Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
1.
Genes (Basel) ; 12(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34573296

RESUMO

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2-9 years, 100% ART-experienced), 47 adolescents (age 10-18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.

2.
Glob Health Action ; 14(1): 1947566, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34404330

RESUMO

BACKGROUND: There are limited data to help guide implementation of differentiated HIV service delivery (DSD) in resource-limited settings in sub-Saharan Africa. OBJECTIVES: This pre-implementation study sought to assess the proportion of patients eligible for DSD and HIV services utilization, as well as risk factor analysis of virologic failure in Sierra Leone. METHODS: We conducted a retrospective study of adult HIV-infected patients aged 18 years and older receiving care at the largest HIV treatment center in Sierra Leone 2019-2020. Multiple logistic regression was used to identify predictors of virologic failure. RESULTS: Of 586 unique patients reviewed, 210 (35.8%) qualified as 'stable' for antiretroviral therapy (ART) delivery. There was high utilization of certain HIV service programs (e.g. HIV status disclosure to partners (83%) and treatment 'buddy' program participation (62.8%)), while other service programs (e.g. partner testing and community HIV support group participation) had low utilization (<50%). Of 429 patients with available viral load, 277 (64.6%) were virologically suppressed. In the multivariate logistic regression analysis of risk factors of virologic failure, CD4 < 350 cells/mm3 (p = 0.009), atazanavir-based ART (p = 0.032), once monthly versus once two- or three-monthly ART dispensing (p = 0.028), history of ART switching (p = 0.02), poor adherence (p = 0.001) and not having received adherence support (p < 0.001) were independent predictors of virologic failure. CONCLUSION: Approximately one in three HIV-infected patients on ART were eligible for DSD. We identified gaps in HIV care (i.e. low partner testing, treatment 'buddy', program participation and a substantially high rate of virologic failure) that need to be addressed in preparation for full implementation of DSD in Sierra Leone.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Fármacos Anti-HIV/uso terapêutico , Utilização de Instalações e Serviços , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Retrospectivos , Serra Leoa , Carga Viral
3.
Trop Med Infect Dis ; 6(3)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34449755

RESUMO

The COVID-19 pandemic has adversely affected tuberculosis (TB) care delivery in high burden countries. We therefore conducted a retrospective study to assess the impact of COVID-19 on TB case detection and treatment outcomes at the Chest Clinic at Connaught Hospital in Freetown, Sierra Leone. Overall, 2300 presumptive cases were tested during the first three quarters of 2020 (intra-COVID-19) versus 2636 in 2019 (baseline), representing a 12.7% decline. Testing declined by 25% in women, 20% in children and 81% in community-initiated referrals. Notwithstanding, laboratory-confirmed TB cases increased by 37.0% and treatment success rate was higher in 2020 (55.6% vs. 46.7%, p = 0.002). Multivariate logistic regression analysis found that age < 55 years (aOR 1.74, 95% CI (1.80, 2.56); p = 0.005), new diagnosis (aOR 1.69, 95% CI (1.16, 2.47); p = 0.007), pulmonary TB (aOR 3.17, 95% CI (1.67, 6.04); p < 0.001), HIV negative status (aOR 1.60, 95%CI (1.24, 2.06); p < 0.001) and self-administration of anti-TB drugs through monthly dispensing versus directly observed therapy (DOT) (aOR 1.56, 95% CI (1.21, 2.03); p = 0.001) independently predicted treatment success. These findings may have policy implications for DOTS in this setting and suggest that more resources are needed to reverse the negative impact of the COVID-19 pandemic on TB program activities in Sierra Leone.

4.
Int J Nanomedicine ; 16: 4813-4830, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290504

RESUMO

Human coronaviruses present a substantial global disease burden, causing damage to populations' health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses-playing multiple essential roles in virus infection and immunity. Studying and understanding virus glycans at the nanoscale provide new insights into the diagnosis and treatment of viruses. Glycan nanostructures are considered potential targets for molecular diagnosis, antiviral therapeutics, and the development of vaccines. This review article describes glycan nanostructures (eg, glycoproteins and glycolipids) that exist in cells, subcellular structures, and microbes. We detail the structure, characterization, synthesis, and functions of virus glycans. Furthermore, we describe the glycan nanostructures of different human coronaviruses, such as human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), the Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and how glycan nanotechnology can be useful to prevent and combat human coronaviruses infections, along with possibilities that are not yet explored.


Assuntos
Betacoronavirus/química , Nanoestruturas/análise , Nanoestruturas/química , Polissacarídeos/análise , Polissacarídeos/química , Humanos
5.
J Acquir Immune Defic Syndr ; 87(2): 789-793, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587502

RESUMO

BACKGROUND: Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, viral DNA shedding and/or ulcers) preceded HIV acquisition in the hormonal contraception and HIV cohort. METHODS: Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) at each visit. RESULTS: Of 387 HSV-2 seropositive women, most had prevalent as compared with incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, P < 0.01). Shedding occurred around HIV acquisition (t-3months aOR, 2.7; 95% CI, 0.8 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%; P = 0.06) and detection was after HIV acquisition (t+6months aOR, 14.5; 95% CI, 1.6 to 133.9). CONCLUSIONS: HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.


Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/epidemiologia , Herpes Genital/epidemiologia , Eliminação de Partículas Virais , Adolescente , Adulto , Feminino , Soropositividade para HIV/sangue , HIV-1/imunologia , Herpesvirus Humano 2/imunologia , Humanos , Úlcera/diagnóstico , Úlcera/virologia , Adulto Jovem , Zimbábue/epidemiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-33168615

RESUMO

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with fub). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.


Assuntos
Acinetobacter baumannii , Minociclina , Adulto , Animais , Antibacterianos/uso terapêutico , Estado Terminal , Humanos , Testes de Sensibilidade Microbiana
7.
Int J Infect Dis ; 102: 45-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33002619

RESUMO

OBJECTIVE: To assess the prevalence of serological markers of HBV and endemic acute and chronic infections (HAV, HCV, CMV, HTLV-1/2 and syphilis) in HIV-infected children, adolescents and pregnant women in Sierra Leone. METHOD: We conducted a cross-sectional study at the national children's and women's hospitals in Freetown. Logistic regression was used to assess predictors of HBsAg positivity. RESULTS: 183 HIV-infected participants were enrolled, comprising children (n = 88), adolescents (n = 47) and pregnant women (n = 48). All participants (100%) were CMV IgG-positive, while 56.8%, 93.6% and 100% of children, adolescents and pregnant women, respectively, were HAV IgG-positive. The prevalence of HCV, HTLV-1/2 and syphilis were <4%. HBV markers were distributed as follows-children: HBsAg (2.3%), HBeAg (0%), anti-HBc (5.7%); adolescents: HBsAg (17.0%), HBeAg (6.4%), anti-HBc (27.7%); and pregnant women: HBsAg (18.8%), HBeAg (4.2%), anti-HBc (77.1%). Age >10 years, i.e., being born pre-2009 before implementation of routine hepatitis B immunization (aOR 5.05 [1.18-21.28]; p = 0.029) and CD4 count <350 cells/mm3 (aOR 3.97 [1.07-14.71]; p = 0.039) predicted HBsAg positivity. CONCLUSION: A high burden of chronic HBV and other endemic infections was observed among HIV-infected patients born pre-2009 before implementation of routine HBV immunization in Sierra Leone, warranting targeted screening and immunization of this high-risk population.


Assuntos
Infecções por HIV/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B/epidemiologia , Sífilis/epidemiologia , Adolescente , Adulto , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/complicações , Hepatite B/complicações , Humanos , Masculino , Gravidez , Gestantes , Prevalência , Serra Leoa/epidemiologia , Sífilis/complicações , Adulto Jovem
8.
IDCases ; 20: e00778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341910

RESUMO

People exposed to COVID-19 have a risk of developing disease, and health care workers are at risk at a time when they are badly needed during a health care crisis. Hydroxychloroquine and chloroquine have been used as treatment and are being considered as prophylaxis. Our patient developed COVID-19 while on hydroxychloroquine and although more work is needed, this calls into question the role of these medications as preventive therapy.

9.
Int J Infect Dis ; 96: 112-118, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32339724

RESUMO

OBJECTIVE: To assess the diagnosis, treatment outcomes, and predictors of mortality in adult tuberculosis (TB) patients in an urban setting with a high HIV prevalence. METHODS: A retrospective study was conducted of adult TB patients aged ≥15 years who were treated at Connaught Hospital in Freetown, Sierra Leone from January through December 2017. Multivariate logistic regression was used to identify predictors of mortality. RESULTS: Of 1127 TB cases notified in 2017, 1105 (98%) were tested for HIV, yielding a TB/HIV co-infection rate of 32.0%. Only HIV-tested cases (n=1105) were included in the final analysis. The majority were male (69.3%), aged 25-34 years (29.2%), and had pulmonary TB (96.3%). Treatment outcomes were as follows: 29.0% cured, 29.0% completed, 0.5% treatment failure, 24.2% lost to follow-up, 12.8% transferred/not evaluated, and 4.5% died. The majority of deaths (80.0%, 40/50) occurred within 2 months of TB treatment initiation. Age 65 years or older (adjusted odds ratio 3.48, 95% confidence interval 1.15-10.56; p=0.027) and HIV-positive status (adjusted odds ratio 3.50, 95% confidence interval 1.72-7.12; p=0.001) were independent predictors of mortality. CONCLUSIONS: Suboptimal TB treatment outcomes were observed in Sierra Leone in 2017. More local and international action is warranted to help achieve the 2035 global TB elimination targets.


Assuntos
Tuberculose/diagnóstico , Tuberculose/terapia , Adolescente , Adulto , Idoso , Cidades , Coinfecção/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Serra Leoa/epidemiologia , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/mortalidade , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
10.
Open Forum Infect Dis ; 7(1): ofz514, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31988972

RESUMO

Background: The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin's shape and charge profile uniquely impact its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin with moxifloxacin for the treatment of CABP. Methods: A randomized, double-blind, comparator-controlled, multicenter, global phase 3 study compared the efficacy and safety of delafloxacin 300 mg twice daily or moxifloxacin 400 mg once daily in adults with CABP. The primary end point was early clinical response (ECR), defined as improvement at 96 (±24) hours after the first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. Results: In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events that were considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. Conclusions: Intravenous/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for Gram-positive, Gram-negative, and atypical pathogens. ClinicalTrialsgov Identifier: NCT03534622.

11.
PLoS One ; 15(1): e0224359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914129

RESUMO

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of ß-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1ß-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.


Assuntos
Disbiose/imunologia , Imunidade Inata/genética , Doenças Sexualmente Transmissíveis/imunologia , Vaginose Bacteriana/imunologia , Adolescente , Adulto , Biomarcadores/metabolismo , Colo do Útero/imunologia , Colo do Útero/microbiologia , Colo do Útero/patologia , Disbiose/epidemiologia , Disbiose/microbiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Estresse Oxidativo/imunologia , Gravidez , Infecções do Sistema Genital/epidemiologia , Infecções do Sistema Genital/imunologia , Inibidor Secretado de Peptidases Leucocitárias/imunologia , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Doenças Sexualmente Transmissíveis/epidemiologia , Doenças Sexualmente Transmissíveis/microbiologia , Uganda/epidemiologia , Vagina/imunologia , Vagina/microbiologia , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zimbábue/epidemiologia
12.
J Glob Antimicrob Resist ; 21: 171-180, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31600598

RESUMO

OBJECTIVES: Successful decolonisation of nasal Staphylococcus aureus (SA) carriage by mupirocin is limited by increasing drug resistance. This randomised, open-label, phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial with rapid intrinsic activity against SA. METHODS: The study was performed in 60 healthy adults. In Part 1, eight non-SA carriers were randomised to groups of four subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel or 2.0mg/g 2% gel. In Part 2, 52 persistent SA carriers were randomised to groups of 13 subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel, 2.0mg/g 2% gel, 0.5mg/g 4% gel or 4% viscosified placebo gel. Plasma pharmacokinetic and pharmacodynamic studies were performed. Antistaphylococcal activity was assessed as the presence/absence of SA and by quantification of colonisation using a semiquantitative scale (SA score). RESULTS: 56 subjects (8/8 from Part 1 and 48/52 from Part 2) completed the study, with 47/60 comprising the pharmacokinetic population and 48/60 the pharmacodynamic population. There was no measurable systemic absorption of XF-73. XF-73 treatment was associated with rapid reduction in SA score in all subjects. The most common treatment-emergent adverse events (TEAEs) were rhinorrhoea and nasal dryness (15.5% each in Parts 1 and 2). TEAEs were mild and resolved spontaneously. CONCLUSION: XF-73 was well tolerated with minimal side effects at doses of 0.5mg/g 2% gel and 2.0mg/g 2% gel. These findings support further development of XF-73.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Adulto , Antibacterianos/efeitos adversos , Humanos , Mupirocina , Nariz , Infecções Estafilocócicas/tratamento farmacológico
13.
Clin Infect Dis ; 70(9): 1826-1833, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31219148

RESUMO

BACKGROUND: Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSIs). We determined whether the PBS predicts 14-day inpatient mortality in nonbacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections. METHODS: Patients were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacteriaceae, a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS. RESULTS: In a cohort of 475 patients with CRE infections, a PBS ≥4 was associated with mortality in patients with nonbacteremia infections (risk ratio [RR], 21.9; 95% confidence interval [CI], 7.0, 68.8) and with BSIs (RR, 6.0; 95% CI, 2.5, 14.4). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature <36.0°C vs ≥36°C was independently associated with mortality. A qPitt score ≥2 had similar discrimination as a PBS ≥4 in nonbacteremia infections. CONCLUSIONS: Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in nonbacteremia CRE infections.


Assuntos
Bacteriemia , Infecções por Enterobacteriaceae , Infecções por Klebsiella , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
14.
BMC Public Health ; 19(1): 1320, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638941

RESUMO

BACKGROUND: HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk. METHODS: We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown-the main referral hospital in Sierra Leone-from July through September 2017, to assess associated factors and predictors of HIV-related mortality. RESULTS: One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/µL (IQR 25-266), and was further staged as severe immunosuppression: CD4 < 100 cells/µL (50%, 56/112); AIDS: CD4 < 200 cells/µL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/µL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02-0.65]; p = 0.01) emerged as an independent predictor of mortality. CONCLUSION: HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.


Assuntos
Infecções por HIV/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Encaminhamento e Consulta , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Serra Leoa/epidemiologia , Adulto Jovem
15.
J Pharm Biomed Anal ; 176: 112775, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31446299

RESUMO

This article describes the simultaneous determination of bedaquiline fumarate (TMC-207) and rifabutin in human plasma by stable isotope dilution tandem mass spectrometry. The methodology was developed for an investigation of potential drug-drug interactions of the two anti-tuberculosis drugs when given together to healthy human volunteers. Use of the two drugs in combination to treat disease caused by Mycobacterium tuberculosis is contemplated as the bacterium becomes resistant to many currently available drugs.


Assuntos
Antituberculosos/sangue , Diarilquinolinas/sangue , Monitoramento de Medicamentos/métodos , Rifabutina/sangue , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Diarilquinolinas/administração & dosagem , Diarilquinolinas/farmacocinética , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Rifabutina/administração & dosagem , Rifabutina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Tuberculose/tratamento farmacológico
16.
Am J Trop Med Hyg ; 100(6): 1521-1524, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30938283

RESUMO

HIV coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) is common because of shared transmission routes. There is no published data on the prevalence of these infections in people living with HIV in Sierra Leone. We conducted a cross-sectional study of 211 HIV-positive patients aged ≥ 18 years in Freetown, Sierra Leone, in November 2017. Plasma samples were analyzed using the chemiluminescent microparticle immunoassay (Architect System, Abbott ARCHITECT Analyzer, Abbott Park, IL. The majority were female (63.5%), with median age 36 years (interquartile range [IQR]: 32-44) and median CD4 count of 396 cells/µL (IQR: 214-534). Sixty patients (28.4%) were newly diagnosed and antiretroviral therapy (ART) naive; 151 patients (71.6%) were ART experienced. The prevalence of the hepatitis B surface antigen (HBsAg), total anti-hepatitis B core antibody, and anti-HCV was 21.7%, 82.9%, and 4.3%, respectively. No cases of HTLV-1 or HTLV-2 were detected. Male gender (P = 0.004) and CD4 < 350 cells/µL (P = 0.017) were associated with the HBsAg positive status.


Assuntos
Infecções por HIV/complicações , Infecções por HTLV-I/complicações , Infecções por HTLV-II/complicações , Hepatite B/complicações , Hepatite C/complicações , Adulto , Contagem de Linfócito CD4 , Coinfecção , Feminino , Infecções por HIV/epidemiologia , Infecções por HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/sangue , Infecções por HTLV-II/epidemiologia , Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite C/sangue , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Serra Leoa/epidemiologia , Adulto Jovem
17.
J Antimicrob Chemother ; 74(7): 2024-2029, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30989237

RESUMO

OBJECTIVES: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. PATIENTS AND METHODS: We conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list. RESULTS: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. CONCLUSIONS: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.


Assuntos
Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/genética , Humanos , Masculino , Mutação , Prevalência , Vigilância em Saúde Pública , Serra Leoa/epidemiologia , Carga Viral
18.
Open Forum Infect Dis ; 6(1): ofy351, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30631796

RESUMO

In the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), trimethoprim-sulfamethoxazole (TMP-SMX) had a limited role in the treatment of less severe carbapenem-resistant Enterobacteriaceae (CRE) infections, especially urinary tract infections. Of tested CRE, only 29% were susceptible to TMP-SMX. Development of resistance further limits the use of TMP-SMX in CRE infections.

19.
West J Nurs Res ; 41(7): 990-1008, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30654713

RESUMO

People living with HIV (PLHIV) are increasingly diagnosed with comorbidities which require increasing self-management. We examined the effect of a self-management intervention on neurocognitive behavioral processing. Twenty-nine PLHIV completed a two-group, 3-month randomized clinical trial testing a self-management intervention to improve physical activity and dietary intake. At baseline and 3 months later, everyone completed validated assessments of physical, diet, and neurocognitive processing (functional magnetic resonance imaging [fMRI]-derived network analyses). We used linear mixed effects modeling with a random intercept to examine the effect of the intervention. The intervention improved healthy eating (p = .08) but did not improve other self-management behaviors. There was a significant effect of the intervention on several aspects of neurocognitive processing including in the task positive network (TPN) differentiation (p = .047) and an increase in the default mode network (DMN) differentiation (p = .10). Self-management interventions may influence neurocognitive processing in PLHIV, but those changes were not associated with positive changes in self-management behavior.


Assuntos
Cognição , Infecções por HIV/terapia , Promoção da Saúde , Autogestão , Actigrafia/estatística & dados numéricos , Adulto , Dieta , Exercício Físico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Obesidade
20.
Clin Infect Dis ; 68(7): 1144-1151, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30289485

RESUMO

BACKGROUND: Postmenopausal women have unique sociobiological human immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics, and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus placebo in postmenopausal women. METHODS: We enrolled 96 HIV-negative postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We assessed safety by adverse events (AEs). DPV concentrations were quantified in plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and 12 weeks using repeated measures ANOVA. We assessed acceptability by self-report. RESULTS: We found no differences in the proportion of women with related grade 2 or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P = .68) or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P = .57). In the DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high; 84/93 (90%) "very much liked or liked" the VR. CONCLUSIONS: DPV VRs were safe, well tolerated, and acceptable in postmenopausal women. Plasma concentrations were comparable to published data on DPV use in reproductive-age women (median plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic data, the DPV VR is promising for preexposure prophylaxis in postmenopausal women. CLINICAL TRIALS REGISTRATION: NCT02010593.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Dispositivos Anticoncepcionais Femininos , Pós-Menopausa , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Idoso , Fármacos Anti-HIV/administração & dosagem , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Placebos/administração & dosagem , Plasma/química , Pirimidinas/administração & dosagem , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...