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1.
Clin Infect Dis ; 73(4): e870-e877, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398958

RESUMO

BACKGROUND: The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear. METHODS: The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen-negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method. RESULTS: A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9-32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04). CONCLUSIONS: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.


Assuntos
Infecções por HIV , Tuberculose , Adulto , Testes Diagnósticos de Rotina , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Lipopolissacarídeos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
2.
Epidemiology ; 32(6): 811-819, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34292212

RESUMO

BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests can diagnose COVID-19 rapidly and at low cost, but lower sensitivity compared with reverse-transcriptase polymerase chain reaction (PCR) has limited clinical adoption. METHODS: We compared antigen testing, PCR testing, and clinical judgment alone for diagnosing symptomatic COVID-19 in an outpatient setting (10% COVID-19 prevalence among the patients tested, 3-day PCR turnaround) and a hospital setting (40% prevalence, 24-hour PCR turnaround). We simulated transmission from cases and contacts, and relationships between time, viral burden, transmission, and case detection. We compared diagnostic approaches using a measure of net benefit that incorporated both clinical and public health benefits and harms of the intervention. RESULTS: In the outpatient setting, we estimated that using antigen testing instead of PCR to test 200 individuals could be equivalent to preventing all symptomatic transmission from one person with COVID-19 (one "transmission-equivalent"). In a hospital, net benefit analysis favored PCR and testing 25 patients with PCR instead of antigen testing achieved one transmission-equivalent of benefit. In both settings, antigen testing was preferable to PCR if PCR turnaround time exceeded 2 days. Both tests provided greater net benefit than management based on clinical judgment alone unless intervention carried minimal harm and was provided equally regardless of diagnostic approach. CONCLUSIONS: For diagnosis of symptomatic COVID-19, we estimated that the speed of diagnosis with antigen testing is likely to outweigh its lower accuracy compared with PCR, wherever PCR turnaround time is 2 days or longer. This advantage may be even greater if antigen tests are also less expensive.


Assuntos
COVID-19 , Técnicas e Procedimentos Diagnósticos , Testes Diagnósticos de Rotina , Humanos , SARS-CoV-2 , Sensibilidade e Especificidade
3.
Sex Transm Dis ; 48(8S): S71-S77, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34110728

RESUMO

BACKGROUND: Point-of-care (POC) tests enable immediate diagnosis and targeted treatment of sexually transmitted infections (STIs), which could accelerate control of ongoing epidemics. Although older nucleic acid amplification tests have improved the accuracy of laboratory-based tests for STIs, newer POC tests can facilitate control efforts. We sought to review the performance and time to result of POC assays for STIs in the last 10 years. METHODS: The authors performed a PubMed, US National Library of Medicine, National Center for Biotechnology Information search for POC tests for STIs or sexually transmitted diseases. RESULTS: Diagnostic technology for POC assays for STIs has achieved high sensitivity and specificity (>90%) using recent molecular advances in the last 10 years. Three POC tests for chlamydia and gonorrhea and 2 for trichomonas have been cleared by the Food and Drug Administration and can provide rapid results during the clinical encounter. Two POC assays for syphilis are now cleared by the Food and Drug Administration. Other similar POC assays are in development. These "fast followers" have faster time to result and will extend the diagnostic armamentarium at POC. CONCLUSIONS: New technology has improved the performance accuracy of STI POC diagnostics. Innovation in device format has resulted in accurate POC assays, which can decrease the time to result and accelerate the detection and treatment of STIs during the clinical encounter. The full implementation potential of these newer tests will depend on the ability of these tests to achieve Clinical Laboratory Improvement Amendments-waived status so they can be performed by nonlaboratorians with no previous training.


Assuntos
Infecções por Chlamydia , Gonorreia , Doenças Sexualmente Transmissíveis , Infecções por Chlamydia/diagnóstico , Gonorreia/diagnóstico , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Doenças Sexualmente Transmissíveis/diagnóstico , Estados Unidos
4.
J Infect Dis ; 224(6): 976-982, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34191025

RESUMO

BACKGROUND: Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. METHODS: In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. RESULTS: Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. CONCLUSIONS: RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.


Assuntos
Teste para COVID-19 , COVID-19/diagnóstico , Testes Diagnósticos de Rotina , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Animais , Antígenos Virais/análise , Chlorocebus aethiops , Feminino , Humanos , Estudos Longitudinais , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Saliva , Sensibilidade e Especificidade , Células Vero , Adulto Jovem
5.
BMC Infect Dis ; 21(1): 513, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074248

RESUMO

BACKGROUND: In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. METHODS: A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. RESULTS: A total of 81 patients (58.7%) were males, median age 34 (IQR 29  ̶ 40) years, median CD4 cell count of 180 (IQR 68  ̶ 345) cells/µL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0  ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04  ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03  ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74  ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79  ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. CONCLUSION: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.


Assuntos
Carga Bacteriana/métodos , Infecções por HIV/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Antirretrovirais/sangue , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Contagem de Colônia Microbiana , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico , Razão de Chances , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Uganda/epidemiologia
6.
Sci Transl Med ; 13(593)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980576

RESUMO

Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens.


Assuntos
Gonorreia , Doenças Sexualmente Transmissíveis , Baltimore , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Neisseria gonorrhoeae/genética , Sensibilidade e Especificidade , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Uganda
7.
Am J Trop Med Hyg ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33999850

RESUMO

Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.

8.
Am J Obstet Gynecol ; 225(3): 301.e1-301.e14, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33798476

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Inflamação/virologia , Interleucina-1beta/genética , Complicações na Gravidez/virologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/imunologia , Proteínas de Arabidopsis/sangue , COVID-19/complicações , Feminino , Sangue Fetal/química , Expressão Gênica , Humanos , Imunoglobulina G/sangue , Interleucina-6/genética , Proteínas de Membrana/sangue , Doenças Placentárias/virologia , Gravidez , Complicações na Gravidez/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
9.
AIDS ; 35(10): 1585-1595, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831911

RESUMO

OBJECTIVE: The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype. DESIGN: A substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group. METHODS: Plasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug). Drug concentrations were assessed in all matrices. HIV infectivity was assessed using tissue biopsy 'explants' challenged with HIV ex vivo followed by HIV p24 measurement. Flow cytometry evaluated colorectal cell phenotype. RESULTS: Thirty-seven CGW and 54 MSM participated. CGW's colorectal explant p24 was higher than MSM before (0.31 log10, P = 0.046), during (1.01-1.19 log10, P = 0.016) and one week after (0.61 log10, P = 0.011) study drug dosing. Pooling regimens, cervical explant p24 did not differ among visits. CGW had higher plasma maraviroc and colorectal tissue tenofovir diphosphate and lower colorectal tissue emtricitabine (all P < 0.005) compared with MSM. Each study drug's cervical tissue concentrations were more than 10-fold below paired colorectal concentrations (P < 0.001). Cell phenotype sex differences included 4% higher CD38+/CD8+ cells at baseline and 3-7% higher CD69+/CD8+ cells throughout Weeks 24-49 in CGW compared with MSM (P < 0.05). CONCLUSION: Colorectal explants in CGW demonstrated greater HIV infectivity than MSM with and without study drugs. Small differences in adherence, drug concentration and colorectal tissue flow cytometry cannot fully explain this difference.


Assuntos
Fármacos Anti-HIV , Neoplasias Colorretais , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Emtricitabina , Feminino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Leucócitos Mononucleares , Masculino
10.
Int J STD AIDS ; 32(10): 903-910, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33890852

RESUMO

In sub-Saharan Africa (SSA), men are generally difficult to engage in healthcare programs. However, sports gambling centers in SSA can be used as avenues for male engagement in health programs. We offered point-of-care HIV and syphilis testing for men located at five gambling centers in Uganda and assessed HIV risky sexual behavior. Among 507 men, 0.8% were HIV-positive and 3.8% had syphilis. Risky sexual behavior included condomless sex with partner(s) of unknown HIV status (64.9%), having multiple sexual partners (47.8%), engaging in transactional sex (15.5%), and using illicit drugs (9.3%). The majority at 64.5% were nonalcohol consumers, 22.9% were moderate users, and 12.6% had hazardous consumption patterns. In 12 months of follow-up, the incidence rate of syphilis was 0.95 (95% CI: 0.82-1.06) among 178 men. Thus, men in SSA have a high prevalence of syphilis and risky sexual behavior which should be more effectively addressed to reduce the risk of HIV acquisition.


Assuntos
Jogo de Azar , Infecções por HIV , Doenças Sexualmente Transmissíveis , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , Testes Imediatos , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/epidemiologia , Uganda/epidemiologia
12.
J Clin Invest ; 131(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571162

RESUMO

Multiple studies have shown loss of severe acute respiratory syndrome coronavirus 2-specific (SARS-CoV-2-specific) antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from coronavirus disease 2019 (COVID-19). However, memory B cells (MBCs) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multidimensional flow cytometric analysis of S protein receptor binding domain-specific (S-RBD-specific) MBCs in cohorts of ambulatory patients with COVID-19 with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 days (range, 39-104 days) after symptom onset. We detected S-RBD-specific class-switched MBCs in 13 of 14 participants, failing only in the individual with the lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBCs (rMBCs) made up the largest proportion of S-RBD-specific MBCs in both cohorts. FCRL5, a marker of functional memory on rMBCs, was more dramatically upregulated on S-RBD-specific rMBCs after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched rMBCs that resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after mild or severe disease.


Assuntos
Linfócitos B/imunologia , COVID-19/imunologia , SARS-CoV-2 , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Sítios de Ligação/imunologia , COVID-19/virologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Imunidade Celular , Switching de Imunoglobulina , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo
13.
Clin Infect Dis ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638976

RESUMO

BACKGROUND: The urine lipoarabinomannan (LAM) antigen test is a TB diagnostic test with highest sensitivity in individuals with advanced HIV. Its role in TB diagnostic algorithms for HIV positive outpatients remains unclear. METHODS: ACTG A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen negative HIV positive adults initiating ART with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence and time to TB using Kaplan-Meier method. RESULTS: A5274 enrolled 850 participants, 53% were male and median CD4 count was 18 cells/µL (IQR: 9, 32). Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive [21 (7%); 7 (2%) in empiric and IPT arms, respectively]. Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in empiric and IPT arms, respectively (p=0.88). TB incidence remained higher (4.6% vs. 2%, p=0.04) and time to TB remained faster in the empiric arm (p=0.04). CONCLUSIONS: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy and Xpert testing, LAM testing identified an additional 5% of individuals with TB. . Positive LAM results did not change mortality or TB incidence.

14.
Int J STD AIDS ; 32(6): 510-516, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33612012

RESUMO

The aim of this study was to establish the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in key populations at increased risk of transmission of HIV. Additionally, we aimed to identify the associated risk factors for asymptomatic sexually transmitted infections (STIs) and evaluate the acceptability of self-collected samples. Asymptomatic people living with HIV (PLHIV) in the following categories were offered testing: discordant couples, young adults, pregnant patients and those attending the 'most-at-risk-population' clinic. Patients provided first-pass urine, self-collected vaginal swabs or both to test for NG and CT by polymerase chain reaction using BD ProbeTec™. Patients also completed an acceptability questionnaire, including the negative partner of an HIV-positive participant. Three hundred and sixty-three PLHIV had an STI screen. Asymptomatic STIs were only diagnosed in women (prevalence 5.7%), overall prevalence 3.9% (n = 14). Factors independently associated with an STI in women were being under 25 years (OR 9.63 95% CI 1.56-59.5) and having more than one sexual partner (OR 8.06 95% CI 1.07-60.6). Four hundred and seven completed the acceptability questionnaire. More than 95% of patients found self-sampling easy and comfortable and 83.8% would believe the results. Women significantly preferred the option of self-sampling, 56.9% versus 29.3% of men (p < 0.001). Acceptability of self-sampling was high. Young women with or at risk of HIV are an important target for STI testing regardless of symptoms. There is need for diagnostic tests that are inexpensive, rapid and accurate especially in resource-limited settings.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Doenças Sexualmente Transmissíveis , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Feminino , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , Neisseria gonorrhoeae , Gravidez , Prevalência , Uganda/epidemiologia , Adulto Jovem
15.
BMC Infect Dis ; 21(1): 63, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435896

RESUMO

BACKGROUND: Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients. METHODS: HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard. RESULTS: Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28-39) years and CD4 count 112 (23-308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6-77.8) and 53.7% (95%CI 47.7-59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0-75.7) and 95.8% (95%CI 92.8-97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5-93.9) and 51.6% (95%CI 45.6-57.5) respectively; 86.2% (95%CI 75.3-93.5) and 48.1% (95%CI 40.7-55.6) among inpatients and 93.8% (95%CI 69.8-99.8) and 58.0% (95%CI 47.7-67.8) among outpatients respectively. CONCLUSION: In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Coinfecção/diagnóstico , HIV/isolamento & purificação , Radiografia Pulmonar de Massa/métodos , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Contagem de Linfócito CD4 , Coinfecção/epidemiologia , Coinfecção/virologia , Confiabilidade dos Dados , Feminino , Recursos em Saúde , Humanos , Masculino , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Uganda/epidemiologia
16.
Clin Infect Dis ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33479756

RESUMO

BACKGROUND: Individuals can test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by molecular assays following the resolution of their clinical disease. Recent studies indicate that SARS-CoV-2 antigen-based tests are likely to be positive early in the disease course, when there is an increased likelihood of high levels of infectious virus. METHODS: Upper respiratory specimens from 251 participants with coronavirus disease 2019 symptoms (≤7 days from symptom onset) were prospectively collected and tested with a lateral flow antigen test and a real-time polymerase chain reaction (rt-PCR) assay for detection of SARS-CoV-2. Specimens from a subset of the study specimens were utilized to determine the presence of infectious virus in the VeroE6TMPRSS2 cell culture model. RESULTS: The antigen test demonstrated a higher positive predictive value (90%) than rt-PCR (70%) when compared to culture-positive results. The positive percentage agreement for detection of infectious virus for the antigen test was similar to rt-PCR when compared to culture results. CONCLUSIONS: The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture positivity represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. SARS-CoV-2 antigen testing can facilitate low-cost, scalable, and rapid time-to-result, while providing good risk determination of those who are likely harboring infectious virus, compared to rt-PCR.

18.
J Clin Microbiol ; 59(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33208477

RESUMO

Rapid point-of-care tests (POCTs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies vary in performance. A critical need exists to perform head-to-head comparisons of these assays. The performances of 15 different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies were compared on a well-characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (collected an average of 45 days after symptom onset) were used to assess sensitivity. Sixty samples from the prepandemic era (negative control) that were known to represent infections with other respiratory viruses (rhinoviruses A, B, and C and/or coronavirus 229E, HKU1, and NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed using five lateral flow assays (LFAs) and a panel of 272 longitudinal samples from 47 patients for whom the time since symptom onset was known. Among the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55% to 97% and from 78% to 100%, respectively. Assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0% to 88% and 80% to 100% for IgM and from 25% to 95% and 90% to 100% for IgG, respectively. Longitudinal testing revealed that the median times after symptom onset to a positive result were 7 days (interquartile range [IQR], 5.4 to 9.8) for IgM and 8.2 days (IQR, 6.3 to 11.3) for IgG. The testing performances differed widely among LFAs, with greatest amount of variation related to the sensitivity of the assays. The IgM band was the band most likely to misclassify prepandemic samples. The appearances of IgM and IgG bands occurred almost simultaneously.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Testes Imediatos , SARS-CoV-2/isolamento & purificação , Anticorpos Antivirais/sangue , COVID-19/sangue , Reações Cruzadas , Humanos , Imunoensaio , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Soroconversão
19.
Sex Transm Infect ; 97(4): 312-316, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33082237

RESUMO

OBJECTIVES: The emergence of multidrug-resistant Neisseria gonorrhoeae (NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda. METHODS: From March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed. RESULTS: Of the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime. CONCLUSIONS: We established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions.

20.
BMC Public Health ; 20(1): 1855, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272226

RESUMO

BACKGROUND: In 2018, Uganda started only 65% of persons with incident tuberculosis on treatment. Pretreatment loss to follow up is an important contributor to suboptimal treatment coverage. We aimed to describe the patient and health facility-level characteristics associated with pretreatment loss to follow up among patients diagnosed with pulmonary tuberculosis at public health facilities in Uganda. METHODS: At ten public health facilities, laboratory register data was used to identify patients aged ≥ 15 years who had a positive Xpert®MTB/RIF test. Initiation on TB treatment was ascertained using the clinical register. Factors associated with not being initiated on TB treatment within two weeks of diagnosis were examined using a multilevel logistic regression model accounting for clustering by health facility. RESULTS: From January to June 2018, 510 patients (61.2% male and 31.5% HIV co-infected) were diagnosed with tuberculosis. One hundred (19.6%) were not initiated on TB treatment within 2 weeks of diagnosis. Not having a phone number recorded in the clinic registers (aOR 7.93, 95%CI 3.93-13.05); being HIV-infected (aOR 1.83; 95% CI: 1.09-3.26) and receiving care from a high volume health facility performing more than 12 Xpert tests per day (aOR 4.37, 95%CI 1.69-11.29) and were significantly associated with pretreatment loss to follow up. CONCLUSION: In public health facilities in Uganda, we found a high rate of pretreatment loss to follow up especially among TBHIV co-infected patients diagnosed at high volume health facilities. Interventions to improve the efficiency of Xpert® MTB/RIF testing, including monitoring of the TB care cascade should be developed and implemented.


Assuntos
Perda de Seguimento , Tuberculose/diagnóstico , Adulto , Coinfecção/complicações , Feminino , Seguimentos , Programas Governamentais , Infecções por HIV/complicações , Humanos , Laboratórios , Masculino , Assistência Médica , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Conhecimento do Paciente sobre a Medicação , Tuberculose Pulmonar/diagnóstico , Uganda/epidemiologia
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