS: Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year. CONCLUSIONS: Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Treatment strategies and outcome of parvovirus b19 infection in kidney transplant recipients: a case series and literature review of 128 patients.

Abstract Background There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. Objective The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. Methods We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. Results In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. Conclusions In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Aspergillus infection of the larynx in a solid organ transplant recipient.

Primary laryngeal aspergillosis is a rare condition. Only a few cases have been reported in the past years. Most of them have been reported in healthy patients or with a mild immunocompromised state. We report a case of primary laryngeal aspergillosis in a solid organ transplant recipient (SOT), an infection not previously described in this population; we reviewed the published literature in all populations.

Association Between Frailty and HIV-Associated Neurodegenerative Disorders Among Older Adults Living with HIV.

The population of aging adults living with human immunodeficiency virus (HIV) is growing worldwide and evidence suggests that frailty occurs prematurely among them. In turn, frailty has been associated with cognitive decline. It is unknown, however, if people with both frailty and HIV infection have a higher risk of cognitive impairment compared with nonfrail HIV-infected persons. Therefore, the main objective of this study was to determine the association between the phenotype of frailty and HIV-associated neurocognitive disorders (HAND) among adults aged 50 years or older living with HIV/AIDS. A cross-sectional study was conducted on 206 adults living with HIV receiving care in a university-affiliated tertiary care hospital in Mexico City. Frailty was defined as per the Fried criteria. The presence of HAND was established according to the Antinori criteria: HIV-associated asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND), or cognitively nonimpaired. Multinomial logistic regression models were used to test the independent association between frailty and HAND adjusting for potential confounders. Mean age of participants was 60.5 ± 6.3 years and 84.9% were male. Prevalence of HAND and frailty phenotype was 66.0% and 2.9%, respectively. The unadjusted analysis showed that both prefrail and frail statuses were associated with MND but not with ANI. However, after adjustment, the association with MND remained significant only among prefrail participants and no longer for frail persons (risk ratio [RR] = 5.7, 95% confidence intervals [CI] 1.09-29.82; p = .039 and RR = 18.3, 95% CI 0.93-362.6; p = .056, respectively). Prefrailty is associated with symptomatic neurocognitive disorders in older adults living with HIV. The spectrum of the frailty phenotype in this already vulnerable population should serve as an indicator of concomitant cognitive decline.

Correlates of Prevalent Disability Among HIV-Infected Elderly Patients.

The growing elderly population of HIV-infected patients is leading to a significant epidemiological transition and HIV infection has been proposed as a premature and accelerated aging model rending the individual more susceptible to premature disability. However, the determinants of disability among this emergent population are still lacking. Therefore, the aim of this study is to determine the correlates of prevalent disability in adults ≥50 years with HIV infection. A cross-sectional study of 184 HIV-infected adults receiving ambulatory care in an HIV clinic of a tertiary care, university-affiliated hospital in Mexico City was conducted. Disability for instrumental (IADL) and basic activities of daily living (ADL) was established. Sociodemographic factors, clinical variables, current CD4(+) cell count, and HIV viral load (VL) were tested as potential determinants of disability. Multivariate logistic regression analyses were used to identify the correlates of both types of disability. The mean age was 59.3 years. All participants were receiving highly active antiretroviral therapy. Of participants 17.9% had disability for IADL and 26.1% for ADL. Multivariate logistic regression analyses indicated that being older; having a lower CD4(+) cell count, and having a detectable HIV VL were independently associated with both types of disability. In addition, educational level was also independently associated with ADL disability. Age, educational level, low CD4(+) cell count, and detectable HIV VL were independently associated with disability. Whether effective and timely antiretroviral therapy will reduce the risk of disability in HIV-infected elderly patients needs to be evaluated.

Surveillance of Oseltamivir-Resistant Influenza A(H1N1)pdm09 in Guanajuato State, Mexico from 2009 to 2012.

BACKGROUND: The influenza A(H1N1)pdm09 virus was first identified in Mexico in April 2009, subsequently spreading worldwide. Soon after the WHO declared a pandemic, a series of cases involving oseltamivir-resistant viruses were described, following concerns about the spread of strains resistant to neuraminidase inhibitors that could hamper control measures. To study the prevalence of oseltamivir-resistant influenza A(H1N1)pdm09, we implemented a surveillance program across the state of Guanajuato, Mexico. METHODS: We collected respiratory samples from patients with confirmed infection with influenza A(H1N1)pdm09 virus between 2009 and 2012 in rural and urban regions in Guanajuato, Mexico. Specimens were screened for the H275Y mutation by Sanger sequencing. RESULTS: A total of 1,192 laboratory confirmed influenza A(H1N1)pdm09-positive samples were processed between 2009 and 2012. Using two endpoint real-time polymerase chain reaction, 575 samples were sequenced. Two different clusters, I and II, were identified. The H275Y substitution was found in only one sample from cluster I. CONCLUSIONS: The prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 2009 viruses during the pandemic period and following years was very low in our State.

Rapid detection of ESBL-producing gram-negative bacteria isolated from blood: a reasonable and reliable tool for middle and low resource countries.

INTRODUCTION: Delay in appropriate treatment in patients with bacteraemia can increase morbidity, mortality, and health expenditures. We compared the Rapid Direct Test (RDT) designed to detect ESBL-producing gram-negative bacteria (GNB) directly from positive blood cultures bottles, with two conventional ESBL detection tests: Screening and Confirmatory Disk Diffusion Assay (SC-DDA) and an MIC Screening and ESBL E-test (MIC/ET). MATERIAL AND METHODS: We screened all blood cultures in a tertiary care facility from August to December 2005. We only included one positive bottle per patient in which GNB were observed. RDT: Blood from each bottle was inoculated on Mueller-Hinton agar. Ceftazidime and cefotaxime disks with and without clavulanic acid were added and incubated at 35 degrees C +/- 2 degrees C for 24 h. Results were interpreted according to CLSI recommendations for the SC-DDA and MIC/ET. All methods were performed simultaneously. Time for reporting as an ESBL-producer and cost of the tests were recorded. RESULTS: We isolated 124 GNB in 114 episodes of bacteraemia, 10 of them (8.8%) polymicrobial; 79 (63.7%) of the GNB were enteric bacteria, 44 (35.5%) glucose non-fermenter GNB and one Haemophilus influenzae. The most common microorganism was Escherichia coli in 56 episodes (45.2%), followed by Pseudomonas aeruginosa in 24 (19.3%), and Klebsiella pneumoniae in 13 (10.5%). Of the 114 episodes, 41 (36%) had at least one GNB resistant to 3rd generation cephalosporins, and 25 (21.9%) were caused by an ESBL-producing GNB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the RDT were 96%, 98.9%, 96% and 98.9%, respectively. Agreement by kappa index between RDT and SC-DDA was 0.95 and between the RDT and MIC/ET was 0.92. The RDT detected 24/25 ESBL-producing bacteria. The mean time to detect an isolate as an ESBL producer after a positive blood culture bottle signal was 1.02 +/- 0.19 days when using the RDT, and 3.40 +/- 0.59 days when using any other method. The difference in reporting time was 2.38 +/- 0.63 days (p < 0.0001). Our estimated cost per test was $1.54 for RDT, $2.32 for screening/ confirmatory SC-DDA, and $49.65 for MIC screening and MIC/ET. Conclusions. The RDT is a rapid, reliable and easy analysis to perform, as well as cost-effective.

Early loss of measles antibodies after MMR vaccine among HIV-infected adults receiving HAART.

OBJECTIVE: The objective of the study was to evaluate the immune response to measles vaccine of HIV-infected adults in comparison to HIV non-infected adults. DESIGN: We conducted a cross-sectional study to identify adults lacking measles antibodies. 26 HIV-infected patients and 22 controls found to be measles seronegative in the cross-sectional study, received the MMR vaccine. We prospectively followed patients and measured measles antibodies, and cellular proliferative responses against measles antigens. We registered all adverse events at baseline, 3 and 12 months after vaccination. METHODS: We determined measles antibodies by ELISA and cellular proliferative response in PBMC's at baseline, and repeated measurements at 3 and 12 months after vaccination. RESULTS: The humoral immune response to the vaccine between HIV-infected adults and the HIV-uninfected group was not statistically different at 3 months (81% vs. 86% respectively). One year after vaccination, a higher proportion of HIV-infected adults had lost measles antibodies in contrast to controls. The cellular response was not statistically different between the groups at baseline, 3 and 12 months after immunization despite the waning of antibodies at 12 months. No severe adverse events were observed. Most patients were receiving HAART and had a mean CD4+ cell count of 496 cells/mL. CONCLUSIONS: The initial humoral immune response to measles vaccine was not different between HIV-infected adults and HIV-uninfected adults. However, HIV-infected adults have a rapid decline of measles antibodies despite their high CD4+ cell count and sustained cellular proliferative response.

Infecciones en pacientes sometidos a trasplante de órgano sólido / Infections in solid organ transplant recipients

The main problems in solid organ transplant recipients are rejection and infections. The new immunosuppressive regimens have lowered the risk of rejection, however, infections continue to be one of the most important determinants for morbidity and mortality in these patients. The survival of the transplanted organ is also impacted by the different infectious diseases that occur in the post-transplant period. These infections are of viral, bacterial, fungal and parasitic origin, and their presentation occurs characteristically within well defined risk periods after the transplant. The clinical presentation is commonly atypical; therefore for optimal management, it is necessary to have a through knowledge of the epidemiology and clinical manifestations of these problems, but most importantly, the experience of the clinician in the clinical approach and early detection will result in better outcomes. We review recent information regarding the infectious diseases that affect solid organ recipients according to the type of transplant, the post-transplant, risk factors before the transplant and the type of immunosuppressive therapy used, which are the main determinants for these complications and their prognosis.

Los problemas principales en el paciente sometido a trasplante de órgano sólido (TOS) son el rechazo del órgano y las infecciones. Los nuevos esquemas inmunosupresores han disminuido el riesgo de rechazo, sin embargo, las infecciones siguen siendo uno de los determinantes más importantes de morbilidad y mortalidad en estos pacientes. La sobrevida del órgano trasplantado es impactada también por los diversos procesos infecciosos que ocurren en el periodo postrasplante. Las infecciones que afectan a estos pacientes son de origen viral, bacteriano, fúngico y parasitario y su presentación ocurre característicamente dentro de periodos bien definidos de riesgo posterior al trasplante. La presentación clínica frecuentemente es atípica, por lo que para el manejo óptimo es necesario conocer la epidemiología y las manifestaciones clínicas de estos problemas, pero sobre todo la experiencia del clínico en el abordaje y en la detección temprana resulta en un mejor desenlace. En este artículo se revisa la información reciente sobre las enfermedades infecciosas que afectan a pacientes sometidos a TOS de acuerdo con el tipo de trasplante, al periodo postrasplante, a los factores de riesgo previo al trasplante y al tipo de terapia inmunosupresora utilizada, los cuales son los principales determinantes de estas complicaciones y de su pronóstico.

[Infections in solid organ transplant recipients]. / Infecciones en pacientes sometidos a trasplante de organo sólido.

The main problems in solid organ transplant recipients are rejection and infections. The new immunosuppressive regimens have lowered the risk of rejection, however, infections continue to be one of the most important determinants for morbidity and mortality in these patients. The survival of the transplanted organ is also impacted by the different infectious diseases that occur in the post-transplant period. These infections are of viral, bacterial, fungal and parasitic origin, and their presentation occurs characteristically within well defined risk periods after the transplant. The clinical presentation is commonly atypical; therefore for optimal management, it is necessary to have a through knowledge of the epidemiology and clinical manifestations of these problems, but most importantly, the experience of the clinician in the clinical approach and early detection will result in better outcomes. We review recent information regarding the infectious diseases that affect solid organ recipients according to the type of transplant, the post-transplant, risk factors before the transplant and the type of immunosuppressive therapy used, which are the main determinants for these complications and their prognosis.