Last data update: May 28, 2024. (Total: 46864 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: McCarthy KD [original query] |
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Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture for detection of Mycobacterium tuberculosis in symptomatic adults: a diagnostic accuracy study
Xie YL , Eichberg C , Hapeela N , Nakabugo E , Anyango I , Arora K , Korte JE , Odero R , van Heerden J , Zemanay W , Kennedy S , Nabeta P , Hanif M , Rodrigues C , Skrahina A , Stevens W , Dietze R , Liu X , Ellner JJ , Alland D , Joloba ML , Schumacher SG , McCarthy KD , Nakiyingi L , Dorman SE . Lancet Microbe 2024 BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. METHODS: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%. FINDINGS: Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0). INTERPRETATION: For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture. FUNDING: US National Institute of Allergy and Infectious Diseases. |
Machine learning to predict bacteriologic confirmation of Mycobacterium tuberculosis in infants and very young children
Smith JP , Milligan K , McCarthy KD , McHembere W , Okeyo E , Musau SK , Okumu A , Song R , Click ES , Cain KP . PLOS Digit Health 2023 2 (5) e0000249 Diagnosis of tuberculosis (TB) among young children (<5 years) is challenging due to the paucibacillary nature of clinical disease and clinical similarities to other childhood diseases. We used machine learning to develop accurate prediction models of microbial confirmation with simply defined and easily obtainable clinical, demographic, and radiologic factors. We evaluated eleven supervised machine learning models (using stepwise regression, regularized regression, decision tree, and support vector machine approaches) to predict microbial confirmation in young children (<5 years) using samples from invasive (reference-standard) or noninvasive procedure. Models were trained and tested using data from a large prospective cohort of young children with symptoms suggestive of TB in Kenya. Model performance was evaluated using areas under the receiver operating curve (AUROC) and precision-recall curve (AUPRC), accuracy metrics. (i.e., sensitivity, specificity), F-beta scores, Cohen's Kappa, and Matthew's Correlation Coefficient. Among 262 included children, 29 (11%) were microbially confirmed using any sampling technique. Models were accurate at predicting microbial confirmation in samples obtained from invasive procedures (AUROC range: 0.84-0.90) and from noninvasive procedures (AUROC range: 0.83-0.89). History of household contact with a confirmed case of TB, immunological evidence of TB infection, and a chest x-ray consistent with TB disease were consistently influential across models. Our results suggest machine learning can accurately predict microbial confirmation of M. tuberculosis in young children using simply defined features and increase the bacteriologic yield in diagnostic cohorts. These findings may facilitate clinical decision making and guide clinical research into novel biomarkers of TB disease in young children. |
Clinical and radiologic factors associated with detection of mycobacterium tuberculosis in children under 5years old using invasive and noninvasive sample collection techniques-Kenya
Smith JP , Song R , McCarthy KD , McHembere W , Click ES , Cain KP . Open Forum Infect Dis 2022 9 (11) ofac560 BACKGROUND: Pediatric tuberculosis (TB) remains a critical public health concern, yet bacteriologic confirmation of TB in children is challenging. Clinical, demographic, and radiological factors associated with a positive Mycobacterium tuberculosis specimen in young children (5years) are poorly understood. METHODS: We conducted a prospective cohort study of young children with presumptive TB and examined clinical, demographic, and radiologic factors associated with invasive and noninvasive specimen collection techniques (gastric aspirate, induced sputum, nasopharyngeal aspirate, stool, and string test); up to 2 samples were taken per child, per technique. We estimated associations between these factors and a positive specimen for each technique using generalized estimating equations (GEEs) and logistic regression. RESULTS: A median (range) of 544 (507-566) samples were obtained for each specimen collection technique from 300 enrolled children; bacteriologic yield was low across all collection techniques (range, 1%-7% from Xpert MTB/RIF or culture), except for lymph node fine needle aspiration (29%) taken for children with cervical lymphadenopathy. Factors associated with positive M. tuberculosis samples across all techniques included prolonged lethargy (median [range] adjusted odds ratio [aOR], 8.1 [3.9-10.1]), history of exposure with a TB case (median [range] aOR, 6.1 [2.9-9.0]), immunologic evidence of M. tuberculosis infection (median [range] aOR, 4.6 [3.7-9.2]), large airway compression (median [range] aOR, 6.7 [4.7-9.5]), and hilar/mediastinal density (median [range] aOR, 2.9 [1.7-3.2]). CONCLUSIONS: Identifying factors that lead to a positive M. tuberculosis specimen in very young children can inform clinical management and increase the efficiency of diagnostic testing in children being assessed for TB. |
Performance of Xpert MTB/RIF and mycobacterial culture on multiple specimen types for diagnosis of tuberculosis disease in young children and clinical characterization according to standardized research case definitions
Click ES , Song R , Smith JP , McHembere W , Fajans M , Hariri P , Okeyo E , McCarthy KD , Gethi D , Odeny L , Musau S , Okumu A , Orwa J , Perez-Velez CM , Wright CA , Andres MM , Marais BJ , Schaaf HS , Graham SM , Cruz AT , Cain KP . Pediatr Infect Dis J 2022 41 (8) 671-677 BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness. |
Need for caution when interpreting Xpert MTB/RIF results for rifampin resistance among children.
Murithi W , Click ES , McCarthy KD , Okeyo E , Sitati R , Anyango I , Okumu A , McHembere W , Song R , Cain K . Int J Tuberc Lung Dis 2021 25 (11) 911-916 BACKGROUND: Recommended by the World Health Organization as an initial diagnostic test for TB in children, Xpert(®) MTB/RIF is widely implemented in many countries, including Kenya.METHODS: Three hundred HIV-positive and negative children (<5 years) were enrolled in Kisumu County, Kenya, from October 2013 to August 2015. Multiple specimen types were collected from each child and tested using Xpert, liquid culture, and phenotypic drug susceptibility testing (DST). Samples positive for rifampin (RIF) resistance on Xpert were tested using line-probe assay and sequencing.RESULTS: Of 32 children with bacteriologically confirmed TB, 27 had positive Xpert results. Of these, 3/27 (11%, 95% CI 4-28) had RIF resistance detected on Xpert, but not by phenotypic DST, line-probe assay, or sequencing. For these three children, five Xpert tests showed RIF resistance; all five tests had semi-quantitative "very low" results and delay or absence of probe D signal, whereas no Xpert results with higher semi-quantitative results showed RIF resistance. All three children responded well to standard TB treatment.CONCLUSIONS: False RIF resistance may be detected in pediatric specimens. Further study is needed to determine if false RIF resistance is associated with low bacterial load. |
Sensitive and feasible specimen collection and testing strategies for diagnosing tuberculosis in young children
Song R , Click ES , McCarthy KD , Heilig CM , McHembere W , Smith JP , Fajans M , Musau SK , Okeyo E , Okumu A , Orwa J , Gethi D , Odeny L , Lee SH , Perez-Velez CM , Wright CA , Cain KP . JAMA Pediatr 2021 175 (5) e206069 IMPORTANCE: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. OBJECTIVE: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. MAIN OUTCOMES AND MEASURES: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. RESULTS: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). CONCLUSIONS AND RELEVANCE: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings. |
Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study
Dorman SE , Schumacher SG , Alland D , Nabeta P , Armstrong DT , King B , Hall SL , Chakravorty S , Cirillo DM , Tukvadze N , Bablishvili N , Stevens W , Scott L , Rodrigues C , Kazi MI , Joloba M , Nakiyingi L , Nicol MP , Ghebrekristos Y , Anyango I , Murithi W , Dietze R , Lyrio Peres R , Skrahina A , Auchynka V , Chopra KK , Hanif M , Liu X , Yuan X , Boehme CC , Ellner JJ , Denkinger CM , Study Team , Cain KP , Agaya J , McCarthy KD . Lancet Infect Dis 2018 18 (1) 76-84 BACKGROUND: The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. METHODS: In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. FINDINGS: Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (-2·7%, -3·9 to -1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. INTERPRETATION: For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. FUNDING: Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases. |
No evidence of Mycobacterium tuberculosis in breast milk of 18 women with confirmed TB disease in Kisumu, Kenya
Click ES , Ouma GS , DeGruy K , Murithi W , Okonji JA , McCarthy KD , Musau S , Okumu A , Alexander H , Posey J , Cain KP . Int J Tuberc Lung Dis 2018 22 (4) 464-465 Mycobacterium tuberculosis complex (MTC) is | comprised of highly related mycobacteria. M. tuberculosis causes tuberculosis (TB) disease primarily in | humans, and M. bovis in cows. However, M. bovis | can cause disease in humans, primarily via ingestion | of infected cow’s milk, and is associated with cervical | lymphadenitis. In humans, TB usually manifests as | pulmonary disease but may affect non-pulmonary | sites. In young children, cervical lymphadenitis is a | common manifestation |
Performance of clinical screening algorithms for tuberculosis intensified case finding among people living with HIV in western Kenya
Modi S , Cavanaugh JS , Shiraishi RW , Alexander HL , McCarthy KD , Burmen B , Muttai H , Heilig CM , Nakashima AK , Cain KP . PLoS One 2016 11 (12) e0167685 OBJECTIVE: To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya. DESIGN: Prospective cohort study. METHODS: PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey. RESULTS: Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9-46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3-86.4)] and men [77.2% (95% CI, 68.3-84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women. CONCLUSIONS: Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services. |
Tuberculosis screening outcomes for newly diagnosed persons living with HIV, Nyanza Province, Kenya, 2009
Burmen B , Modi S , Cavanaugh JS , Muttai H , McCarthy KD , Alexander H , Cain K . Int J Tuberc Lung Dis 2016 20 (1) 79-84 SETTING: Fifteen human immunodeficiency virus (HIV) clinics in Nyanza Region, Western Kenya. OBJECTIVE: To describe routine tuberculosis (TB) screening and diagnostic practices among newly enrolled people living with HIV (PLHIV) prior to the implementation of World Health Organization recommended TB intensified case finding. DESIGN: Retrospective chart abstraction of PLHIV aged 7 years who were newly enrolled in HIV care in July and August 2009, and who had not received antiretroviral treatment in the preceding 2 years or been diagnosed with TB in the previous year. Factors associated with evidence of TB diagnostic evaluation among symptomatic PLHIV were assessed. RESULTS: Of 1020 patients included in the analysis, 995 (98%) were screened for TB at enrolment and 613 (62%) reported TB symptoms. Ninety-six (16%) patients with symptoms had evidence of referral for TB diagnostic evaluation, including patients at large clinics, those with advanced HIV disease and those reporting multiple TB symptoms. Among the 43 (45%) with documented evaluation results, 26 (60%) were diagnosed with TB. CONCLUSION: Although most PLHIV were screened for TB, very few underwent an evaluation, and the proportion diagnosed with TB was very low. Efforts to improve TB screening should focus on standardizing the intensified case finding algorithm and linkage to, and adequate infrastructure for, TB diagnostic evaluation. |
The utility of stool cultures for diagnosing tuberculosis in people living with the human immunodeficiency virus
Oramasionwu GE , Heilig CM , Udomsantisuk N , Kimerling ME , Eng B , Nguyen HD , Thai S , Keo C , McCarthy KD , Varma JK , Cain KP . Int J Tuberc Lung Dis 2013 17 (8) 1023-8 BACKGROUND: Delayed diagnosis of tuberculosis (TB) increases mortality. OBJECTIVE: To evaluate whether stool culture improves the diagnosis of TB in people living with the human immunodeficiency virus (PLHIV). DESIGN: We analysed cross-sectional data of TB diagnosis in PLHIV in Cambodia, Thailand and Viet Nam. Logistic regression was used to assess the association between positive stool culture and TB, and to calculate the incremental yield of stool culture. RESULTS: A total of 1693 PLHIV were enrolled with a stool culture result. Of 228 PLHIV with culture-confirmed TB from any site, 101 (44%) had a positive stool culture; of these, 91 (90%) had pulmonary TB (PTB). After adjusting for confounding factors, a positive stool culture was associated with smear-negative (odds ratio [OR] 26, 95% confidence interval [CI] 12-58), moderately smear-positive (OR 60, 95%CI 23-159) and highly smear-positive (OR 179, 95%CI 59-546) PTB compared with no PTB. No statistically significant association existed with extra-pulmonary TB compared with no extra-pulmonary TB (OR 2, 95%CI 1-5). The incremental yield of one stool culture above two sputum cultures (5%, 95%CI 3-8) was comparable to an additional sputum culture (7%, 95%CI 4-11). CONCLUSION: Nearly half of the PLHIV with TB had a positive stool culture that was strongly associated with PTB. Stool cultures may be used to diagnose TB in PLHIV. |
Using tuberculin skin test as an entry point to screen for latent and active tuberculosis in Thai people living with HIV
Phanuphak N , Varma JK , Kittikraisak W , Teeratakulpisarn N , Phasitlimakul S , Suwanmala P , Pankam T , Burapat T , Tasaneeyapan T , McCarthy KD , Cain KP , Phanuphak P . J Acquir Immune Defic Syndr 2012 60 (4) 384-92 BACKGROUND: Tuberculin skin test (TST) identifies patients highly likely to benefit from isoniazid preventive therapy (IPT) and tuberculosis (TB) prevalence may differ by TST status. We evaluated latent and active TB screening and diagnosis strategies among people living with HIV (PLHIV) incorporating TST as the initial screening step. METHODS: PLHIV attending services at the Thai Red Cross Anonymous Clinic during September 2006-January 2008 were enrolled. TB disease was defined as any positive MTB specimen culture from sputum, urine, stool, lymph node aspiration, and blood. The performance of symptom screening (>1 of: any cough, any fever, night sweats lasting 3 or more weeks in the preceding 4 weeks) and laboratory screening (sputum smear followed by chest radiography and CD4 count) for active TB disease were evaluated according to TST status. RESULTS: We enrolled 604 PLHIV. TST was positive in 151 PLHIV (25.0%). TB disease was diagnosed in 33 PLHIV, including 22 (14.6%) TST-positive and 11 (2.4%) TST-negative PLHIV. We found that an approach of performing MTB culture for all TST-positive PLHIV and symptom screening followed by laboratory screening for all TST-negative PLHIV would identify 196 (32.4%) of 604 PLHIV who would need MTB culture to correctly diagnose 29 (87.9%) of 33 active TB cases. CONCLUSIONS: TST can be used as an initial screening test among PLHIV to identify those at highest risk of active TB disease. Access to MTB culture or other sensitive tests to exclude TB disease is urgently needed to improve TB screening and prevention in resource-limited settings. |
Symptom screen for identification of highly infectious tuberculosis in people living with HIV in southeast Asia
Kim L , Heilig CM , McCarthy KD , Phanuphak N , Chheng P , Nong K , Quy HT , Sar B , Cain KP , Varma JK . J Acquir Immune Defic Syndr 2012 60 (5) 519-24 BACKGROUND: Tuberculosis is the leading cause of death among people living with HIV and frequently transmitted among this susceptible group. Transmission can be reduced by infection control practices. Simple, evidence-based methods to identify patients who should be isolated are not well described in the literature. We sought to identify a simple, sensitive symptom or symptom combination that healthcare providers in resource-limited settings can use to identify and isolate persons living with HIV with highly infectious TB. METHODS: Participants from eight outpatient facilities in Cambodia, Thailand, and Vietnam underwent an extensive evaluation for tuberculosis. Patients with ≥ 1 positive sputum smear and Mycobacterium tuberculosis culture growth from a pulmonary site were defined as having highly infectious tuberculosis. We calculated sensitivity and prevalence of individual symptoms and >1,000 symptom combinations. RESULTS: Of 1,980 participants, 272 (14%) had tuberculosis. Forty percent (n=109) were highly infectious. Sensitivity for detecting highly infectious tuberculosis was highest for having the following symptoms in the past month: weight loss (84%), cough (83%), fever (81%) and fatigue (78%); however, these symptoms were found in 46%-54% of all participants. Having two or three of four symptoms (prevalence, 26%-47%)-weight loss, fever, current cough, and night sweats-was 72-90% sensitive for highly infectious tuberculosis. CONCLUSIONS: The two or three of four symptom combinations of weight loss, fever, current cough, and night sweats, which are the same symptoms comprising the current World Health Organization-recommended tuberculosis diagnostic screen, are sensitive for detecting highly infectious tuberculosis in people living with HIV. |
Nontuberculous mycobacterial disease in patients with human immunodeficiency virus in Southeast Asia
McCarthy KD , Cain KP , Winthrop KL , Udomsantisuk N , Lan NT , Sar B , Kimerling M , Kanara N , Lynen L , Monkongdee P , Tasaneeyapan T , Varma JK . Am J Respir Crit Care Med 2012 185 (9) 981-8 RATIONALE: Although nontuberculous mycobacteria (NTM) are widely documented as a cause of illness among HIV-infected people in the developed world, studies describing the prevalence of NTM disease among HIV-infected people in most resource limited settings are rare. OBJECTIVES: To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia. METHODS: We enrolled people with HIV from three countries in Southeast Asia, and collected pulmonary and extra-pulmonary specimens to evaluate the prevalence of mycobacterial disease. We adapted American Thoracic Society/Infectious Disease Society of America guidelines to classify patients into NTM pulmonary disease, NTM pulmonary disease suspects, NTM disseminated disease, and no NTM categories. MEASUREMENTS AND MAIN RESULTS: In Cambodia, where solid media alone was used, NTM was rare. Of 1,060 patients enrolled in Thailand and Vietnam where liquid culture was performed, 124 (12%) had tuberculosis (TB), while 218 (21%) had NTM. Of 218 patients with NTM, 66 (30%) were classified as NTM pulmonary disease suspects, 9 (4%) with NTM pulmonary disease, and 10 (5%) with NTM disseminated disease. The prevalence of NTM disease was 2% (19/1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART. CONCLUSIONS: While people with HIV frequently have sputum cultures positive for NTM, few meet a strict case definition for NTM disease. Consistent with previous studies, ART was associated with lower odds of having NTM disease. Further studies of NTM in HIV-infected individuals in TB endemic countries are needed to develop and validate case definitions. |
Bloodstream infections among HIV-infected outpatients, Southeast Asia
Varma JK , McCarthy KD , Tasaneeyapan T , Monkongdee P , Kimerling ME , Buntheoun E , Sculier D , Keo C , Phanuphak P , Teeratakulpisarn N , Udomsantisuk N , Dung NH , Lan NT , Yen NT , Cain KP . Emerg Infect Dis 2010 16 (10) 1569-1575 Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single Myco/F Lytic blood culture. Fifty-eight (2.9%) had a clinically significant BSI (i.e., a blood culture positive for an organism known to be a pathogen). Mycobacterium tuberculosis accounted for 31 (54%) of all BSIs, followed by fungi (13 [22%]) and bacteria (9 [16%]). Of patients for whom data were recorded about antiretroviral therapy, 0 of 119 who had received antiretroviral therapy for ≥14 days had a BSI, compared with 3% of 1,801 patients who had not. In multivariate analysis, factors consistently associated with BSI were fever, low CD4+ T-lymphocyte count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness. For HIV-infected outpatients with these risk factors, clinicians should place their highest priority on diagnosing tuberculosis. |
An algorithm for tuberculosis screening and diagnosis in people with HIV
Cain KP , McCarthy KD , Heilig CM , Monkongdee P , Tasaneeyapan T , Kanara N , Kimerling ME , Chheng P , Thai S , Sar B , Phanuphak P , Teeratakulpisarn N , Phanuphak N , Dung NH , Quy HT , Thai LH , Varma JK . N Engl J Med 2010 362 (8) 707-716 BACKGROUND: Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS: We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS: Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS: In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture. Copyright 2010 Massachusetts Medical Society. |
Diagnostic performance and costs of Capilia TB for Mycobacterium tuberculosis complex identification from broth-based culture in Bangkok, Thailand
Ngamlert K , Sinthuwattanawibool C , McCarthy KD , Sohn H , Starks A , Kanjanamongkolsiri P , Anek-vorapong R , Tasaneeyapan T , Monkongdee P , Diem L , Varma JK . Trop Med Int Health 2009 14 (7) 748-53 OBJECTIVES: Broth-based culture (BBC) systems are increasingly being used to detect Mycobacterium tuberculosis complex (MTBC) in resource-limited. We evaluated the performance, time to detection and cost of the Capilia TB identification test from broth cultures positive for acid-fast bacilli (AFB) in Thailand. METHODS: From October-December 2007, broth cultures that grew AFB from specimens submitted by district TB clinics to the Bangkok city laboratory were tested for MTBC using Capilia TB and standard biochemical tests. Isolates that were identified as MTBC by biochemical tests but not by Capilia TB underwent repeat testing using Capilia TB, Accuprobe (Gen-Probe, San Diego, CA, USA) and sequencing. Costs of time, labour, infrastructure and consumables for all procedures were measured. RESULTS: Of 247 isolates evaluated, the sensitivity of Capilia TB was 97% and its true specificity 100% compared with biochemical testing. The median time from specimen receipt to confirmed MTBC identification was 20 days (range 7-53 days) for Capilia TB and 45 days (range 35-79 days) for biochemical testing (P < 0.01). Six isolates that were Capilia TB negative but positive by biochemical testing were confirmed as MTBC and mutations in the mpb64 gene were detected in all. The unit cost of using Capilia TB was 2.67 USD that of biochemical testing was 8.78 USD. CONCLUSIONS: In Thailand, Capilia TB had acceptable sensitivity and specificity, was lower in cost and had shorter turn-around times. Laboratories investing in BBC should consider Capilia TB for identification of MTBC, after validation of performance in their setting. |
Yield of acid-fast smear and mycobacterial culture for tuberculosis diagnosis in people with HIV
Monkongdee P , McCarthy KD , Cain KP , Tasaneeyapan T , Dung NH , Lan NT , Yen NT , Teeratakulpisarn N , Udomsantisuk N , Heilig C , Varma JK . Am J Respir Crit Care Med 2009 180 (9) 903-8 RATIONALE: The World Health Organization (WHO) recently revised its recommendations for tuberculosis (TB) diagnosis in people with HIV. Most studies cited to support these policies involved HIV-uninfected patients and only evaluated sputum specimens. OBJECTIVES: To evaluate the performance of acid fast bacilli (AFB) smear and mycobacterial culture on sputum and non-sputum specimens for TB diagnosis in a cross-sectional survey of HIV-infected patients. METHODS: In Thailand and Vietnam, we enrolled people with HIV regardless of signs or symptoms. Enrolled patients provided three sputum, one urine, one stool, one blood, and, for patients with palpable peripheral adenopathy, one lymph node aspirate specimen for AFB microscopy and mycobacterial culture on solid and broth-based media. We classified any patient with at least one specimen culture positive for Mycobacterium tuberculosis (MTB) as having TB. MAIN RESULTS: Of 1060 patients enrolled, 147 (14%) had TB. Of 126 with pulmonary TB, the incremental yield of performing a third sputum smear over two smears was 2% (95% Confidence Interval, 0-6), 90 (71%) were detected on broth-based culture of the first sputum specimen, and an additional 21 (17%) and 12 (10%) patients were diagnosed with the second and third specimens cultured. Of 82 lymph nodes cultured, 34 (42%) grew MTB. In patients with two negative sputum smears, broth-based culture of three sputum specimens had the highest yield of any testing strategy. CONCLUSIONS: In people with HIV living in settings where mycobacterial culture is not routinely available to all patients, a third sputum smear adds little to the diagnosis of TB, broth-based culture of three sputum specimens diagnoses most TB cases, and lymph node aspiration provides the highest incremental yield of any non-pulmonary specimen test for TB. |
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