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1.
BMC Infect Dis ; 23(1): 447, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37400753

ABSTRACT

BACKGROUND: To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT). METHODS: This observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site. DISCUSSION: By targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care. TRIAL REGISTRATION: NCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Point-of-Care Systems , Triage , Tuberculosis/diagnosis , Point-of-Care Testing , Sensitivity and Specificity , Biomarkers
2.
Clin Infect Dis ; 74(12): 2136-2141, 2022 07 06.
Article in English | MEDLINE | ID: mdl-34550342

ABSTRACT

BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a "TB score" based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. METHODS: Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). RESULTS: When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI], .91-.97), sensitivity of 87% (95% CI, 77-93%) and specificity of 94% (88-97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75-97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI, .83-.94), 80% sensitivity (95% CI, 76-85%) and 94% specificity (95% CI, 91-96%). CONCLUSIONS: Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.


Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis , Adult , HIV Infections/diagnosis , Hematologic Tests , Humans , Mycobacterium tuberculosis/genetics , Prospective Studies , Sensitivity and Specificity , Tuberculosis/diagnosis
3.
Emerg Med J ; 37(5): 314-318, 2020 May.
Article in English | MEDLINE | ID: mdl-32139514

ABSTRACT

INTRODUCTION: First attempt intubation success is used by many prehospital services as a marker of quality and safety. An increasing complication rate is associated with repeated intubation attempts. The aim of this study was to identify changes to intubation technique following a failed intubation attempt. METHODS: LifeFlight Retrieval Medicine provides aeromedical retrieval services in Queensland, Australia. This retrospective study identified cases of failed intubation attempts from an electronic database registry over a 41-month period from March 2015 to July 2018. These data were analysed using descriptive statistics. RESULTS: Of the 762 patients who required intubation 758 (99.5%) were successfully intubated, with 684 intubated at the first attempt (89.8%; 95% CI: 0.87 to 0.92). There was no difference in first attempt success between direct and video laryngoscopy (511/563 (90.8%) vs 172/194 (88.6%) p=0.38), trauma or medical (374/419 (89.3%) vs 310/343 (90.4%), p=0.61), primary or interhospital missions (329/370 (88.7%) vs 355/392 (90.8%), p=0.33). 78 cases of failed first attempt intubations were identified. In 65 of these cases, intubation was successful at the second attempt. A single change was made to the intubation procedure prior to a second successful attempt in 28/78 cases (35.9%), and more than one change was made in 41/78 (52.6%). The changes included the operator, intubation device, patient position, intubating aid and external laryngeal manipulation. No change between attempts was recorded in 9/78 (11.5%). 9 cases were successfully intubated at the third attempt, and changes prior to the third attempt included operator, device and intubating aid. CONCLUSION: Although a high overall intubation success was found, one in ten patients who were intubated had a failed first attempt. The majority of successful subsequent attempts were preceded by at least one change to intubating technique. Intubating clinicians need the ability to identify and correct issues leading to a failed first attempt.


Subject(s)
Air Ambulances , Intubation, Intratracheal/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Queensland , Registries , Retrospective Studies , Treatment Failure
4.
Clin Infect Dis ; 69(10): 1724-1730, 2019 10 30.
Article in English | MEDLINE | ID: mdl-30668657

ABSTRACT

BACKGROUND: Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT). METHODS: Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes. RESULTS: ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability. CONCLUSIONS: The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.


Subject(s)
Interferon-gamma Release Tests , Interferon-gamma/blood , Reagent Kits, Diagnostic , Tuberculosis/diagnosis , Adolescent , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Child , Cohort Studies , Female , Humans , Male , Mycobacterium tuberculosis/immunology , ROC Curve , Reproducibility of Results , Tuberculosis/blood , Tuberculosis/immunology , Tuberculosis Vaccines/administration & dosage , Tuberculosis Vaccines/immunology
5.
Am J Respir Crit Care Med ; 196(5): 638-648, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28737960

ABSTRACT

RATIONALE: Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (Mtb) infection, which predisposes individuals to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability. OBJECTIVES: To improve the consistency of serial QuantiFERON-TB testing algorithms and provide a data-driven definition of conversion. METHODS: Sources of QuantiFERON-TB variability were assessed, and optimal procedures were identified. Distributions of IFN-γ response levels were analyzed in healthy adolescents, Mtb-unexposed control subjects, and patients with pulmonary tuberculosis. MEASUREMENTS AND MAIN RESULTS: Individuals with no known Mtb exposure had IFN-γ values less than 0.2 IU/ml. Among individuals with IFN-γ values less than 0.2 IU/ml, 0.2-0.34 IU/ml, 0.35-0.7 IU/ml, and greater than 0.7 IU/ml, tuberculin skin test positivity results were 15%, 53%, 66%, and 91% (P < 0.005), respectively. Together, these findings suggest that values less than 0.2 IU/ml were true negatives. In short-term serial testing, "uncertain" conversions, with at least one value within the uncertainty zone (0.2-0.7 IU/ml), were partly explained by technical assay variability. Individuals who had a change in QuantiFERON-TB IFN-γ values from less than 0.2 to greater than 0.7 IU/ml had 10-fold higher tuberculosis incidence rates than those who maintained values less than 0.2 IU/ml over 2 years (P = 0.0003). By contrast, "uncertain" converters were not at higher risk than nonconverters (P = 0.229). Eighty-seven percent of patients with active tuberculosis had IFN-γ values greater than 0.7 IU/ml, suggesting that these values are consistent with established Mtb infection. CONCLUSIONS: Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition (an increase from IFN-γ <0.2 to >0.7 IU/ml) would allow more definitive detection of recent Mtb infection and potentially improve identification of those more likely to develop disease.


Subject(s)
Interferon-gamma/blood , Interferon-gamma/immunology , Mycobacterium tuberculosis/immunology , Tuberculin Test/methods , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/immunology , Adolescent , Adult , Female , Humans , Male , Reproducibility of Results , Tuberculin Test/statistics & numerical data
6.
Air Med J ; 37(6): 371-373, 2018.
Article in English | MEDLINE | ID: mdl-30424855

ABSTRACT

OBJECTIVE: Traumatic cardiac arrest (TCA) has been associated with poor outcome, but there are survivors with good neurological outcome. Treatment of hypoxia plays a key part in resuscitation algorithms, but little evidence exists on the ideal method of airway management in TCA. METHODS: LifeFlight Retrieval Medicine is an aeromedical retrieval service based in Queensland, Australia. Data regarding all intubations performed over a 28-month period were accessed from an electronic airway registry. RESULTS: 13/22 TCA patients were male, age range 2-81 years. 7/22 (31.8%) survived to hospital admission. During the same period 271 patients were intubated due to trauma, but were not in cardiac arrest (N-TCA). There was no difference in the likelihood of difficult laryngoscopy in the TCA group (16/22 (72.7%) compared to N-TCA (215/271 (79.3%); p = 0.46). The first attempt success rate was similar in TCA group (19/22 (86.4%)) and N-TCA (241/271 (88.9%) p = 0.71.). TCA patients were more likely to be intubated while lying on the ground than the N-TCA group (11/22 (50%) versus 17/271 (6.3%) p = <0.001). CONCLUSION: Resuscitation for predominantly blunt TCA is not futile. The endotracheal intubation first attempt success rate for TCA is comparable to that of N-TCA trauma patients.


Subject(s)
Air Ambulances , Intubation, Intratracheal/statistics & numerical data , Out-of-Hospital Cardiac Arrest/therapy , Wounds and Injuries/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Air Ambulances/statistics & numerical data , Child , Child, Preschool , Female , Humans , Intubation, Intratracheal/methods , Intubation, Intratracheal/mortality , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/mortality , Queensland , Wounds and Injuries/complications , Wounds and Injuries/mortality , Young Adult
7.
Lancet Microbe ; 2(10): e518-e526, 2021 10.
Article in English | MEDLINE | ID: mdl-34617068

ABSTRACT

BACKGROUND: Direct bronchial spread of tuberculosis was extensively described in pre-antibiotic human pathology literature but this description has been overlooked in the post-antibiotic era, in which most pathology data come from animal models that emphasise the granuloma. Modern techniques, such as [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET-CT scans, might provide further insight. Our aim was to understand normal early tuberculosis resolution patterns on pulmonary PET-CT scans in treated patients with tuberculosis who were subsequently cured. METHODS: In this observational analysis, we analysed data from PredictTB, an ongoing, prospective, randomised clinical trial that examined sequential baseline and week 4 FDG-PET-CT scans from participants successfully treated (sputum culture negative 18 months after enrolment) for drug-susceptible pulmonary tuberculosis in South Africa and China. Participants who were aged 18-75 years, GeneXpert MTB/RIF positive for tuberculosis and negative for rifampicin resistance, had not yet started tuberculosis treatment, had not been treated for active tuberculosis within the previous 3 years, and met basic safety laboratory criteria were included and participants with diabetes, HIV infection, or with extrapulmonary tuberculosis including pleural tuberculosis were excluded. Scans were assessed by two readers for the location of tuberculosis lesions (eg, cavities and consolidations), bronchial thickening patterns, and changes from baseline to week 4 of treatment. FINDINGS: Among the first 124 participants (enrolled from June 22, 2017, to Sept 27, 2018) who were successfully treated, 161 primarily apical cavitary lesions were identified at baseline. Bronchial thickening and inflammation linking non-cavitary consolidative lesions to cavities were observed in 121 (98%) of 124 participants' baseline PET-CT scans. After 4 weeks of treatment, 21 (17%) of 124 participants had new or expanding lesions linked to cavities via bronchial inflammation that were not present at baseline, particularly participants with two or more cavities at baseline and participants from South Africa. INTERPRETATION: In participants with pulmonary tuberculosis who were subsequently cured, the location of cavitary and non-cavitary lesions at baseline and new lesions at week 4 of treatment suggest a cavitary origin of disease and bronchial spread through the lungs. Bronchial spread from cavities might play a larger role in the spread of pulmonary tuberculosis than has been appreciated. Elucidating cavity lesion dynamics and Mycobacterium tuberculosis viability within cavities might better explain treatment outcomes and why some patients are cured and others relapse. FUNDING: Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership, China Ministry of Science and Technology, National Natural Science Foundation of China, and National Institutes of Health. TRANSLATIONS: For the Chinese, Afrikaans and Xhosa translations of the abstract see Supplementary Materials section.


Subject(s)
HIV Infections , Tuberculosis, Lymph Node , Tuberculosis, Pulmonary , Anti-Bacterial Agents/therapeutic use , Fluorodeoxyglucose F18/therapeutic use , HIV Infections/drug therapy , Humans , Inflammation/drug therapy , Positron Emission Tomography Computed Tomography , Prospective Studies , Rifampin/therapeutic use , Sensitivity and Specificity , Tuberculosis, Lymph Node/drug therapy , Tuberculosis, Pulmonary/diagnostic imaging , United States
8.
EJNMMI Res ; 10(1): 8, 2020 Feb 10.
Article in English | MEDLINE | ID: mdl-32040770

ABSTRACT

BACKGROUND: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. RESULTS: Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. CONCLUSIONS: Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.

9.
Int J Nurs Pract ; 14(5): 366-72, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18808537

ABSTRACT

Magnet hospitals are recognized institutions of nursing excellence that provide an environment for the promotion of nursing and high-quality patient care. The Magnet Recognition Program, developed by the American Nurses Credentialing Centre, acknowledges health-care institutions that not only attract and retain nursing staff but also recognize nursing excellence in the delivery of quality patient care. Our study aimed to adapt the existing Practice Environment Scale to the Australian context and to pilot its use in measuring the nursing practice environment at a metropolitan hospital in Sydney, Australia. Nursing staff from four wards at a 400 bed major metropolitan acute general hospital in Sydney, Australia completed a self-administered questionnaire about their practice environment. Data were compared with the published norms from magnet and non-magnet hospitals in the USA, and means of two subscales were not significantly different from magnet hospital means. Hospitals could benefit from undertaking a similar practice environment baseline measure prior to applying for accreditation, thus enabling targeting of pre-identified service gaps and areas for improvement.


Subject(s)
Hospitals , Nursing Staff, Hospital , Nursing , Adult , Aged , Female , Humans , Male , Middle Aged , New South Wales , Surveys and Questionnaires
10.
Int J Nurs Stud ; 88: 85-96, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30219697

ABSTRACT

OBJECTIVE: The aim of this paper is to systematically review studies that discuss the experiences of vulnerable populations participating in research on sensitive topics. DESIGN: Systematic review performed according to PRISMA guidelines. DATA SOURCES: Thirteen databases were searched, locating 197 articles. Following removal of duplicates, screening and full text review, 31 studies remained to be critically appraised. REVIEW METHODS: As there was a mix of qualitative and quantitative articles, the Critical Appraisal Skills Program (CASP) toolkit and Effective Public Health Practice Project (EPHPP) tool were used to appraise the methodological quality of the articles. Following critical appraisal, the remaining 11 articles were synthesised narratively to identify common themes across the studies. RESULTS: Despite some reports of distress, responses from participants were overwhelmingly positive. There was a strong link between symptomatology and potential for distress; however, the majority of those who did experience some level of discomfort stated they would still participate in future research. Three major themes were extracted: "It was worth it"; "Even if it hurt, I would do it again" and "Risk or benefit: fixing the location on the continuum". CONCLUSION: Although researchers frequently experience obstacles and the phenomenon known as "gatekeeping" when attempting to conduct research amongst vulnerable populations, there is little evidence of harm to participants. On the contrary, there is evidence of benefit for participants and evidence that they are willing to participate if given the opportunity. Although well-meaning, the actions of gatekeepers are not only paternalistic, they could be further marginalising vulnerable populations by denying them the benefits to be gained from research designed to identify and begin addressing their needs.


Subject(s)
Nursing Research , Vulnerable Populations , Humans , Professional Competence
11.
Gates Open Res ; 1: 9, 2017 Nov 06.
Article in English | MEDLINE | ID: mdl-29528048

ABSTRACT

Background: By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment. Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C. Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832.

12.
Int Breastfeed J ; 12: 16, 2016.
Article in English | MEDLINE | ID: mdl-28405212

ABSTRACT

BACKGROUND: Optimal breastfeeding has benefits for the mother-infant dyads. This study investigated the prevalence and determinants of cessation of exclusive breastfeeding (EBF) in the early postnatal period in a culturally and linguistically diverse population in Sydney, New South Wales, Australia. METHODS: The study used routinely collected perinatal data on all live births in 2014 (N = 17,564) in public health facilities in two Local Health Districts in Sydney, Australia. The prevalence of mother's breastfeeding intention, skin-to-skin contact, EBF at birth, discharge and early postnatal period (1-4 weeks postnatal) were estimated. Multivariate logistic regression models that adjusted for confounders were conducted to determine association between cessation of EBF in the early postnatal period and socio-demographic, psychosocial and health service factors. RESULTS: Most mothers intended to breastfeed (92%), practiced skin-to-skin contact (81%), exclusively breastfed  at delivery (90%) and discharge (89%). However, the prevalence of EBF declined (by 27%) at the early postnatal period (62%). Younger mothers (<20 years) and mothers who smoked cigarettes in pregnancy were more likely to cease EBF in the early postnatal period compared to older mothers (20-39 years) and those who reported not smoking cigarettes, respectively [Adjusted Odds Ratio (AOR) =2.7, 95%CI 1.9-3.8, P <0.001 and AOR = 2.5, 95%CI 2.1-3.0, P <0.001, respectively]. Intimate partner violence, assisted delivery, low socio-economic status, pre-existing maternal health problems and a lack of partner support were also associated with early cessation of EBF in the postnatal period. CONCLUSIONS: Our findings suggest that while most mothers intend to breastfeed, and commence EBF at delivery and at discharge, the maintenance of EBF in the early postnatal period is sub-optimal. This highlights the need for efforts to promote breastfeeding in the wider community along with targeted actions for disadvantaged groups and those identified to be at risk of early cessation of EBF to maximise impact.

13.
Nat Med ; 22(10): 1094-1100, 2016 10.
Article in English | MEDLINE | ID: mdl-27595324

ABSTRACT

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.


Subject(s)
Lung/diagnostic imaging , Mycobacterium tuberculosis/genetics , RNA, Messenger/metabolism , Tuberculosis, Pulmonary/diagnostic imaging , Adolescent , Adult , Aged , Antitubercular Agents/therapeutic use , Bronchoalveolar Lavage Fluid , Female , Humans , Lung/metabolism , Lung/microbiology , Male , Middle Aged , Positron Emission Tomography Computed Tomography , South Africa , Sputum/metabolism , Tuberculosis, Pulmonary/drug therapy , Young Adult
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