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1.
PLoS One ; 15(6): e0234646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530972

RESUMO

BACKGROUND: Patients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert® MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures. METHODS: PLHIV attending one of the 22 participating HIV clinics, who screened positive for ≥1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment. RESULTS: Among 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated 'no MTB'. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher's exact test p = 1.00. CONCLUSIONS: While the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential.


Assuntos
Algoritmos , Antituberculosos/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/microbiologia , Micobactérias não Tuberculosas/fisiologia , Tuberculose/tratamento farmacológico , Adulto , Botsuana , Feminino , Humanos , Masculino , Micobactérias não Tuberculosas/isolamento & purificação , Fatores de Risco , Especificidade da Espécie , Resultado do Tratamento
3.
Am J Trop Med Hyg ; 103(1): 214-220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32431282

RESUMO

Country-specific interventions targeting high-risk groups are necessary for a global reduction in Tuberculosis (TB)/HIV burden. We analyzed the data of 13,802 TB cases diagnosed in Harare, Zimbabwe, during 2013-2017. Pearson's chi-square tests and multivariate logistic regression models were used to identify patient characteristics significantly associated with TB/HIV coinfection. Of the 13,802 TB cases analyzed, 9,725 (70.5%) were HIV positive. A significantly higher odds of having TB/HIV coinfection diagnosis was found among females, patients aged 25-64 years, previously treated cases, and acid-fast bacillus sputum smear-negative cases. Compared with nondisseminated pulmonary TB, miliary TB (adjusted odds ratio [aOR]: 1.469, 95% CI: 1.071, 2.015) and TB meningitis (aOR: 1.715, 95% CI: 1.074, 2.736) both had a significantly higher odds for TB/HIV coinfection, whereas pleural TB (aOR 0.420, 95% CI: 0.354, 0.497) and all other extrapulmonary TB (EPTB) (aOR: 0.606, 95% CI: 0.516 0.712) were significantly less likely to have TB/HIV coinfection. The risk for TB/HIV coinfection varied significantly by patients' sociodemographic and clinical characteristics in Harare. Our finding that different forms of EPTB have different relationships with HIV coinfection has extended the knowledge base about clinical markers for TB/HIV coinfection which can lead to a greater public health impact on eliminating TB/HIV infection.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Tuberculose Pulmonar/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/virologia , Adulto Jovem , Zimbábue/epidemiologia
4.
BMC Infect Dis ; 20(1): 325, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380957

RESUMO

BACKGROUND: Tuberculosis (TB) and HV have been intertwined and makeup a deadly human syndemic worldwide, especially in developing countries like Ethiopia. Previous studies have reported different TB incidences and its association with CD4+ T cell counts among HIV positive patients in Ethiopia. Thus, the goal of this meta-analysis was, first, to determine pooled incident TB among adult HIV positive patients, and second, to assess the association between incident TB and baseline CD4+ T cell count strata's. METHODS: We searched PubMed, Cochrane library, Science Direct and Google scholar databases from June 1 to 30, 2018. The I2 statistics and Egger's regression test was used to determine heterogeneity and publication bias among included studies respectively. A random effects model was used to estimate pooled incident TB and odds ratio with the respective 95% confidence intervals using Stata version 11.0 statistical software. RESULTS: A total of 403 research articles were identified, and 10 studies were included in the meta-analysis. The pooled incident TB among adult HIV infected patients in Ethiopia was 16.58% (95% CI; 13.25-19.91%). Specifically, TB incidence in Pre-ART and ART was 17.16% (95% CI; 7.95-26.37%) and 16.24% (95% CI; 12.63-19.84%) respectively. Moreover, incident TB among ART receiving patients with baseline CD4+ T cell count < and > 200 cells/mm3 was 28.86% (95% CI; 18.73-38.98%) and 13.7% (95% CI; 1.41-25.98%) correspondingly. The odds of getting incident TB was 2.88 (95% CI; 1.55-5.35%) for patients with baseline CD4+ T cell count < 200 cells/mm3 compared to patients with baseline CD4+ T cell count > 200 cells/mm3. CONCLUSION: High incident TB among adult HIV positive patients was estimated, especially in patients with CD4+ T cell count < 200 cells/mm3. Therefore, Early HIV screening and ART initiation, as well as strict compliance with ART and increasing the coverage of TB preventive therapy to more risky groups are important to prevent the problem. TRIAL REGISTRATION: Study protocol registration: CRD42018090802.


Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/microbiologia , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Adulto , Etiópia/epidemiologia , Infecções por HIV/epidemiologia , Soropositividade para HIV/complicações , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/microbiologia , Humanos , Incidência , Pessoa de Meia-Idade , Razão de Chances , Cooperação do Paciente , Fatores de Risco , Tuberculose/patologia , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 254, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228480

RESUMO

BACKGROUND: To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. METHODS: From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. RESULTS: Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.


Assuntos
Infecções por HIV/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mucosa Nasal/microbiologia , Infecções Estafilocócicas/epidemiologia , Adulto , Antibacterianos/farmacologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Abuso de Substâncias por Via Intravenosa/complicações , Taiwan/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia
6.
PLoS One ; 15(4): e0231637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315335

RESUMO

INTRODUCTION: The contribution of high tuberculosis (TB) transmission pockets in propagating area-wide transmission has not been adequately described in Zimbabwe. This study aimed to describe the presence of hotspot transmission of TB cases in Harare city from 2011 to 2012 using geospatial techniques. METHODS: Anonymised TB patient data stored in an electronic database at Harare City Health department was analysed using geospatial methods. Confirmed TB cases were mapped using geographic information system (GIS). Global Moran's I and Anselin Local Moran's I (LISA) were used to assess clustering and the local Getis-Ord Gi* was used to estimate hotspot phenomenon of TB cases in Harare City for the period between 2011 and 2012. RESULTS: A total of 12,702 TB cases were accessed and mapped on the Harare City map. In both 2011 and 2012, ninety (90%) of cases were new and had a high human immunodeficiency virus (HIV)/TB co-infection rate of 72% across all suburbs. Tuberculosis prevalence was highest in the Southern district in both 2011 and 2012. There were pockets of spatial distribution of TB prevalence across West South West, Southern, Western, South Western and Eastern health districts. TB hot spot occurrence was restricted to the West South West, parts of South Western, Western health districts. West South West district had an increased peri-urban population with inadequate social services including health facilities. These conditions were conducive for increased intensity of TB occurrence, a probable indication of high transmission especially in the presence of high HIV co-infection. CONCLUSIONS AND RECOMMENDATIONS: Increased TB transmission was limited to a health district with high informal internal migrants with limited health services in Harare City. To minimise spread of TB into greater Harare, there is need to improve access to TB services in the peri-urban areas.


Assuntos
Transmissão de Doença Infecciosa , Infecções por HIV/epidemiologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sistemas de Informação Geográfica , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise Espacial , Tuberculose/complicações , Tuberculose/microbiologia , Tuberculose/virologia , População Urbana , Adulto Jovem , Zimbábue/epidemiologia
7.
PLoS One ; 15(3): e0229875, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130279

RESUMO

BACKGROUND: In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS: We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS: We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/µl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p <0.001]. CONCLUSIONS: Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/virologia , Adulto , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Estudos Prospectivos , Fatores de Risco , População Rural , Tanzânia/epidemiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia
8.
PLoS Pathog ; 16(3): e1008333, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32119719

RESUMO

Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1-3 days post-infection (dpi)), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic SIV infection (46-55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the GI tract and peripheral lymph nodes. Tissue viral loads, plasma cytokines and plasma markers of gut dysfunction were also measured throughout the course of early infection. While a strong, but transient, interferon-based inflammatory response was observed, the levels of plasma markers linked to enteropathy did not increase. Accordingly, no significant increases in apoptosis of either mucosal enterocytes or lymphocytes, and no damage to the mucosal epithelium were documented during early SIVsab infection of AGMs. These findings were supported by RNAseq of the gut tissue, which found no significant alterations in gene expression that would indicate microbial translocation. Thus, for the first time, we confirmed that gut epithelial integrity is preserved, with no evidence of microbial translocation, in AGMs throughout early SIVsab infection. This might protect AGMs from developing intestinal dysfunction and the subsequent chronic inflammation that drives both HIV disease progression and HIV-associated comorbidities.


Assuntos
Mucosa Intestinal/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Translocação Bacteriana , Chlorocebus aethiops , Progressão da Doença , Microbioma Gastrointestinal , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Mucosa Intestinal/microbiologia , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/microbiologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia
9.
BMC Infect Dis ; 20(1): 229, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188399

RESUMO

BACKGROUND: The detection of Mycobacterium tuberculosis (MTB) in the intensive care unit (ICU) presents several challenges, mainly associated to the clinical state of the patient. The presence of HIV infection further aggravates this scenario, requiring a reliable collection method, with better performance in the microbiological/molecular techniques to be used. We evaluated the performance of two methods for sample collection, mini bronchoalveolar lavage (Mini-BAL) and endotracheal aspirate (ETA), for diagnosis of pulmonary tuberculosis (PTB) in critically ill patients. METHODS: This prospective study involved 26 HIV positive ICU internalized patients, with presumptive PTB who required mechanical ventilation. Two samples were obtained prospectively from 26 HIV ICU patients with presumptive PTB by Mini-BAL and ETA. The samples were processed for smear microscopy, Löwenstein-Jensen medium and the BACTEC Mycobacteria Growth Indicator Tube 960 system®. We define as confirmed PTB patients with positive MTB culture. Furthermore, all samples obtained through the Mini-BAL were analyzed by Xpert® MTB/RIF. RESULTS: Our results demonstrated that the respiratory samples obtained by Mini-BAL were able to increase MTB detection in critically ill patients with presumptive PTB. The Mini-BAL allowed 30% increased recovery and guaranteed enough sample volume for processing in all methods. In addition, the larger volume of the samples obtained with this technique enabled the Xpert® MTB/RIF molecular test for diagnosis of TB. CONCLUSIONS: The Mini-BAL showed be an acceptable alternative to ETA in this population, since these critically ill and often-immunocompromised patients are more likely to develop complications related to invasive procedures.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Manejo de Espécimes/métodos , Tuberculose Pulmonar/diagnóstico , Adulto , Estado Terminal , Feminino , Infecções por HIV/microbiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Estudos Prospectivos , Respiração Artificial , Tuberculose Pulmonar/microbiologia
10.
J Womens Health (Larchmt) ; 29(3): 362-375, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32109181

RESUMO

Background: Advancements in next-generation sequencing have allowed for a more complete understanding of the vaginal microbiome and its role in health and disease. The role of race/ethnicity in the composition of the vaginal microbiome and what is deemed normal/healthy microbiome is conflicting. Thus, the purpose of this review is to synthesize research that investigated the vaginal microbiome in Black women in the United States by using advanced 16S analysis. Methods: Searches of Pubmed, Google Scholar, and relevant journals for publications between January 2008 and July 2018 were conducted. Eligibility criteria were that the study: (1) used a molecular technique for sequencing of the vaginal microbiome, (2) reported the microbiome by race/ethnicity that included Black women, and (3) was conducted in the United States. Results: Our review selected 18 manuscripts that met the inclusion criteria for full review. Three themes emerged: the vaginal microbiome in healthy women versus women with bacterial vaginosis (BV); vaginal microbiome considerations in HIV; and vaginal microbiome considerations in preterm labor/birth. Overall, our review found that a majority of Black women (including HIV-positive women) have a Lactobacillus dominant group. Specifically, Lactobacillus iners was the most frequently reported Lactobacillus species. Non-Lactobacillus dominant groups were also reported to be found in healthy asymptomatic Black women. The vaginal microbiome's influence on preterm labor and/or birth among Black women was inconclusive and warrants further investigation. Conclusions: The role that the microbiome plays in health and disease among Black women warrants further research to better elucidate the definition of a healthy versus pathogenic microbiome. The wide variability in methods for BV diagnostics and defining preterm labor/birth are significant limitations that should be considered when conducting comparative studies.


Assuntos
Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Microbiota/fisiologia , Vagina/microbiologia , Afro-Americanos/estatística & dados numéricos , Feminino , Infecções por HIV/microbiologia , Humanos , Lactobacillus/isolamento & purificação , Gravidez , Nascimento Prematuro/microbiologia , Estados Unidos , Vaginose Bacteriana/microbiologia
11.
Cell Mol Life Sci ; 77(14): 2751-2769, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32002588

RESUMO

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.


Assuntos
Aterosclerose/genética , Infecções Bacterianas/genética , Infecções por HIV/genética , Receptores Toll-Like/genética , Aterosclerose/complicações , Aterosclerose/microbiologia , Aterosclerose/virologia , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Chlamydophila pneumoniae/patogenicidade , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Helicobacter pylori/patogenicidade , Humanos , Porphyromonas gingivalis/patogenicidade
12.
Lancet Respir Med ; 8(4): 368-382, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32066534

RESUMO

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is a new test for tuberculosis undergoing global roll-out. We assessed the performance of Ultra compared with Xpert MTB/RIF (Xpert) in an HIV-endemic setting where previous tuberculosis is frequent and current test performance is suboptimal. METHODS: In this two-cohort diagnostic accuracy study, we used sputum samples from patients in South Africa to evaluate the accuracy of Ultra and Xpert against a single culture reference standard. For the first cohort (cohort A), we recruited adults (aged ≥18 years) with symptoms of presumptive tuberculosis at Scottsdene clinic in Cape Town, South Africa. We collected three sputum samples from each patient in cohort A, two at the first visit of which one was tested using Xpert and the other was tested using culture, and one sample the next morning which was tested using Ultra. In a separate cohort of patients with presumptive tuberculosis and recent previous tuberculosis (≤2 years) who had submitted sputum samples to the National Health Laboratory Services (cohort B), decontaminated sediments were, after processing, randomly allocated (1:1) for testing with Ultra or Xpert. For both cohorts we calculated the sensitivity and specificity of Ultra and Xpert and evaluated the effects of different methods of interpreting Ultra trace results. FINDINGS: Between Feb 6, 2016, and Feb 2, 2018, we recruited 302 people into cohort A, all of whom provided sputum samples and 239 were included in the head-to-head analyses of Ultra and Xpert. For cohort B, we collected sputum samples from eligible patients who had submitted samples between Dec 6, 2016, and Dec 21, 2017, to give a cohort of 831 samples, of which 352 were eligible for inclusion in analyses and randomly assigned to Ultra (n=173) or Xpert (n=179). In cohort A, Ultra gave more non-actionable results (not positive or negative) than did Xpert (28 [10%] 275 vs 14 [5%] 301; p=0·011). In the head-to-head analysis, in smear-negative patients, sensitivity of Ultra was 80% (95% CI 64-90) and of Xpert was 73% (57-85; p=0·45). Overall, specificity of Ultra was lower than that of Xpert (90% [84-94] vs 99% [95-100]; p=0·001). In cohort B, overall sensitivity was 92% (81-98) for Xpert versus 86% (73-95; p=0·36) for Ultra and overall specificity was 69% (60-77) for Ultra versus 84% (78-91; p=0·005) for Xpert. Ultra specificity estimates improved after reclassification of results with the lowest Ultra-positive semiquantitation category (trace) to negative (15% [8-22]). In cohort A, the positive predictive value (PPV) for Ultra was 78% (67-87) and for Xpert was 96% (87-99; p=0·004); in cohort B, the PPV for Ultra was 50% (43-57) and for Xpert was 70% (61-78; p=0·014). Ultra PPV estimates in previously treated patients were low: at 15% tuberculosis prevalence, half of Ultra-positive patients with presumptive tuberculosis would be culture negative, increasing to approximately 70% in patients with recent previous tuberculosis. In cohort B, 21 (28%) of 76 samples that were Ultra positive were rifampicin indeterminate (all trace) and, like cohort A, most were culture negative (19 [90%] of 21). INTERPRETATION: In a setting with a high burden of previous tuberculosis, Ultra generated more non-actionable results and had diminished specificity compared with Xpert. In patients with recent previous tuberculosis, a quarter of Ultra-positive samples were indeterminate for rifampicin resistance and culture negative, suggesting that additional drug-resistance testing will probably be unsuccessful. Our data have implications for the handling of Ultra-positive results in patients with previous tuberculosis in high burden settings. FUNDING: South African Medical Research Council, the EDCTP2 program, and the Faculty of Medicine and Health Sciences, Stellenbosch University.


Assuntos
Técnicas Bacteriológicas/métodos , Mycobacterium tuberculosis/classificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória , Recidiva , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , África do Sul/epidemiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
13.
Lancet Infect Dis ; 20(5): 607-617, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32085847

RESUMO

BACKGROUND: Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding. METHODS: We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis. FINDINGS: Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks. INTERPRETATION: Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities. FUNDING: Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. VIDEO ABSTRACT.


Assuntos
Máscaras/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/virologia , Testes Diagnósticos de Rotina/métodos , Feminino , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , África do Sul , Escarro/microbiologia , Escarro/virologia , Adulto Jovem
14.
Dig Dis Sci ; 65(3): 800-817, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32030625

RESUMO

Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIV-related intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Infecções por HIV/microbiologia , Homossexualidade Masculina , Comportamento Sexual/fisiologia , Disbiose/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino
15.
PLoS Pathog ; 16(2): e1008240, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106253

RESUMO

Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen is particularly relevant in HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis is the ability of the fungus to survive and replicate within the phagosome of macrophages, as well as its ability to be expelled from host cells via a novel non-lytic mechanism known as vomocytosis. Here we show that cryptococcal vomocytosis from macrophages is strongly enhanced by viral coinfection, without altering phagocytosis or intracellular proliferation of the fungus. This effect occurs with distinct, unrelated human viral pathogens and is recapitulated when macrophages are stimulated with the anti-viral cytokines interferon alpha or beta (IFNα or IFNß). Importantly, the effect is abrogated when type-I interferon signalling is blocked, thus underscoring the importance of type-I interferons in this phenomenon. Lastly, our data help resolve previous, contradictory animal studies on the impact of type I interferons on cryptococcal pathogenesis and suggest that secondary viral stimuli may alter patterns of cryptococcal dissemination in the host.


Assuntos
Coinfecção , Criptococose , Cryptococcus neoformans , Infecções por HIV , HIV-1 , Macrófagos , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/patologia , Coinfecção/virologia , Criptococose/imunologia , Criptococose/microbiologia , Criptococose/patologia , Criptococose/virologia , Cryptococcus neoformans/imunologia , Cryptococcus neoformans/patogenicidade , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Interferon-alfa/imunologia , Interferon beta/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/virologia , Transdução de Sinais/imunologia
16.
BMC Infect Dis ; 20(1): 141, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059703

RESUMO

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.


Assuntos
Antígenos de Fungos/sangue , Criptococose/epidemiologia , Infecções por HIV/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Antifúngicos/uso terapêutico , Estudos Transversais , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/mortalidade , Cryptococcus , Feminino , Fluconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Serra Leoa/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos
17.
Infection ; 48(2): 259-265, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31993971

RESUMO

BACKGROUND: Rectal sexually transmitted infections (STI) are common in men having sex with men (MSM). Mycoplasma genitalium is increasingly being reported in this localization, but due to frequent lack of symptoms at this site, clinical significance is still unclear. Rectal prevalence of Mycoplasma hominis and Ureaplasma species is not well studied so far. We aimed to investigate the prevalence and antibiotic sensitivity of rectal Mollicutes in our HIV-cohort. METHODS: In 227 MSM presenting for annual STI-screening, 317 anorectal swabs were collected from January 2017 to December 2018. PCR was performed for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, M. genitalium and also culture for M. hominis and Ureaplasma spec. RESULTS: Prevalence for M. genitalium, M. hominis, Ureaplasma spec., C. trachomatis and N. gonorrhoeae was 8.2%, 7.3%, 12.0%, 5.1% and 1.9%, respectively. Patients were asymptomatic with few exceptions. Seroprevalence of syphilis in 227 MSM was 41.9%. In 20 strains of M. genitalium, resistance-associated mutations to macrolides and quinolones were found in 60% and 30%, respectively; in five strains (25%) to both. M. hominis and Ureaplasma spec. frequently occurred combined, mostly in significant quantity consistent with infection. M. hominis and Ureaplasma spec. regularly showed sensitivity to tetracycline. CONCLUSION: At screening, rectal colonization with Mollicutes was common in our patients, but rarely caused symptoms. Due to rising antibiotic resistance of M. genitalium against quinolones, therapeutic options are increasingly limited. Treatment should be guided by antibiotic resistance testing including quinolones. In persisting anorectal symptoms, M. hominis and Ureaplasma spec. should also be taken into account.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas , Infecções por HIV/complicações , Doenças Retais/microbiologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Tenericutes/efeitos dos fármacos , Adulto , Alemanha/epidemiologia , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Doenças Retais/complicações , Doenças Retais/epidemiologia , Tenericutes/isolamento & purificação , Tenericutes/fisiologia
18.
PLoS Pathog ; 16(1): e1008114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31951641

RESUMO

Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is necessary for the development of Kaposi's sarcoma (KS), which most often develops in HIV-infected individuals. KS frequently has oral manifestations and KSHV DNA can be detected in oral cells. Numerous types of cancer are associated with the alteration of microbiome including bacteria and virus. We hypothesize that oral bacterial microbiota affects or is affected by oral KS and the presence of oral cell-associated KSHV DNA. In this study, oral and blood specimens were collected from a cohort of HIV/KSHV-coinfected individuals all previously diagnosed with KS, and were classified as having oral KS with any oral cell-associated KSHV DNA status (O-KS, n = 9), no oral KS but with oral cell-associated KSHV DNA (O-KSHV, n = 10), or with neither oral KS nor oral cell-associated KSHV DNA (No KSHV, n = 10). We sequenced the hypervariable V1-V2 region of the 16S rRNA gene present in oral cell-associated DNA by next generation sequencing. The diversity, richness, relative abundance of operational taxonomic units (OTUs) and taxonomic composition of oral microbiota were analyzed and compared across the 3 studied groups. We found impoverishment of oral microbial diversity and enrichment of specific microbiota in O-KS individuals compared to O-KSHV or No KSHV individuals. These results suggest that HIV/KSHV coinfection and oral microbiota might impact one another and influence the development of oral KS.


Assuntos
Bactérias/isolamento & purificação , DNA Viral/genética , Infecções por HIV/microbiologia , Herpesvirus Humano 8/genética , Microbiota , Boca/microbiologia , Sarcoma de Kaposi/virologia , Bactérias/classificação , Bactérias/genética , Estudos de Coortes , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/virologia , Estudos Transversais , DNA Viral/metabolismo , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Herpesvirus Humano 8/isolamento & purificação , Herpesvirus Humano 8/fisiologia , Humanos , Boca/virologia , Filogenia , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/microbiologia
20.
Am J Respir Crit Care Med ; 201(4): 445-457, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31682463

RESUMO

Rationale: Mechanisms of HIV-associated chronic obstructive pulmonary disease (COPD) are poorly understood. The oral microbiome shapes the lung microbiome, and gut dysbiosis can affect lung diseases; however, relationships of the oral and gut microbiome to COPD in HIV have not been explored.Objectives: To examine alterations in the oral and gut microbiome associated with pulmonary disease in persons with HIV (PWH).Methods: Seventy-five PWH and 93 HIV-uninfected men from the MACS (Multicenter AIDS Cohort Study) performed pulmonary function testing. Sequencing of bacterial 16S ribosomal RNA in saliva and stool was performed. We used nonmetric multidimensional scaling, permutational multivariate ANOVA, and linear discriminant analysis to analyze communities by HIV and lung function.Measurements and Main Results: Oral microbiome composition differed by HIV and smoking status. Alterations of oral microbial communities were observed in PWH with abnormal lung function with increases in relative abundance of Veillonella, Streptococcus, and Lactobacillus. There were no significant associations between the oral microbiome and lung function in HIV-uninfected individuals. No associations with HIV status or lung function were seen with the gut microbiome.Conclusions: Alterations of oral microbiota in PWH were related to impaired pulmonary function and to systemic inflammation. These results suggest that the oral microbiome may serve as a biomarker of lung function in HIV and that its disruption may contribute to COPD pathogenesis.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Microbiota , Boca/microbiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
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