Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of ...community-acquired bacterial meningitis.
The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction.
Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test.
From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible.
Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.
Background and purpose
This case illustrates for the first time the clinical and radiological evolution of SARS‐CoV‐2 meningo‐encephalitis.
Methods
A case of a SARS‐CoV‐2 meningo‐encephalitis is ...reported.
Results
A 65‐year‐old man with COVID‐19 presenting with meningo‐encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. Examination disclosed a convergence strabismus and ataxia. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, oligoclonal bands and increased interleukin 6 level. SARS‐CoV‐2 was detected in the CSF through reverse transcriptase polymerase chain reaction, but not in nasopharyngeal, tracheal secretion and rectal samples. Brain magnetic resonance imaging showed lesions on white matter hemispheres, the body and splenium of the corpus callosum and resembling the projection of corticospinal tract, remarkably on cerebellar peduncles.
Conclusions
This demonstrates the challenges in diagnosing COVID‐19 in patients with neurological presentations.
Brain magnetic resonance imaging evolution image of COVID‐19 meningo‐encephalitis.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• There is large interindividual variability in the pharmacokinetics of protease inhibitors (PIs) among human immunodeficiency virus (HIV)‐infected ...individuals under highly active antiretroviral therapy.
• Protease inhibitor have been recently reported to be substrates of the SLCO1B1/OATP1 drug transporter.
• A single nucleotide polymorphism (SNP) in the SLCO1B1 gene (521T→C) was associated with plasma levels of lopinavir in HIV‐infected individuals.
WHAT THIS STUDY ADDS
• Data on the impact of three SLCO1B1 SNPs (521T→C, 388A→G, 463C→A) on the trough plasma concentration of lopinavir and ritonavir in a cohort of 99 adult HIV‐infected Brazilian men under stable highly active antiretroviral therapy.
• Evidence that carriers of the 521C allele display significantly higher lopinavir, but not ritonavir plasma concentrations relative to the wild‐type TT genotype.
• No effect of either 388A→G or 463C→A SNPs on lopinavir or ritonavir plasma concentrations.
• Further studies are required to confirm the clinical significance of the association between the SLCO1B1521T→C polymorphism and lopinavir pharmacokinetics.
AIMS To investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388A→G, 463C→A, 521T→C) and lopinavir/ritonavir plasma concentrations.
METHODS The study included 99 human immunodeficiency virus‐infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography–tandem mass spectrometry. Genotyping of SLCO1B1388A→G, 463C→A and 521T→C polymorphisms was performed by allelic discrimination using real‐time polymerase chain reaction.
RESULTS The trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521T→C genotypes (P= 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P= 0.02). Carriers of the 521C allele display significantly higher lopinavir plasma concentrations relative to the wild‐type TT genotype (P= 0.03).
CONCLUSIONS Reduced uptake of lopinavir by hepatocytes in carriers of the 521C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.
Abstract We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara MVA and fowlpox FPV) in a homologous and heterologous vector prime-boost vaccination regimen containing matching ...HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (109 pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60 (8.3%) of participants, respectively, and IFN-γ ELISpot responses in 28/62 (45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.
Lopinavir and ritonavir are frequently included in highly active antiretroviral therapy (HAART) regimens for HIV infection. These drugs are substrates, and may also inhibit and/or induce the ...P-glycoprotein (ABCB1) transporter, encoded by the polymorphic ABCB1 gene. We investigated the impact of three common exonic ABCB1 polymorphisms on the concentrations of lopinavir and ritonavir in blood, semen and saliva of HIV-infected men under stable HAART containing ritonavir-boosted lopinavir.
Blood, semen and saliva samples were collected from 113 subjects, 30-35 minutes before the scheduled morning dose of lopinavir/ritonavir, and trough drug concentrations were measured using LC/MS/MS. The 1236C>T, 2677G>T/A and 3435C>T polymorphisms were genotyped using the single base extension-termination method and ABCB1 haplotypes were statistically inferred.
Median (25th-75th percentile) trough concentrations (ng/ml) of lopinavir in plasma, semen and saliva were 6326 (4070-8617), 286.0 (128.4-475.5) and 72.7 (38.0-119.6), respectively. The corresponding concentrations (ng/ml) for ritonavir were 261.8 (172.2-398.6), 17.7 (9.2-27.6) and 5.3 (3.2-9.0), respectively. Univariate and multivariate regression analysis revealed no influence of ABCB1 genotypes or haplotypes on the concentrations of lopinavir and ritonavir in plasma, semen and saliva of HIV-infected men under stable HAART treatment.
The ABCB1 1236C>T, 2667G>T/A and 3435C>T genotypes and haplotypes are not predictors of lopinavir and ritonavir concentrations in blood plasma, semen or saliva of HIV-infected men under stable HAART treatment. The concentrations of lopinavir and ritonavir in saliva are not reliable predictors of the concentration of these drugs in semen.
Mixture models for quantitative HIV RNA data Moulton, Lawrence H; Curriero, Frank C; Barroso, Paulo F
Statistical methods in medical research,
08/2002, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Clinical investigators are increasing their use of quantitative determinations of HIV viral load in their study populations. The distributions of these measures may be highly skewed, left-censored, ...and with an extra spike below the detection limit of the assay. We recommend use of a mixture model in this situation, with two sets of explanatory covariates. We extend this model to incorporate multiple measures across time, and to employ shared parameters as a way of increasing model efficiency and parsimony. Data from a cohort of HIV-infected men are used to illustrate these features, and simulations are performed to assess the utility of shared parameters.
CONTEXT:Long-term adherence to antiretrovirals is critical for sustained virologic response to HIV therapy in blood. Although antiretroviral therapy (ART) reduces HIV seminal shedding, little is ...known about the relationship between adherence to ART and HIV suppression in semen.
OBJECTIVE:To determine predictors of seminal HIV RNA suppression after 6 months of ART.
DESIGN:Prospective observational cohort of 93 HIV-infected subjects before and after introduction of ART. Seminal HIV RNA was measured at baseline and 1, 2, 3, and 6 months after the introduction of therapy. Adherence to therapy was measured by self-report.
SETTING:A large academic HIV reference center in Rio de Janeiro, Brazil.
MAIN OUTCOME MEASURE:Detectable HIV RNA in semen.
RESULTS:In a multivariate logistic model with undetectable seminal HIV RNA after 6 months of therapy as the outcome variable, adjusting for baseline seminal viral load, both being adherent to therapy (OR = 11.8, P < 0.01) and using triple-drug ART (OR = 6.48, P = 0.04) were independently associated with seminal HIV RNA suppression.
CONCLUSIONS:Inability to adhere to therapy was strongly associated with persistent shedding of HIV RNA in semen. Measures to improve adherence are urgently needed to reduce the sexual spread of potentially drug-resistant HIV among subjects using antiretrovirals.
PURPOSE:Reliable predictors of HIV disease progression are scarce in developing countries, where most HIV infections occur. We describe early virologic and immunologic events among men who have sex ...with men in Rio de Janeiro, Brazil.
METHODS:Seroconverters from 2 high-risk cohorts were followed for up to 36 months with periodic laboratory evaluations, plasma viral load, and CD4 count assessments. Viral load and CD4 count mean trajectories were computed. For the modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720 (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was 373 cells/μL (range 260-508). Overall variation on viral loads ranged from 4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at approximately 600 days (n = 12) after estimated time of seroconversion. The initial period of HIV infection was characterized by an increase in CD4 count (n = 29) followed by a steep decline starting at approximately 200 days (508 cells, 95% CI425 to 569). A gradual decrease was observed in the median CD4 count thereafter, reaching 281 (95% CI100 to 466) at 1000 days after the estimated date of seroconversion.
CONCLUSIONS:Although viral load dynamics resembled those observed in developed countries, CD4 counts seem to decline at a faster rate than in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data are needed to assess the impact of interventions, such as antiretroviral therapy, on the clinical course of HIV infection in Brazil.
In individuals who are infected with human immunodeficiency virus (HIV), distributions of quantitative HIV ribonucleic acid measurements may be highly left censored with an extra spike below the ...limit of detection LD of the assay. A two-component mixture model with the lower component entirely supported on 0, LD is recommended to model the extra spike in univariate analysis better. Let$LD_1$, and$LD_2$be the limits of detection for the two HIV viral load measurements. When estimating the correlation coefficient between two different measures of viral load obtained from each of a sample of patients, a bivariate Gaussian mixture model is recommended to model the extra spike on$\lbrack 0, LD_1\rbrack$and$\lbrack 0, LD_2\rbrack$better when the proportion below LD is incompatible with the left-hand tail of a bivariate Gaussian distribution. When the proportion of both variables falling below LD is very large, the parameters of the lower component may not be estimable since almost all observations from the lower component are falling below LD. A partial solution is to assume that the lower component's entire support is on$\lbrack 0, LD_1\rbrack x \lbrack 0, LD_2\rbrack$. Maximum likelihood is used to estimate the parameters of the lower and higher components. To evaluate whether there is a lower component, we apply a Monte Carlo approach to assess the p-value of the likelihood ratio test and two information criteria: a bootstrap-based information criterion and a cross-validation-based information criterion. We provide simulation results to evaluate the performance and compare it with two ad hoc estimators and a single-component bivariate Gaussian likelihood estimator. These methods are applied to the data from a cohort study of HIV-infected men in Rio de Janeiro, Brazil, and the data from the Women's Interagency HIV oral study. These results emphasize the need for caution when estimating correlation coefficients from data with a large proportion of non-detectable values when the proportion below LD is incompatible with the left-hand tail of a bivariate Gaussian distribution.
We report the accidental needlestick inoculation of a laboratory worker with vaccinia virus. Although the patient had previously been vaccinated against smallpox, severe lesions appeared on the ...fingers. Western blot and polymerase chain reaction-restriction fragment length polymorphism were used to analyze the virus recovered from the lesions. The vaccinia virus-specific immunoglobulin G levels were measured by enzyme-linked immunosorbent assay. Our study supports the need for vaccination for laboratory workers that routinely handle orthopoxvirus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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