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1.
Proc Natl Acad Sci U S A ; 119(22): e2122769119, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35617431

RESUMO

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2­ and HeV G/F­mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus Hendra , Fragmentos Fab das Imunoglobulinas , Proteínas do Envelope Viral , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Cristalografia por Raios X , Epitopos/química , Epitopos/genética , Vírus Hendra/genética , Vírus Hendra/imunologia , Humanos , Fragmentos Fab das Imunoglobulinas/química , Testes de Neutralização , Profilaxia Pós-Exposição , Domínios Proteicos , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
2.
AIDS Care ; 34(11): 1443-1451, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35473429

RESUMO

HIV incidence is high and persistent among cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men, particularly among those who sell or trade sex. In preparation for an open-label combination HIV pre-exposure prophylaxis (PrEP) program for these groups, we conducted formative research to explore the context of sex work/trade and factors that affect implementation of PrEP interventions. This study analyzed interviews with 20 young (aged 18-26 years) MSM and TGW who sell/trade sex and three sex work venue managers in Bangkok and Pattaya, Thailand. Participants described diverse contexts of sex work/trade, including in multiple informal and formal sex venues. Several participants reported mobility across provinces and out of the country, which led to intermittent sex work/trade. TGW sex workers reported challenges with access and cost of femininizing hormones and limited employment opportunities. Factors that could facilitate or challenge PrEP program implementation included HIV stigma, the role of venue management in sexual health practice, lack of PrEP knowledge, lower perceived HIV risk, and interest in personal health and wellbeing. Program implementers must consider myriad factors to successfully implement PrEP among young MSM and TGW engaged in sex work or trade in Thailand.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Pessoas Transgênero , Masculino , Humanos , Feminino , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fatores Sociais , Tailândia/epidemiologia , Fármacos Anti-HIV/uso terapêutico
3.
AIDS Care ; 34(10): 1305-1313, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34424784

RESUMO

We assessed HIV and syphilis infection among MSM and TGW attending Silom Community Clinic from 2017 to 2019. Walk-in and referral clients completed a registration application including a question on gender identity. We compared the prevalence of HIV, syphilis, and HIV and syphilis coinfection among TGW and MSM. In a total of 1050 clients, 276 (26.3%) were TGW and 774 (74.7%) were MSM. Among TGW clients, HIV prevalence was 29.8%, syphilis prevalence was 38.4%, and coinfection prevalence was 18.5%. Comparing prevalence among TGW to MSM, the adjusted prevalence ratio (aPR) for HIV was 1.8 (95% CI:1.4-2.3), for syphilis was 1.2 (95% CI:1.0-1.4), and for HIV and syphilis coinfection was 2.1 (95% CI:1.4-2.9). The prevalence of syphilis was higher than HIV among TGW, with a PR of 1.3 (95% CI:1.1-1.6), and among MSM, with a PR of 1.4 (95% CI:1.2-1.7). TGW age 15-21 years had an HIV prevalence of 16.9% and syphilis prevalence of 30.8%. After adjusting for age, referral, and sexual behaviors, TGW remain significantly associated with HIV and syphilis prevalence. There is a substantial burden of HIV and HIV/syphilis co-infection among TGW. HIV/STI prevention are needed for TGW, including linkage to HIV care.


Assuntos
Coinfecção , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Pessoas Transgênero , Adolescente , Adulto , Coinfecção/epidemiologia , Feminino , Identidade de Gênero , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/epidemiologia , Tailândia/epidemiologia , Adulto Jovem
4.
Ethos ; 50(2): 208-232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36337726

RESUMO

This case study provides a critical discourse analysis of 121 letters of complaint and self-advocacy authored by Natasha Keating, a trans woman incarcerated in two Australian male correctional facilities from 2000 to 2007. During her incarceration, Natasha experienced victimization, misgendering, microaggression, and institutional discrimination. Despite this, Natasha embodied and "fought" against the injustices she experienced, whilst seeking to speak for other trans incarcerated persons also silenced and treated with indifference, contributing to changes in the carceral system. This original case study analyzes the discursive strategies Natasha employed to construct and reclaim an affirming self-identity through a deliberate campaign to effect social change and policy concessions within a system designed to curtail self-determination. Through her empathic and impassioned letter-writing approach, leveraging a military metaphor, this novel analysis showcases the significant implications her activism/agentism and determination had in naming and seeking to dismantle the systems of oppression trans incarcerated women experience.

5.
BMC Cancer ; 21(1): 494, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941111

RESUMO

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Movimentos dos Órgãos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Austrália , Carcinoma Hepatocelular/secundário , Dinamarca , Marcadores Fiduciais , Humanos , Neoplasias Hepáticas/secundário , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Respiração , Resultado do Tratamento
6.
BMC Infect Dis ; 17(1): 115, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28148232

RESUMO

BACKGROUND: Although Mycobacterium tuberculosis (TB) infection may cause extrapulmonary disease in HIV-infected adults, HIV-associated hepatic TB has been poorly characterized. Our objective was to describe hepatic TB in HIV-infected adults. METHODS: Retrospective study of patients diagnosed with hepatic TB from 2005-2012 at Infectious Diseases Clinic, King Edward VIII Hospital, Durban, South Africa. RESULTS: Among twenty cases of histology-confirmed HIV-associated hepatic TB, median CD4 count was 47 cells/µl (inter-quartile range 27-107 cells/µl) and 75% (15/20) of patients had pre-existing pulmonary TB. The most frequent clinical finding was hepatomegaly (85%). Liver enzyme abnormalities included elevated alkaline phosphatase (median 456 u/L, inter-quartile range 322-1,043 u/L) and gamma-glutamyltransferase (median 422 u/L, inter-quartile range 235-736 u/L). Acid-fast bacilli were cultured from liver tissue in 30% (6/20) of patients; 25% (5/20) identified as TB. With standard anti-TB therapy, liver enzymes improved within six months in 92% (11/12) of patients. One year after diagnosis, twelve patients resolved clinically, two patients developed drug-resistant TB and six patients died. CONCLUSION: In our case series of HIV-infected patients, hepatic TB occurred in patients with severe immunosuppression, who presented with hepatomegaly and abnormal liver enzymes. More than half of patients had resolution of liver function by six months however the 12-month mortality remained high.


Assuntos
Infecções por HIV/complicações , Tuberculose Hepática/complicações , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Estudos Retrospectivos , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Pulmonar/complicações , Adulto Jovem
7.
J Infect Dis ; 213(3): 448-55, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26357909

RESUMO

Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.


Assuntos
Anticorpos Monoclonais/imunologia , Infecções por Henipavirus/virologia , Henipavirus/genética , Henipavirus/fisiologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/imunologia , Cricetinae , Feminino , Aptidão Genética , Henipavirus/imunologia , Infecções por Henipavirus/imunologia , Humanos , Mesocricetus , Camundongos , Mutação , Testes de Neutralização
8.
BMC Infect Dis ; 15: 209, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25943103

RESUMO

BACKGROUND: Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a result of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to characterize the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB and to comment on the impact of HIV co-infection on these characteristics. METHODS: We conducted a systematic literature search in PubMed and ScienceDirect for articles pertaining to hepatic TB with human subjects from 1960 to July 2013. RESULTS: We obtained data on 618 hepatic TB patients from 14 case series. The most common reported signs and symptoms were hepatomegaly (median: 80%, range: 10-100%), fever (median: 67%, range: 30-100), respiratory symptoms (median: 66%, range: 32-78%), abdominal pain (median: 59.5%, range: 40-83%), and weight loss (median: 57.5%, range: 20-100%). Common laboratory abnormalities were elevated alkaline phosphatase and gamma-glutamyl transferase. Ultrasound and computerized tomography (CT) were sensitive but non-specific. On liver biopsy, smear microscopy for acid-fast bacilli had a median sensitivity of 25% (range: 0-59%), histology of caseating granulomas had a median sensitivity of 68% (range: 14-100%), and polymerase chain reaction for TB had a median sensitivity of 86% (range: 30-100%). Standard anti-tuberculous chemotherapy for 6 to 12 months achieved positive outcomes for nearly all patients with drug-susceptible TB. CONCLUSIONS: Clinicians in TB-endemic regions should maintain a high index of suspicion for hepatic TB in patients presenting with hepatomegaly, fever, respiratory symptoms, and elevated liver enzymes. The most sensitive imaging modality is a CT scan, while the most specific diagnostic modality is a liver biopsy with nucleic acid testing of liver tissue samples. Upon diagnosis, 4-drug anti-TB therapy should promptly be initiated. HIV co-infected patients may have more complex cases and should be closely monitored for complications.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Mycobacterium tuberculosis , Tuberculose Hepática/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Coinfecção , Saúde Global , Humanos , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Tuberculose Hepática/complicações , Tuberculose Hepática/diagnóstico , Tuberculose Hepática/tratamento farmacológico
9.
Artigo em Inglês | MEDLINE | ID: mdl-38698577

RESUMO

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

10.
PLoS One ; 19(7): e0305296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968209

RESUMO

BACKGROUND: Quality assessments of gonococcal surveillance data are critical to improve data validity and to enhance the value of surveillance findings. Detecting data errors by systematic audits identifies areas for quality improvement. We designed and implemented an internal audit process to evaluate the accuracy and completeness of surveillance data for the Thailand Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP). METHODS: We conducted a data quality audit of source records by comparison with the data stored in the EGASP database for five audit cycles from 2015-2021. Ten percent of culture-confirmed cases of Neisseria gonorrhoeae were randomly sampled along with any cases identified with elevated antimicrobial susceptibility testing results and cases with repeat infections. Incorrect and incomplete data were investigated, and corrective action and preventive actions (CAPA) were implemented. Accuracy was defined as the percentage of identical data in both the source records and the database. Completeness was defined as the percentage of non-missing data from either the source document or the database. Statistical analyses were performed using the t-test and the Fisher's exact test. RESULTS: We sampled and reviewed 70, 162, 85, 68, and 46 EGASP records during the five audit cycles. Overall accuracy and completeness in the five audit cycles ranged from 93.6% to 99.4% and 95.0% to 99.9%, respectively. Overall, completeness was significantly higher than accuracy (p = 0.017). For each laboratory and clinical data element, concordance was >85% in all audit cycles except for two laboratory data elements in two audit cycles. These elements significantly improved following identification and CAPA implementation. DISCUSSION: We found a high level of data accuracy and completeness in the five audit cycles. The implementation of the audit process identified areas for improvement. Systematic quality assessments of laboratory and clinical data ensure high quality EGASP surveillance data to monitor for antimicrobial resistant Neisseria gonorrhoeae in Thailand.


Assuntos
Confiabilidade dos Dados , Gonorreia , Neisseria gonorrhoeae , Tailândia/epidemiologia , Humanos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação , Gonorreia/epidemiologia , Gonorreia/microbiologia , Gonorreia/tratamento farmacológico , Gonorreia/diagnóstico , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/normas , Bases de Dados Factuais , Vigilância da População/métodos , Farmacorresistência Bacteriana
11.
Respir Care ; 68(10): 1438-1448, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37221087

RESUMO

Endotracheal intubation for airway management is a common procedure in the ICU. Intubation may be difficult due to anatomic airway abnormalities but also due to physiologic derangements that predispose patients to cardiovascular collapse during the procedure. Results of studies demonstrate a high incidence of morbidity and mortality associated with airway management in the ICU. To reduce the likelihood of complications, medical teams must be well versed in the general principles of intubation and be prepared to manage physiologic derangements while securing the airway. In this review, we present relevant literature on the approach to endotracheal intubation in the ICU and provide pragmatic recommendations relevant to medical teams performing intubations in patients who are physiologically unstable.


Assuntos
Intubação Intratraqueal , Choque , Humanos , Intubação Intratraqueal/métodos , Unidades de Terapia Intensiva , Manuseio das Vias Aéreas , Incidência
12.
Lancet Reg Health Southeast Asia ; 15: 100217, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614346

RESUMO

Background: Daily oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, but no study has evaluated combination prevention interventions with PrEP for transgender women (TGW) and men who have sex with men (MSM) who sell sex. Methods: The Combination Prevention Effectiveness (COPE) study was a community-based, non-randomized implementation study in Bangkok and Pattaya, Thailand. Participants were HIV-negative MSM and TGW aged 18-26 years who reported exchanging sex with men in the prior 12 months and who met 2014 U.S. Public Health Service PrEP eligibility criteria. The intervention included quarterly HIV testing, semiannual testing for sexually transmitted infections, provision of condoms with lubricant, and the opportunity to initiate or end daily oral PrEP use at any time during study participation. Participants taking PrEP received monthly adherence counseling and short message service reminders. The primary outcome was HIV incidence rate ratio (IRR) on PrEP vs. not on PrEP. Secondary outcomes were PrEP initiation, PrEP use at 12 months, and PrEP adherence. Findings: From October 2017 to August 2019, 846 participants were enrolled: 531 (62.8%) immediately initiated PrEP; 104 (12.3%) subsequently initiated PrEP, and 211 (24.9%) never initiated PrEP. Among those initiating PrEP within 30 days of enrollment; 85.9% were on PrEP at the 12-months. When taking PrEP, participants reported adherent PrEP use at 94.2% of quarterly assessments. Ten HIV seroconversions occurred without PrEP use (incidence rate [IR] = 3.42 per 100 person-years [PY]; 95% CI = 1.64-6.30), while zero cases occurred with PrEP use (IR = 0.0 per 100PY; 95% CI = 0.0-0.62), with IRR = 0.0 (95% CI = 0.0-0.22; p < 0.001). Interpretation: Young Thai MSM and TGW who exchange sex can have high PrEP uptake, persistence and adherence, and low HIV incidence when offered in supportive community-based settings. Funding: U.S. National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention.

13.
Science ; 375(6587): 1373-1378, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35239409

RESUMO

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness. The entry of HNVs into host cells requires the attachment (G) and fusion (F) glycoproteins, which are the main targets of antibody responses. To understand viral infection and host immunity, we determined a cryo-electron microscopy structure of the NiV G homotetrameric ectodomain in complex with the nAH1.3 broadly neutralizing antibody Fab fragment. We show that a cocktail of two nonoverlapping G-specific antibodies neutralizes NiV and HeV synergistically and limits the emergence of escape mutants. Analysis of polyclonal serum antibody responses elicited by vaccination of macaques with NiV G indicates that the receptor binding head domain is immunodominant. These results pave the way for implementing multipronged therapeutic strategies against these deadly pathogens.


Assuntos
Antígenos Virais , Glicoproteínas , Vírus Nipah , Proteínas Virais , Ligação Viral , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Antígenos Virais/química , Glicoproteínas/química , Glicoproteínas/imunologia , Humanos , Vírus Nipah/genética , Vírus Nipah/imunologia , Multimerização Proteica , Proteínas Virais/química , Proteínas Virais/imunologia , Internalização do Vírus
14.
Infect Control Hosp Epidemiol ; 43(7): 892-897, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154681

RESUMO

OBJECTIVE: Hospitalized patients undergoing evaluation for pulmonary tuberculosis (TB) require airborne isolation while testing for Mycobacterium tuberculosis (MTB) to reduce risk of nosocomial transmission. GeneXpert MTB/RIF (Xpert) is more rapid and accurate than sputum smear microscopy, but it is not routinely used to 'rule out' infectious pulmonary TB among hospitalized patients in the United States. We sought to evaluate the diagnostic performance and cost-effectiveness of Xpert-based TB evaluation. METHODS: We conducted a retrospective cohort study of hospitalized adults evaluated for pulmonary TB at a large academic medical center in New York from 2010 to 2017. Using propensity score matching, we compared hospital length-of-stay among patients undergoing conventional smear-based TB evaluation to a control group with non-TB pneumonia. We performed a probabilistic cost-effectiveness analysis to compare Xpert-based versus conventional TB evaluation. RESULTS: In total 1,421 patients were evaluated for TB with airborne isolation and sputum testing; mycobacterial culture was positive for MTB in 49 (3.4%). Conventional TB evaluation was associated with an increase of 4.4 hospital days compared to propensity-matched controls. Xpert-based testing strategies dominated conventional TB evaluation with a cost savings of $5,947 (95% CI, $1,156-$12,540) and $4,445 (95% CI, $696-$9,526) per patient depending on the number of Xpert tests performed (1 vs 2, respectively) and assumptions about the reduction of length of stay achieved. CONCLUSIONS: In the evaluation of hospitalized patients for pulmonary TB, Xpert-based testing has superior diagnostic performance and is likely cost-effective compared to smear microscopy due to reduced hospital length-of-stay associated with more rapid test results.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Adulto , Análise Custo-Benefício , Humanos , Microscopia , Mycobacterium tuberculosis/genética , Estudos Retrospectivos , Rifampina , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico
15.
Ann Epidemiol ; 72: 1-8, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405344

RESUMO

PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Pessoas Transgênero , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Infecções Sexualmente Transmissíveis/epidemiologia , Tailândia/epidemiologia
16.
Cell Host Microbe ; 30(8): 1173-1185.e8, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35841889

RESUMO

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.


Assuntos
Infecções por HIV , Antígenos HLA-B , Progressão da Doença , Epitopos , Infecções por HIV/metabolismo , Antígenos HLA-B/genética , Antígenos HLA-B/metabolismo , Humanos , Células Matadoras Naturais , Fenótipo
17.
J Virol ; 84(19): 9831-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20660198

RESUMO

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. There are presently no licensed vaccines or treatment options approved for human or veterinarian use. Guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human HeV infection, but studies in nonhuman primates (NHP) have not been reported, and the development and approval of any vaccine or antiviral for human use will likely require efficacy studies in an NHP model. Here, we examined the pathogenesis of HeV in the African green monkey (AGM) following intratracheal inoculation. Exposure of AGMs to HeV produced a uniformly lethal infection, and the observed clinical signs and pathology were highly consistent with HeV-mediated disease seen in humans. Ribavirin has been used to treat patients infected with either HeV or NiV; however, its utility in improving outcome remains, at best, uncertain. We examined the antiviral effect of ribavirin in a cohort of nine AGMs before or after exposure to HeV. Ribavirin treatment delayed disease onset by 1 to 2 days, with no significant benefit for disease progression and outcome. Together our findings introduce a new disease model of acute HeV infection suitable for testing antiviral strategies and also demonstrate that, while ribavirin may have some antiviral activity against the henipaviruses, its use as an effective standalone therapy for HeV infection is questionable.


Assuntos
Antivirais/farmacologia , Vírus Hendra , Infecções por Henipavirus/tratamento farmacológico , Infecções por Henipavirus/etiologia , Ribavirina/farmacologia , Animais , Sequência de Bases , Encéfalo/patologia , Chlorocebus aethiops , Primers do DNA/genética , DNA Viral/genética , Modelos Animais de Doenças , Feminino , Vírus Hendra/genética , Vírus Hendra/patogenicidade , Vírus Hendra/fisiologia , Infecções por Henipavirus/patologia , Infecções por Henipavirus/virologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Radiografia , Replicação Viral
18.
PLoS Pathog ; 5(10): e1000642, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19888339

RESUMO

Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Infecções por Henipavirus/prevenção & controle , Vírus Nipah/patogenicidade , Doença Aguda , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Modelos Animais de Doenças , Furões , Glicoproteínas/imunologia , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/patologia , Humanos , Imuno-Histoquímica , Vírus Nipah/imunologia , RNA Viral/metabolismo , Distribuição Tecidual , Proteínas do Envelope Viral/imunologia , Carga Viral
19.
J Health Sci Med Res JHSMR ; 39(3): 251-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898941

RESUMO

Although Neisseria meningitidis (N. meningitidis) urogenital infections have been reported widely, meningococcal urethritis has not been reported previously in Thailand. A 42-year-old Thai male presented at a sexual health clinic with dysuria and urethral discharge following oral and insertive anal intercourse. N. meningitidis, serogroup C was cultured from a urethral discharge specimen and the patient was treated successfully with standard treatment for gonococcal urethritis. This case reflects a growing trend of reports describing meningococcal urethritis, likely resulting from sexual contact.

20.
Int J STD AIDS ; 32(8): 687-693, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33629883

RESUMO

INTRODUCTION: Data on HIV antiretroviral therapy (ART) initiation among key-affected populations will support reaching the UNAIDS goal to end AIDS by 2030. METHODS: We assessed ART initiation among HIV-positive participants of the Bangkok Men Who Have Sex with Men (MSM) Cohort Study, which enrolled sexually experienced MSM aged ≥ 18 years and included visits every four months for a period of 3-5 years, from 2006-2016. At each visit, participants had HIV testing and completed computer-assisted self-interviewing on demographics and HIV risk behaviors. If they acquired HIV infection during the study, they received active referral for HIV treatment, continued in the cohort, and were asked about ART initiation. We used logistic regression to determine factors associated with ART initiation. RESULTS: Overall, 632 (36.2%) participants were diagnosed with HIV infection; 463 (73%) had a follow-up visit reporting information about ART, of those 346 (74%) reported ART initiation, with 323 (93%) on ART initiating ART through their registered national health benefit program. Only 70 (11%) were eligible for ART at time of diagnosis, and 52 (74%) initiated ART, on average, within six months of diagnosis. Multivariable analysis evaluating factors associated with ART initiation demonstrated that low CD4 cell count at time of diagnosis was the only independent factor associated with ART initiation. CONCLUSIONS: Most HIV-positive participants in the cohort reported ART initiation through the national health benefit program but limited data suggests there could be improvements in length of time to initiation of ART. Efforts should focus on ART start in MSM and transgender women soon after HIV diagnosis.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Tailândia
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