RESUMO
Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma--caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.
Assuntos
Antígenos de Fungos , Infecções por HIV , Histoplasma , Histoplasmose , Humanos , Histoplasmose/epidemiologia , Histoplasmose/urina , Histoplasmose/diagnóstico , Histoplasma/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Prevalência , Antígenos de Fungos/urina , Antígenos de Fungos/imunologia , América Latina/epidemiologia , África/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/urinaRESUMO
Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions.
Assuntos
Infecções por HIV , Histoplasma , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Masculino , Feminino , Adulto , Suriname , Histoplasma/isolamento & purificação , Infecções por HIV/complicações , Pessoa de Meia-Idade , Antígenos de Fungos/urina , Sensibilidade e Especificidade , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/urina , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Imunoensaio/métodosRESUMO
Talaromyces marneffei is a fungal opportunistic infection usually seen in immunocompromised patients from eastern countries. In the US when examining HIV-patients for suspected fungal infections, laboratory serological tests guide therapy until cultures are available. We present the case of a 35-year-old HIV patient originally from Thailand in which urine lab results were positive for Blastomyces and Histoplasma antigen, but biopsy showed T. marneffei. Concomitantly the patient presented with hyponatremia which was deemed to be from SIADH. We present the first case of a patient with T. marneffei cross reactivity with Blastomyces, Histoplasma and SIADH due to pulmonary disease.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antígenos de Fungos/urina , Blastomyces/imunologia , Histoplasma/imunologia , Micoses/diagnóstico , Talaromyces/imunologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Adulto , Blastomyces/isolamento & purificação , Reações Cruzadas , Histoplasma/isolamento & purificação , Humanos , Masculino , Micoses/imunologia , Micoses/microbiologia , Micoses/urina , Testes Sorológicos , Talaromyces/isolamento & purificação , TailândiaRESUMO
BACKGROUND: The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings. METHODS AND FINDINGS: A cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30-43), 45.4% were female, median CD4 cell count at admission was 76 cells/µl (IQR 23-206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%-55.2%) mortality risk in the high-risk group compared to 12.5% (95% CI 5.7%-25.4%) in the low-risk group (p < 0.001). The odds ratio (OR) for mortality was 6.1 (95% CI 2.4-15.2) in high-risk patients compared to low-risk patients (p < 0.001). Discrimination (c-statistic 0.70, 95% CI 0.63-0.76) and calibration (Hosmer-Lemeshow statistic, p = 0.78) were good in the derivation cohort, and similar in the external validation cohort (complete cases n = 372, c-statistic 0.68 [95% CI 0.61-0.74]). The validation cohort included 644 patients between January 2013 and August 2015. Median age was 36 years, 48.9% were female, and median CD4 count at admission was 61 (IQR 21-145). OR for mortality was 5.3 (95% CI 2.2-9.5) for high compared to low-risk patients (complete cases n = 372, p < 0.001). The score also predicted patients at higher risk of death both pre- and post-discharge. A simplified score (any 3 or more of the predictors) performed equally well. The main limitations of the scores were their imperfect accuracy, the need for access to urine LAM testing, modest study size, and not measuring all potential predictors of mortality (e.g., tuberculosis drug resistance). CONCLUSIONS: This risk score is capable of identifying patients who could benefit from enhanced clinical care, follow-up, and/or adjunctive interventions, although further prospective validation studies are necessary. Given the scale of HIV/TB morbidity and mortality in African hospitals, better prognostic tools along with interventions could contribute towards global targets to reduce tuberculosis mortality.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Lipopolissacarídeos/urina , Tuberculose/diagnóstico , Tuberculose/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/urina , Adulto , África Subsaariana/epidemiologia , Estudos de Coortes , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/urina , Hospitalização , Humanos , Pacientes Internados , Masculino , Programas de Rastreamento/métodos , Prognóstico , Projetos de Pesquisa , Fatores de Risco , Análise de Sobrevida , Tuberculose/urina , UrináliseRESUMO
BACKGROUND: The urine lipoarabinomannan (LAM) lateral flow assay is a point-of-care test to diagnose HIV-associated tuberculosis (TB). We assessed the performance of urine LAM in HIV-positive patients presenting to the emergency center and evaluated the interobserver agreement between emergency center physicians and laboratory technologists. SETTING: A cross-sectional diagnostic study was performed at the emergency center of a district hospital in a high HIV-prevalence community in South Africa. METHODS: Consecutive HIV-positive adults presenting with ≥1 WHO TB symptom were enrolled over a 16-month period. A urine LAM test was performed at point-of-care by an emergency physician and interpreted independently by 2 physicians. A second test was performed in the laboratory and interpreted independently by 2 laboratory technologists. The reference standard was a positive TB culture or Xpert MTB/RIF test on sputum or appropriate extrapulmonary samples. We compared diagnostic accuracy and reproducibility of urine LAM between point-of-care readers and laboratory readers. RESULTS: One thousand three hundred eighty-eight samples (median, 3 samples/participant) were sent for TB microbiology tests in 411 participants; 170 had confirmed TB (41.4%). Point-of-care and laboratory-performed urine LAM had similar sensitivity (41.8% vs 42.0%, P = 1.0) and specificity (90.5% vs 87.5%, P = 0.23). Moderate agreement was found between point-of-care and laboratory testing (κ = 0.62), but there was strong agreement between point-of-care readers (κ = 0.95) and between laboratory readers (κ = 0.94). Positive percent agreement between point-of-care and laboratory readers was 68% and negative percent agreement 92%. CONCLUSION: There is no diagnostic accuracy advantage in laboratory-performed versus point-of-care-performed urine LAM tests in emergency care centers in high-burden settings.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/urina , Serviço Hospitalar de Emergência , Lipopolissacarídeos/urina , Tuberculose Pulmonar/urina , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , Estudos Transversais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Testes Imediatos , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/etiologiaRESUMO
BACKGROUND: Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374â000 annual HIV-positive deaths globally. Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes. METHODS: We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa. We included HIV-positive medical inpatients aged 18 years or more who were not taking tuberculosis treatment. We randomly assigned patients (1:1), using a computer-generated list of random block size stratified by site, to either the standard-of-care or the intervention screening group, irrespective of symptoms or clinical presentation. Attending clinicians made decisions about care; and patients, clinicians, and the study team were masked to the group allocation. In both groups, sputum was tested using the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA). In the standard-of-care group, urine samples were not tested for tuberculosis. In the intervention group, urine was tested with the Alere Determine TB-LAM Ag (TB-LAM; Alere, Waltham, MA, USA), and Xpert assays. The primary outcome was all-cause 56-day mortality. Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count, haemoglobin, clinical suspicion for tuberculosis; and by study site and calendar time. We used an intention-to-treat principle for our analyses. This trial is registered with the ISRCTN registry, number ISRCTN71603869. FINDINGS: Between Oct 26, 2015, and Sept 19, 2017, we screened 4788 HIV-positive adults, of which 2600 (54%) were randomly assigned to the study groups (n=1300 for each group). 13 patients were excluded after randomisation from analysis in each group, leaving 2574 in the final intention-to-treat analysis (n=1287 in each group). At admission, 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per µL (IQR 79-436). Mortality at 56 days was reported for 272 (21%) of 1287 patients in the standard-of-care group and 235 (18%) of 1287 in the intervention group (adjusted risk reduction [aRD] -2·8%, 95% CI -5·8 to 0·3; p=0·074). In three of the 12 prespecified, but underpowered subgroups, mortality was lower in the intervention group than in the standard-of-care group for CD4 counts less than 100 cells per µL (aRD -7·1%, 95% CI -13·7 to -0·4; p=0.036), severe anaemia (-9·0%, -16·6 to -1·3; p=0·021), and patients with clinically suspected tuberculosis (-5·7%, -10·9 to -0·5; p=0·033); with no difference by site or calendar period. Adverse events were similar in both groups. INTERPRETATION: Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive inpatients, but might benefit some high-risk subgroups. Implementation could contribute towards global targets to reduce tuberculosis mortality. FUNDING: Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, and the Wellcome Trust.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/urina , Países em Desenvolvimento , Soropositividade para HIV/urina , Programas de Rastreamento , Tuberculose/urina , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Método Duplo-Cego , Farmacorresistência Bacteriana , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/mortalidade , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Rifampina/uso terapêutico , África do Sul , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade , UrináliseAssuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Medula Óssea/microbiologia , Fungemia/microbiologia , HIV/isolamento & purificação , Histoplasma/isolamento & purificação , Histoplasmose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/urina , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/urina , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Antirretrovirais/administração & dosagem , Antirretrovirais/farmacologia , Histoplasma/efeitos dos fármacos , Histoplasmose/tratamento farmacológico , Histoplasmose/urina , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Masculino , Carga ViralRESUMO
BACKGROUND: Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. METHODS: Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. RESULTS: 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. CONCLUSION: This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.
Assuntos
Infecções por HIV/microbiologia , Lipopolissacarídeos/urina , Tuberculose/urina , Urinálise/métodos , Coleta de Urina/métodos , Infecções Oportunistas Relacionadas com a AIDS/urina , Adulto , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/diagnósticoAssuntos
Antígenos de Fungos/urina , Criptococose/diagnóstico , Criptococose/urina , Cryptococcus neoformans/metabolismo , Temperatura Alta , Urinálise/métodos , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/urina , Antígenos de Fungos/imunologia , Criptococose/complicações , Infecções por HIV/complicações , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: HIV-associated tuberculosis (TB) co-infection remains an enormous burden to international public health. Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB. Determine TB-LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission. However, it remains unclear if this approach can impact clinical outcomes. The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current, sputum-based screening. METHODS: The trial is a pragmatic, individually randomised, multi-country (Malawi and South Africa) clinical trial with two study arms (1:1 recruitment). Unselected HIV-positive patients admitted to medical wards, irrespective of presentation, meeting the inclusion criteria and giving consent will be randomized to screening for TB using either: (i) 'standard of care'- testing of sputum using the Xpert MTB/RIF assay (Xpert) or (ii) 'intervention'- testing of sputum using Xpert and testing of urine using (a) Determine TB-LAM lateral-flow assay and (b) Xpert following concentration of urine by centrifugation. Patients will be excluded if they have received TB treatment in the previous 12 months, if they have received isoniazid preventive therapy in the last 6 months, if they are aged <18 years or they live outside the pre-specified geographical area. Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment. Both the study and routine medical team will be masked to study arm allocation. 1300 patients will be enrolled per arm (equal numbers at the two trial sites). The primary endpoint is all-cause mortality at 56 days. An economic analysis will be conducted to project long-term outcomes for shorter-term trial data, including cost-effectiveness. DISCUSSION: This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB, which could feasibly be scaled up in high-burden settings if shown to be efficacious and cost-effective. We discuss the challenges of designing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes. We also elaborate on the practical and ethical issues of 'testing a test' in general. TRIAL REGISTRATION: ISRCTN Registry ( ISRCTN71603869 ) prospectively registered 08 May 2015; the South African National Controlled Trials Registry (DOH-27-1015-5185) prospectively registered October 2015.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/urina , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tuberculose/urina , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Síndrome da Imunodeficiência Adquirida/microbiologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Infecções por HIV/microbiologia , Hospitalização , Humanos , Isoniazida/uso terapêutico , Malaui , Programas de Rastreamento , África do Sul , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Urinálise/métodosRESUMO
Abstract JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215 bp) and IG (610 bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4+/TCD8+ lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Vírus JC/genética , DNA Viral/urina , Reação em Cadeia da Polimerase , Estudos Transversais , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/urina , Vírus JC/isolamento & purificação , Contagem de Linfócito CD4 , Carga Viral , Coinfecção/virologiaRESUMO
JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/urina , Adolescente , Adulto , Brasil , Contagem de Linfócito CD4 , Criança , Coinfecção/virologia , Estudos Transversais , DNA Viral/urina , Feminino , Humanos , Vírus JC/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Carga Viral , Adulto JovemRESUMO
We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Lipopolissacarídeos/urina , Tuberculose/epidemiologia , Tuberculose/urina , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Países em Desenvolvimento , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Incidência , Lipopolissacarídeos/análise , Masculino , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Escarro/microbiologia , Tanzânia/epidemiologia , Tuberculose/diagnóstico , Urinálise/métodosRESUMO
BACKGROUND: Human Cytomegalovirus (HCMIV infects humans in all geographic areas. Polymorphisms ofglycoprotein B (gB) have been usedforgenotypic characterization of HCMV However information of gB genotyping of HCMV in Thailand is not clearly known especially in children. MATERIAL AND METHOD: A cross-sectional study was conducted to assess HCMV infection in 236 HIV seronegative and HIV seropositive children who attended an orphanage in Nonthaburi, Thailand by nested-PCR technique using urine specimens. HCMV gB genotypes were determined by restrictionfragment length polymorphism (RFLP), andDNA sequencing technique. RESULTS: Sixty-one percent (144/236) of the samples were HCMV positive, which consisted of 66.1% (37/56) of the HIV seropositive children and 59.4% (107/180) of the HIVsero-negative children. Multivariate analysis showed that children who living in one particular room were independently associated with HCMVinfection. Genotypic analysis revealed that the most prevalent genotype in these children was gB1; 85.4% (111/130) followed by gB3; 4.6% (6/130), gB2 and gB4 each at 2.3% (3/130). Mixed gB genotypes were identified in 5.4% (7/130) of the samples. CONCLUSION: HCMV infection, in particular gB1 genotype was commonly ident fled among these Thai orphans. Living in one particular room was associated with getting the infection. To prevent the transmission of HCMV infection in this setting, improvement in hygienic behavior ofchildcare workers should be focused.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/genética , Infecções por HIV , Infecções Oportunistas Relacionadas com a AIDS/urina , Infecções Oportunistas Relacionadas com a AIDS/virologia , Criança , Crianças Órfãs/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Infecções por Citomegalovirus/urina , Infecções por Citomegalovirus/virologia , DNA Viral/análise , Demografia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Polimorfismo de Fragmento de Restrição , Prevalência , Tailândia/epidemiologia , Proteínas do Envelope Viral/análiseRESUMO
BACKGROUND: Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality. METHODS: 351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation. RESULTS: The median CD4 of the participants was 57 (IQR: 14-179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; Pâ=â0.005). CONCLUSIONS: In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Cromatografia de Afinidade , Criptococose/diagnóstico , Infecções por HIV/complicações , Sistemas Automatizados de Assistência Junto ao Leito , Tuberculose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/urina , Adulto , Antígenos de Fungos/urina , Criptococose/complicações , Criptococose/mortalidade , Criptococose/urina , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos Estatísticos , Fatores de Risco , Tuberculose/complicações , Tuberculose/mortalidade , Uganda/epidemiologiaRESUMO
Detection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine 'strip test' assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation of treatment. However, few studies using this assay have yet been reported and many questions remain concerning the correct use of the assay, interpretation of results, the role of the assay as an add-on test within existing diagnostic algorithms and the types of further studies needed. In this paper we address a series of questions with the aim of informing the design, conduct and interpretation of future studies. Specifically, we clarify which clinical populations are most likely to derive benefit from use of this assay and how patients enrolled in such studies might best be characterised. We describe the importance of employing a rigorous microbiological diagnostic reference standard in studies of diagnostic accuracy and discuss issues surrounding the specificity of the assay in different geographical areas and potential cross-reactivity with non-tuberculous mycobacteria and other organisms. We highlight the importance of careful procedures for urine collection and storage and the critical issue of how to read and interpret the test strips. Finally, we consider how the assay could be used in combination with other assays and outline the types of studies that are required to build the evidence base concerning its use.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antígenos de Bactérias/urina , Técnicas e Procedimentos Diagnósticos , Lipopolissacarídeos/urina , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Antígenos de Bactérias/metabolismo , Parede Celular/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Mycobacterium tuberculosis/metabolismo , Tuberculose/microbiologia , Tuberculose/urinaAssuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Criptococose/microbiologia , Cryptococcus/isolamento & purificação , Urina/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/urina , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Medula Óssea/microbiologia , Líquido Cefalorraquidiano/microbiologia , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/urina , Feminino , Humanos , Testes de Fixação do Látex , Fígado/microbiologia , UrináliseRESUMO
OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Urina/virologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Idoso , Vírus BK/genética , Contagem de Linfócito CD4 , DNA Viral/análise , Feminino , Humanos , Vírus JC/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/urina , Prevalência , Adulto JovemRESUMO
OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.
OBJETIVO: Avaliar a prevalência de excreção urinaria de vírus JC (VJC) e vírus BK (VBK) em pacientes HIV+ sem sintomas neurológicos. MÉTODOS: Amostras de urina de pacientes HIV+ sem sintomas neurológicos foram testados para a presença de VJC e VBK através da técnica de PCR. As amostras foram triadas para a presença de poliomavírus com par de primers complementares a região precoce do genoma do VBK e do VJC (AgT). A presença foi confirmada através de dois outros ensaios de PCR dirigidos a região do gene VP1 de ambos os vírus. A análise estatística foi realizada com auxílio do teste de Kruskal-Wallis para dados numéricos e Pearson ou Yater para variáveis categóricas. RESULTADOS: Ao todo foram inclusos no estudo 75 pacientes. A prevalência geral de excreção de poliomavírus na urina foi de 67/75 (89,3%). O DNA do vírus VBK foi detectado em 14/75 (18,7%) das amostras de urina, e o DNA do VJC foi detectado em 11/75 (14,7%) das amostras testadas. Ambos os vírus estavam presentes simultaneamente em 42/75 (56%) das amostras de urina. CONCLUSÃO: Encontramos, no presente estudo, uma alta taxa de excreção de VJC, VBK e excreção simultânea em pacientes HIV+. Ainda, esses resultados diferem de outros disponíveis na literatura.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Urina/virologia , Infecções Oportunistas Relacionadas com a AIDS/urina , Infecções Oportunistas Relacionadas com a AIDS/virologia , Vírus BK/genética , DNA Viral/análise , Vírus JC/genética , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/urina , PrevalênciaRESUMO
BACKGROUND: Hospitals in sub-Saharan Africa are inundated with HIV-infected patients and tuberculosis (TB) is the commonest opportunistic infection in this sub-group. Up to one third of TB-HIV co-infected patients fail to produce a sputum sample (sputum scarce) and diagnosis is thus often delayed or missed. We investigated the sensitivity of urine-based methods (Xpert MTB/RIF, LAM strip test and LAM ELISA) in such patients. METHODOLOGY/PRINCIPAL FINDINGS: 281 HIV-infected hospitalised patients with clinically suspected TB provided a spot urine sample. The reference standard was culture positivity for Mycobacterium tuberculosis on ≥1 sputum or extra-pulmonary sample. MTB/RIF was performed using 1 ml of both unprocessed and, when possible, concentrated urine. Each unconcentrated urine sample was also tested using the Clearview LAM ELISA and Alere LAM strip test. 42% (116/242) of patients had culture-proven TB. 18% (20/54) were sputum scarce. In sputum-scarce patients, the sensitivity of urine MTB/RIF and LAM ELISA was 40% (95%CI: 22-61) and 60% (95%CI: 39-78), respectively. Urine MTB/RIF specificity was 98% (95%CI: 95-100). Combined sensitivity of urine LAM ELISA and MTB/RIF was better than MTB/RIF alone [MTB/RIF and LAM: 70% (95%CI: 48-85) vs. MTB/RIF: 40% (95%CI: 22-61), pâ=â0.03]. Significant predictors of urine MTB/RIF positivity were CD4<50 cells/ml (pâ=â0.001), elevated protein-to-creatinine ratio (p<0.001) and LAM ELISA positivity (p<0.001). Urine centrifugation and pelleting significantly increased the sensitivity of MTB/RIF over unprocessed urine in paired samples [42% (95%CI: 26-58) vs. 8% (95%CI: 0-16), p<0.001]. Urine MTB/RIF-generated C(T) values correlated poorly with markers of bacillary burden (smear grade and time-to-positivity). CONCLUSIONS/SIGNIFICANCE: This preliminary study indicates that urine-based MTB/RIF, alone or in combination with LAM antigen detection, may potentially aid the diagnosis of TB in HIV-infected patients with advanced immunosuppression when sputum-based diagnosis is not possible. Concentration of urine prior to MTB/RIF-testing significantly improves sensitivity.