Impact of the Vaccination Against COVID-19 on Frontline Health Workers.

INTRODUCTION: Brazil has been facing the pandemic of COVID-19 since march 2020. More than 540,000 people have died from this disease in the country. Some estimates indicate that the population exposed to SARS-CoV-2 represents 1 to 20%. However, these data are questionable due to the number of asymptomatic and untested individuals. As a result, vaccination for COVID- 19 has become the main means of achieving herd immunity. OBJECTIVES: To demonstrate, through local sampling, that broad and rapid vaccination may decrease the rate of COVID-19 detection in individuals potentially exposed to the SARS-CoV-2 virus. METHODS: A total of 1,128 individuals were studied, including students and health professionals from Centro Universitário FMABC, who received the two doses of the vaccine for COVID-19 (Oxford/Astrazeneca ® and CoronaVac®). RESULTS: In the studied period, there was a 41% reduction in the demand for RT-PCR tests after vaccination. And a 78.3% reduction in positive results after vaccination started. CONCLUSION: The results of this study showed that even vaccinating a population with higher exposure to the risk of contamination significantly reduced test positivity and the demand to perform these tests. This emphasizes that vaccination is the best strategy to achieve herd immunity and reduce the spread of the disease.

Ganglionar tuberculosis infection evolving to hemophagocytic lymphohistiocytosis after anti-programmed cell death 1 treatment for high-risk melanoma: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare, potentially fatal syndrome of immune hyperactivation. Here we describe a ganglionar tuberculosis evolving to hemophagocytic lymphohistiocytosis following adjuvant immunotherapy in a melanoma patient. CASE PRESENTATION: A 76-year-old Caucasian male with melanoma started with fever, diffuse petechiae, splenomegaly, anemia, thrombocytopenia, hypofibrinogenemia, and hyperferritinemia 2 months following completion of adjuvant treatment with nivolumab. Positron emission tomography scan showed significant hypermetabolism in cervical, supraclavicular, mediastinal, and abdominal lymph nodes. Bone marrow aspiration demonstrated no alterations, except for a hypercellular pattern. Dexamethasone and intravenous immunoglobulin were started owing to suspicion of hemophagocytic lymphohistiocytosis. Core biopsy of the infracarinal lymph node revealed a chronic granulomatous inflammation and caseous necrosis, with positivity for Mycobacterium tuberculosis by polymerase chain reaction, and treatment for ganglionar tuberculosis was started. CONCLUSION: This case highlights the challenges involving programmed cell death 1 blockade in high-risk melanoma, in which infections, lymphoproliferative disorders, and sarcoidosis can mimic disease progression and trigger immune-related adverse events.

Osteonecrosis of the femoral head in people living with HIV: anatomopathological description and p24 antigen test.

OBJECTIVE: To examine the presence of HIV in bone tissue of people living with HIV (PLWHIV) with osteonecrosis of femoral head and describe clinical and anatomopathological findings. DESIGN: This is a case series which included 44 PLWHIV with osteonecrosis of femoral head who underwent total hip arthroplasty. METHODS: Clinical data were obtained through analysis of the patients' medical records. Bone tissue obtained during total hip arthroplasty was retrieved and sent for conventional and immunohistochemical analysis. Monoclonal antibodies were used to mark the p24 (HIV), CD31 (vascular endothelial cells), CD68 (macrophages), and D240 (cells of the lymphatic endothelium) antigens. RESULTS: Dyslipidemia was found in 48% of the patients and lipodystrophy in 31%. Histological analysis showed similar characteristics for the entire sample. Degeneration of joint cartilage was visualized with the presence of fissures and fibrillations, as well as subchondral sclerosis and necrosis of the subchondral cancellous bone tissue. Lymphoplasmocytic inflammatory reaction was observed, with the presence of macrophages containing a foamy, vacuolated cytoplasm, as well as the presence of ceroid pigment and occasional granulation tissue. The reaction with the monoclonal anti-p24 antibody was negative in the samples from all 44 PLWHIV undergoing hip arthroplasty. Reactions with the anti-CD31 and anti-D240 antibodies were negative. Staining with CD68 antibody confirmed that the cells visualized with foamy, vacuolated cytoplasm were macrophages. CONCLUSION: p24 HIV antigen was not detected in the bone tissue of PLWHIV and osteonecrosis. The most frequent anatomopathological findings were extensive necrosis of bone tissue, large vacuoles filled with fat cells, inflammatory lymphoplasmocytic reaction with macrophages containing vacuolated cytoplasm, and the presence of ceroid pigment.

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6-20.7) and 32.3 (95% CI 27.3-38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58-5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.

Toxoplasma gondii Myocarditis after Adult Heart Transplantation: Successful Prophylaxis with Pyrimethamine.

Toxoplasma gondii primary infection/reactivation after solid organ transplantation is a serious complication, due to the high mortality rate following disseminated disease. We performed a retrospective study of all cases of T. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our Institution from May 1968 to January 2011. Six patients (1.3%) developed T. gondii infection/reactivation in the post-operative period. All infections/reactivations occurred before 1996, when no standardized toxoplasmosis prophylactic regimen or co-trimoxazole prophylaxis was used. Starting with the 112th heart transplant, oral pyrimethamine 75 mg/day was used for seronegative transplant recipients whose donors were seropositive or unknown. Two patients (33.3%) presented with disseminated toxoplasmosis infection, and all patients (100%) had myocarditis. Five patients (83.3%) were seronegative before transplant and one patient did not have pre-transplant serology available. Median time for infection onset was 131 days following transplantation. Three patients (50%) died due to toxoplasmosis infection. After 1996, we did not observe any additional cases of T. gondii infection/reactivation. In conclusion, toxoplasmosis in heart allographs was more frequent among seronegative heart recipients, and oral pyrimethamine was highly effective for the prevention of T. gondii infection in this population.

Hepatitis delta in HIV/HBV co-infected patients in Brazil: is it important?

OBJECTIVES: This study was carried out to evaluate the prevalence of hepatitis delta virus (HDV) among human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected patients from São Paulo, in the Southeast Region of Brazil. METHODS: A total of 3259 HIV patients with serological markers for HBV were initially enrolled in the study. Among these patients, 154 (4.7%) were hepatitis B surface antigen (HBsAg)-reactive. Serum samples were obtained from 86 HBsAg-positive patients and were submitted to anti-HDV serological assay. RESULTS: One (1.2%) HIV/HBV patient was found to be anti-HDV-positive, and the HDV infection was confirmed by PCR. Phylogenetic analysis showed that this HDV sequence grouped with other HDV genotype 1 sequences from Mediterranean European countries, suggesting that this virus has a common ancestor with HDV from that region. This patient was probably infected by sexual transmission, as he reported unprotected sexual intercourse with multiple partners over the course of many years but denied intravenous drug use or any travel to the Brazilian Amazon, an area known to have a high HDV prevalence. CONCLUSIONS: HDV infection is infrequent in the Southeast Region of Brazil, however there have been a few cases in this region. HIV/HBV patients are at potential risk for HDV infection, therefore investigations for the presence of HDV infection must be carried out in these patients.

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil.

BACKGROUND: HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort. METHODS: A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression. RESULTS: A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48.9%) patients were HBeAg positive and 44 (51.1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0.047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0.001) and ALT levels above normality (p = 0.038). CONCLUSION: Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.

Subacromial bursitis related to HIV infection: case report.

OBJECTIVE: Describe a subacromial bursitis at the right shoulder of a 45-year-old male subject. The patient has been living with HIV/AIDS for 22 years. METHODS: The ultrasonography and the MRI revealed the presence of a pronounced subacromial effusion, with an inflammatory reaction of adjacent tissues. The tumoration was handled firstly with a needle-puncture aspiration, with a thick liquid outflow, followed by an open drainage. Histopathological evaluation showed no evidence of any AIDS defining disease. There was complete remission of the infection after five months thereafter the symptoms had started. CONCLUSION: After reviewing the scarce literature in the area, no reports of subacromial bursitis in HIV/AIDS patients were found. The authors point out that, although rare, this disease should be considered as differential diagnosis of shoulder diseases in HIV-infected subjects.

Malignant and tuberculous pleural effusions: immunophenotypic cellular characterization.

INTRODUCTION AND OBJECTIVES: Tuberculosis and cancer are the main causes of pleural effusion. Pleural involvement is associated with migration of immune cells to the pleural cavity. We sought to characterize the immunophenotype of leukocytes in the pleural effusion and peripheral blood of patients with tuberculosis or malignancy. METHODS: Thirty patients with tuberculosis (14) or malignancy (16) were studied. A control group included 20 healthy blood donors. RESULTS: Malignant phycoerythrin pleural effusions showed higher percentages of CD3, CD4, CD3CD45RO, and CD20CD25 lymphocytes and lower percentages of CD3CD25 and CD20HLA-DR when compared to PB lymphocytes. Compared to PB, tuberculous effusions had a higher percentage of lymphocytes that co-expressed CD3, CD4, CD3CD45RO, CD3TCRalphabeta, CD3CD28, and CD20 and a lower percentage of CD14, CD8 and CD3TCRgammadelta-positive lymphocytes. Malignant effusions presented higher expression of CD14 whereas tuberculous effusions had higher expression of CD3 and CD3CD95L. Peripheral blood cells from tuberculosis patients showed higher expression of CD14, CD20CD25 and CD3CD95L. Compared with the control cells, tuberculosis and cancer peripheral blood cells presented a lower percentage of CD3CD4 and CD3CD28-positive cells as well as a higher percentage of CD3CD8, CD3CD25 and CD3CD80-positive cells. CONCLUSIONS: Tuberculous and malignant peripheral blood is enriched with lymphocytes with a helper/inducer T cell phenotype, which are mainly of memory cells. CD14-positive cells were more frequently found in malignant effusions, while CD3-positive cells expressing Fas ligand were more frequently found in tuberculous effusions.

Malignant and tuberculous pleural effusions: immunophenotypic cellular characterization

INTRODUCTION AND OBJECTIVES: Tuberculosis and cancer are the main causes of pleural effusion. Pleural involvement is associated with migration of immune cells to the pleural cavity. We sought to characterize the immunophenotype of leukocytes in the pleural effusion and peripheral blood of patients with tuberculosis or malignancy. METHODS: Thirty patients with tuberculosis (14) or malignancy (16) were studied. A control group included 20 healthy blood donors. RESULTS: Malignant phycoerythrin pleural effusions showed higher percentages of CD3, CD4, CD3CD45RO, and CD20CD25 lymphocytes and lower percentages of CD3CD25 and CD20HLA-DR when compared to PB lymphocytes. Compared to PB, tuberculous effusions had a higher percentage of lymphocytes that co-expressed CD3, CD4, CD3CD45RO, CD3TCRáâ, CD3CD28, and CD20 and a lower percentage of CD14, CD8 and CD3TCRãä-positive lymphocytes. Malignant effusions presented higher expression of CD14 whereas tuberculous effusions had higher expression of CD3 and CD3CD95L. Peripheral blood cells from tuberculosis patients showed higher expression of CD14, CD20CD25 and CD3CD95L. Compared with the control cells, tuberculosis and cancer peripheral blood cells presented a lower percentage of CD3CD4 and CD3CD28-positive cells as well as a higher percentage of CD3CD8, CD3CD25 and CD3CD80-positive cells. CONCLUSIONS: Tuberculous and malignant peripheral blood is enriched with lymphocytes with a helper/inducer T cell phenotype, which are mainly of memory cells. CD14-positive cells were more frequently found in malignant effusions, while CD3-positive cells expressing Fas ligand were more frequently found in tuberculous effusions.

Are adverse events of nevirapine and efavirenz related to plasma concentrations?

OBJECTIVE: The relationships between adverse events (AEs) and plasma concentrations of nevirapine (NVP) and efavirenz (EFV) were investigated as part of the large, international, randomized 2NN study. METHODS: Treatment-naive, HIV-1-infected patients received NVP (once or twice daily), EFV or their combination, each in combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Concentrations of NVP and EFV were quantitatively assessed by a validated HPLC assay. Individual Bayesian estimates of the area under the plasma concentration-time curve over 24 h (AUC24h), and minimum and maximum plasma concentrations (Cmin and Cmax) as measures for drug exposure of NVP and EFV, were generated using a previously developed population pharmacokinetic model. Pharmacokinetic parameters were compared for patients with and without central nervous system (CNS) and psychiatric AEs, hepatic events, liver enzyme elevations (LEEs) and rash. Furthermore, it was investigated whether a clear cut-off for a pharmacokinetic parameter could be identified above which the incidence of AEs was clearly increased. AEs were also related to demographic parameters and baseline characteristics. RESULTS: In total, from 1077 patients, NVP (3024 samples) and EFV (1694 samples) plasma concentrations and AE data (825 observations) were available. For all patients Cmin, Cmax and AUC24h were determined. When corrected for known covariates of gender, CD4 cell count at baseline, region, hepatitis coinfection and possible interactions between these factors, no significant associations between AEs and any tested exposure parameter of NVP was observed. Also, no target Cmin value, above which patients were at increased risk for AEs, could be established. On the other hand, geographical region, hepatitis coinfection, CD4 cell count and gender were found to be significantly related with the incidence of CNS and psychiatric AEs, hepatic events, LEEs and rash during the treatment with NVP. The occurrence of elevated liver enzymes during the first 6 weeks in the EFV-containing arm was significantly (P = 0.036) correlated to the exposure of EFV (Cmin). Only hepatitis coinfection impacted on LEEs during the first 6 weeks of treatment. With an EFV Cmin above 2.18 mg/l during the induction phase, patients were 4.4 (range 1.3-15.5) times more at risk for elevated liver enzymes. No other correlations between AEs and EFV pharmacokinetics or patient characteristics could be identified. CONCLUSIONS: Pharmacokinetic parameters of NVP did not have a relationship to AEs in the 2NN trial when corrected for known covariates. The value of periodical drug monitoring of NVP as a way to prevent toxicity is therefore limited. Treating physicians should instead focus on factors that are more predictive of AEs (gender, CD4 count and hepatitis coinfection). High EFV Cmin levels resulted in elevated liver enzyme values during the first 6 weeks of treatment. Regular measurement of EFV levels and liver enzymes at the start of therapy may therefore be advised.

Human papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women.

HIV-infected women from S o Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD(4)(+) cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%). Twenty (7.5%) women were infected by one or more low-risk viruses, 89 (33%) by one or more high-risk viruses, and 64 (24%) harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD(4)/microL <100) were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

Human papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

HIV-infected women from S o Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD(4)(+) cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5). Twenty (7.5) women were infected by one or more low-risk viruses, 89 (33) by one or more high-risk viruses, and 64 (24) harbored at least one HPV type from each risk group. Abnormal smears were observed in 19 of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD(4)/microL <100) were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

Detection of Mycobacteria in the bloodstream of patients with Acquired Immunodeficiency Syndrome in a University Hospital in Brazil

This study was done to determine the occurrence of mycobacteria in the bloodstreams of patients with fever and advanced AIDS in a Brazilian hospital. We also verified the capability of an automated method for recovering these bacteria. During a period of 19 months, 254 patients with AIDS were evaluated. Blood cultures were generally submitted in pairs and drawn separately. Blood cultures were processed by the BACTEC 460TB System (Becton Dickinson Microbiology Systems, Sparks, MD). Of the 530 vials submitted, 77 (14.5 percent) from 41 (16 percent) patients were positive. Mycobacterium avium complex was recovered from 45 (58.4 percent) of the 77 positive vials, corresponding to 22 (53.6 percent) patients with positive blood cultures. The average time to detect Mycobacterium avium complex was 15 days. Mycobacterium tuberculosis was recovered from 26 (33.8 percent) of the 77 positive vials, corresponding to 15 (36.6 percent) patients with positive blood cultures, with an average detection time of 24 days. Other species of mycobacteria were recovered from 6 (7.8 percent) of the 77 vials, corresponding to 4 (9.8 percent) patients. M. avium complex was fairly prevalent (8.7 percent) in severely ill patients with AIDS in our hospital. M. tuberculosis was also an important (6.0 percent) agent of systemic bacterial infections in these patients. The rapid diagnosis of mycobacteremia was possible with the implementation of this automated technology.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive hiv-infected individuals with CD4 cell counts between 50 and 250/mm3

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (<0.0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70 percent and 61 percent, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated

Abscesso cerebelar por nocardia: relato de caso / Cerebellar abscess by Nocardia: a case report

A nocardiose do sistema nervoso central tem alcançado importante destaque no diagnóstico diferencial de patologias tumorais nos últimos anos pelo aumento da incidência de pacientes imunodeficiêntes (pacientes submetidos a quimioterapia, transplante de órgäos ou com a síndrome de imunodeficiência adquirida - SIDA. Os autores descrevem o caso de um paciente com SIDA que desenvolveu nocardiose cerebelar na sua forma tumoral. O paciente foi submetido a craniectomia de fossa posterior para diagnóstico e tratamento. Os achados de neuroimagem e patológicos bem como a conduta cirúrgica säo discutidos com base em revisäo da literatura