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ABSTRACT: Despite rapid economic development, China has not yet incorporated into its national childhood immunization program vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b. Both vaccines can prevent pneumonia, the leading infectious disease killer of young children in China. In contrast, the other World Health Organization member nations with the ten largest birth cohorts have included H. influenzae type b in their national childhood immunization programs, and many of the world's wealthiest and poorest countries have done the same with S. pneumoniae. In this article we review what is known about S. pneumoniae and H. influenzae type b in China, and we make recommendations for how to accelerate the use of vaccines against these pathogens in that country. We propose that China adopt a "Chinese Accelerated Vaccine Initiative" modeled after other successful global programs. This broad effort would marshal the evidence and commitment needed to change vaccine policy, then develop and implement a plan for a sustainable, affordable supply of these and other new vaccines.
Health Affairs 11/2012; 31(11):2545-53. · 4.31 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2012; 16(9):1138. · 2.73 Impact Factor
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Nittaya Phanuphak, Jay K Varma,
Wanitchaya Kittikraisak,
Nipat Teeratakulpisarn,
Saranya Phasitlimakul,
Pailin Suwanmala,
Tippawan Pankam,
Thanyathorn Burapat,
Theerawit Tasaneeyapan,
Kimberly D McCarthy,
Kevin P Cain,
Praphan Phanuphak
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ABSTRACT: Tuberculin skin test (TST) identifies patients highly likely to benefit from isoniazid preventive therapy 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.
PLHIV attending services at the Thai Red Cross Anonymous Clinic during September 2006 to January 2008 were enrolled. TB disease was defined as any positive Mycobacterium tuberculosis (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.
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.
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.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 60(4):384-92. · 4.43 Impact Factor
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ABSTRACT: Tuberculosis (TB) 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.
Participants from 8 outpatient facilities in Cambodia, Thailand, and Vietnam underwent an extensive evaluation for TB. Patients with ≥1 positive sputum smear and Mycobacterium tuberculosis culture growth from a pulmonary site were defined as having highly infectious TB. We calculated sensitivity and prevalence of individual symptoms and >1000 symptom combinations.
Of 1980 participants, 272 (14%) had TB. Forty percent (n = 109) were highly infectious. Sensitivity for detecting highly infectious TB was highest for having the following symptoms in the past month as follows: weight loss (84%), cough (83%), fever (81%), and fatigue (78%); however, these symptoms were found in 46%-54% of all participants. Having 2 or 3 of 4 symptoms (prevalence, 26%-47%)-weight loss, fever, current cough, and night sweats-was 72%-90% sensitive for highly infectious TB.
The 2 or 3 of 4 symptom combinations of weight loss, fever, current cough, and night sweats, which are the same symptoms comprising the current World Health Organization-recommended TB diagnostic screen, are sensitive for detecting highly infectious TB in people living with HIV.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 60(5):519-24. · 4.43 Impact Factor
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Xiaoling Deng,
Lu Ran,
Shuyu Wu,
Bixia Ke,
Dongmei He,
Xingfen Yang,
Yonghui Zhang,
Changwen Ke,
John D Klena,
Meiying Yan,
Zijian Feng,
Biao Kan,
Xin Liu,
Matthew Mikoleit, Jay K Varma
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ABSTRACT: Salmonella is one of the most common foodborne pathogens in humans. Laboratory-based surveillance for non-typhoidal Salmonella infection was conducted in Guangdong Province, China to improve understanding about the disease burden and detection of dispersed outbreaks. Salmonella isolated from patients with diarrhea were sent from 16 sentinel hospitals to local public health laboratories for confirmation, serotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). PFGE patterns were analyzed to identify clusters representing potential outbreaks. Between September 2009 and October 2010, 352 (4%) Salmonella isolates were obtained from 9167 stool specimens. Salmonella enterica serotype Typhimurium (45%) and Salmonella enterica serotype Enteritidis (13%) were the most common serotypes, and multidrug resistance was high, especially in Salmonella Typhimurium isolates. PFGE patterns of obtained Salmonella isolates were found to be diverse, but a unique PFGE pattern comprising 53 Salmonella Typhimurium isolates were found to occur almost exclusively in infants. Epidemiologic studies are ongoing to determine whether a common exposure is the source of the Salmonella Typhimurium strain frequently isolated from infants.
Foodborne Pathogens and Disease 02/2012; 9(4):305-12. · 2.26 Impact Factor
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Kimberly D McCarthy,
Kevin P Cain,
Kevin L Winthrop,
Nibondh Udomsantisuk,
Nguyen T N Lan,
Borann Sar,
Michael E Kimerling,
Nong Kanara,
Lut Lynen,
Patama Monkongdee,
Theerawit Tasaneeyapan, Jay K Varma
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ABSTRACT: 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.
To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia.
We enrolled people with HIV from three countries in Southeast Asia and collected pulmonary and extrapulmonary 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.
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 and 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 of 1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART.
Although 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 tuberculosis-endemic countries are needed to develop and validate case definitions.
American Journal of Respiratory and Critical Care Medicine 02/2012; 185(9):981-8. · 11.08 Impact Factor
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ABSTRACT: Although international clinical guidelines generally recommend performing bacterial stool culture in patients with acute diarrhea and fever and discourage routine antibiotic prescribing, clinical practice varies. Understanding practice patterns can help health officials assess the sensitivity of laboratory-based enteric infection surveillance systems and the need to improve antibiotic prescribing practices. We surveyed physicians in Guangdong province, China, to measure their practices for patients with acute diarrhea. A standardized questionnaire was used to interview physicians working in hospitals participating in a Salmonella surveillance system in Guangdong, China. The questionnaire asked physicians about their routine practice for patients with diarrhea, including how they managed the last patient they had seen with acute diarrhea. We calculated the odds ratio and 95% confidence interval for factors associated with ordering a stool culture and for prescribing antibiotics. We received surveys from 237 physicians across 22 hospitals in Guangdong. For the last patient with diarrhea whom they had evaluated, 134 (57%) reported ordering a stool culture. The most common reasons for not ordering a stool culture included that it takes too long to receive the result, that the patient is not willing to pay for the test, and that the patient's illness was too mild to warrant testing. Most physicians prescribed at least one medication for the last patient with diarrhea whom they had evaluated. Of the 237 physicians surveyed, 153 (65%) prescribed antibiotics, 135 (57%) probiotics, and 115 (49%), a gastric mucosal protective drug. In conclusion, physicians in Guangdong, China, reported high rates of ordering bacterial stool cultures from patients with diarrhea, possibly associated with their hospital's participation in a special surveillance project. The high rate of antibiotic prescribing suggests that efforts to promote judicious antibiotic use, such as physician education, are needed.
Foodborne Pathogens and Disease 01/2012; 9(1):47-53. · 2.26 Impact Factor
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ABSTRACT: In the past 50 years, the United States has made major advances in human health surveillance, research and outbreak investigation that have helped reduce microbial contamination of food. In China, food safety has emerged as one of the country's most prominent domestic concerns, but there has been limited investment in surveillance, inter-agency coordination, outbreak investigation and data synthesis. After large outbreaks of Salmonella in the 1960s and E. coli O157:H7 in the 1990s, the United States transformed its approach to detecting and investigating foodborne infections, including deployment of a national, laboratory-based surveillance system that uses molecular subtyping. In China, the absence of a national, laboratory-based surveillance system means that it is difficult to rapidly detect a widely dispersed foodborne infection outbreak or the emergence of new foodborne infections. Based on lessons learned in the United States, we propose policy and administrative changes that China can adopt to strengthen detection and control of foodborne infections.
Global Public Health 12/2011; 7(7):766-78. · 0.92 Impact Factor
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Guang Xue He,
Hai Ying Wang,
Martien W Borgdorff,
Dick van Soolingen,
Marieke J van der Werf,
Zhi Min Liu,
Xue Zheng Li,
Hui Guo,
Yan Lin Zhao, Jay K Varma,
Christopher P Tostado,
Susan van den Hof
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ABSTRACT: We conducted a case-control study to investigate risk factors for multidrug-resistant tuberculosis (MDR TB) in the People's Republic of China. Genotyping analysis was used to estimate the percentage of cases from recent transmission among 100 MDR TB case-patients hospitalized during April 2007-July 2009. Molecular subtyping of isolates showed that 41% of MDR TB strains clustered. Beijing genotype was found in 94% of the MDR TB isolates and 79% of the pan-susceptible isolates. In multivariate analysis, MDR TB was independently associated with Beijing genotype, retreatment for TB, symptoms lasting >3 months before first evaluation at the hospital, lack of health insurance, and being a farmer (vs. being a student). MDR TB was associated with Beijing genotype and lower socioeconomic status. A large percentage of MDR TB cases seemed to result from recent transmission. Early detection, effective treatment, and infection control measures for MDR TB are needed to reduce transmission.
Emerging Infectious Diseases 10/2011; 17(10):1831-8. · 6.79 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 07/2011; 15(7):854. · 2.73 Impact Factor
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Lu Ran,
Shuyu Wu,
Yongjun Gao,
Xin Zhang,
Zijian Feng,
Zijun Wang,
Biao Kan,
John D Klena,
Danilo M A Lo Fo Wong,
Frederick J Angulo, Jay K Varma
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ABSTRACT: Foodborne infections are an important public health problem in China. In 2008, we conducted surveillance for laboratory-confirmed nontyphoidal Salmonella to monitor trends for this infection in China and to build capacity for rapid detection and response to foodborne outbreaks. Salmonella isolates from patients with diarrhea were sent from hospitals to local public health laboratories for confirmation, serotyping, and antimicrobial susceptibility testing. A total of 126 hospitals in 44 cities and counties from 8 provinces provided isolates and epidemiologic data for analysis. Of 23,140 stool specimens submitted to clinical laboratories, 662 (3%) grew Salmonella enterica. Salmonella were most commonly detected between April and October. The median age of infected patients was 27 years; 34% of infections occurred in patients <5 years old. Of the 662 isolates, we found 73 serotypes, of which serotype Enteritidis (31%) and serotype Typhimurium (26%) were the most common. The prevalence of resistance was high for clinically important antimicrobial agents, including ampicillin (41%) and ciprofloxacin (6%). More than 60% of isolates, including 35% of all Typhimurium, were resistant to three or more antimicrobial agents. In this first multiprovince surveillance report of laboratory-confirmed Salmonella infections in China, we found that Enteritidis and Typhimurium are the most common serotypes and that efforts to reduce antimicrobial resistance among Salmonella in China are needed. Although no outbreaks were detected using this system, efforts to improve this system's capacity to do so are underway.
Foodborne Pathogens and Disease 04/2011; 8(8):921-7. · 2.26 Impact Factor
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ABSTRACT: We describe four cases of Mycobacterium tuberculosis complex bacteremia diagnosed in immunocompetent neonates, who presented with high fever and/or jaundice within 72 h after Bacille Calmette-Guérin (BCG) vaccination. All neonates were hospitalized, and none received anti-mycobacterial therapy. All recovered completely and remain healthy 2-3.5 years later. Genotyping of one available isolate identified the pathogen as Mycobacterium bovis BCG. The similar clinical presentations and close temporal association between BCG vaccination and illness suggest that all four neonates likely had BCG bacteremia. BCG bacteremia shortly following vaccination among healthy neonates has not been previously described and merits further study to determine its frequency and clinical significance.
Vaccine 02/2011; 29(9):1727-30. · 3.77 Impact Factor
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ABSTRACT: Early detection of emerging infections in China is critical to the health of the 1.3 billion Chinese people and to the world. China's surveillance system for endemic infectious diseases has improved greatly since 2003, but the country's ability to conduct surveillance for laboratory-confirmed infections remains underdeveloped. This is dangerous for China, the world's most populous country, which has been the focus of global attention since outbreaks of severe acute respiratory syndrome (SARS) and avian influenza. We describe China's public health advances since the 2003 SARS outbreak and conclude that China must now invest far more in pathogen-based surveillance. An enhanced disease-detection system in China will help prevent and contain outbreaks before they cause substantial illness and death in China and other countries.
Health Affairs 01/2011; 30(1):127-35. · 4.31 Impact Factor
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Haileyesus Getahun,
Wanitchaya Kittikraisak,
Charles M Heilig,
Elizabeth L Corbett,
Helen Ayles,
Kevin P Cain,
Alison D Grant,
Gavin J Churchyard,
Michael Kimerling,
Sarita Shah,
Stephen D Lawn,
Robin Wood,
Gary Maartens,
Reuben Granich,
Anand A Date, Jay K Varma
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ABSTRACT: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.
We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%).
Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.
PLoS Medicine 01/2011; 8(1):e1000391. · 16.27 Impact Factor
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ABSTRACT: In resource-limited settings, abdominal ultrasound is often used to assist the diagnosis of tuberculosis (TB) in people with HIV (PLHIV), although data on performance characteristics are missing.
Cross-sectional study of PLHIV in Cambodia receiving a standardized TB diagnostic evaluation, including history, physical examination, chest radiography, microscopy and culture of various specimens, and abdominal ultrasound. Patients with at least one specimen culture positive for Mycobacterium tuberculosis were classified as having TB.
TB was diagnosed in 37 (18%) of 212 PLHIV. Abdominal ultrasound was abnormal in 15 of 37 (41%) patients with TB compared with 14 of 175 (8%) without TB (P < 0.01). Predictors of TB disease included multiple enlarged (1.2 cm or greater) abdominal lymph nodes on ultrasound (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 1.8-22.4), abnormal chest radiography (OR, 6.8; CI, 2.7-17.0), anorexia (OR, 4.6; CI, 1.8-11.7), and CD4 less than 200 cells/mm (OR, 3.3; CI, 1.2-9.1). Having multiple enlarged abdominal lymph nodes on ultrasound was 97.1% (CI, 93.5%-99.1%) specific for TB with a positive likelihood ratio of 11.4 (CI, 4.3-30.3).
Abdominal ultrasound is a useful diagnostic test for TB disease in PLHIV, increasing the posttest probability of TB when multiple enlarged abdominal lymph nodes are visualized. Its wider use may accelerate access to TB treatment, potentially reducing mortality in PLHIV.
JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2010; 55(4):500-2. · 4.43 Impact Factor
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Jay K Varma,
Kimberly D McCarthy,
Theerawit Tasaneeyapan,
Patama Monkongdee,
Michael E Kimerling,
Eng Buntheoun,
Delphine Sculier,
Chantary Keo,
Praphan Phanuphak,
Nipat Teeratakulpisarn,
Nibondh Udomsantisuk,
Nguyen H Dung,
Nguyen T N Lan,
Nguyen T B Yen,
Kevin P Cain
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ABSTRACT: 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.
Emerging Infectious Diseases 10/2010; 16(10):1569-75. · 6.79 Impact Factor
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Yang Huai,
Jinyan Lin, Jay K Varma,
Zhibin Peng,
Jianfeng He,
Chen Cheng,
Haojie Zhong,
Yuansheng Chen,
Yingdong Zheng,
Yuan Luo,
Wenjia Liang,
Xiaoling Wu,
Zhenyu Huang,
Jeffrey McFarland,
Zijian Feng,
Timothy M Uyeki,
Hongjie Yu
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ABSTRACT: We investigated the first known outbreak of pandemic 2009 influenza A (H1N1) at a primary school in China.
To describe epidemiologic findings, identify risk factors associated with 2009 H1N1 illness, and inform national policy including school outbreak control and surveillance strategies.
We conducted retrospective case finding by reviewing the school's absentee log and retrieving medical records. Enhanced surveillance was implemented by requiring physicians to report any influenza-like illness (ILI) cases to public health authorities. A case-control study was conducted to detect potential risk factors for 2009 H1N1 illness. A questionnaire was administered to 50 confirmed cases and 197 age-, gender-, and location-matched controls randomly selected from student and population registries.
The attack rate was 4% (50/1314), and children from all grades were affected. When compared with controls, confirmed cases were more likely to have been exposed to persons with respiratory illness either in the home or classroom within 7 days of symptom onset (OR, 4.5, 95% CI: 1.9-10.7). No cases reported travel or contact with persons who had traveled outside of the country.
Findings in this outbreak investigation, including risk of illness associated with contacting persons with respiratory illness, are consistent with those reported by others for seasonal influenza and 2009 H1N1 outbreaks in school. The outbreak confirmed that community-level transmission of 2009 H1N1 virus was occurring in China and helped lead to changes in the national pandemic policy from containment to mitigation.
Influenza and Other Respiratory Viruses 09/2010; 4(5):259-66. · 4.16 Impact Factor
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ABSTRACT: Drug resistance in malaria and in tuberculosis (TB) are major global health problems. Although the terms multidrug-resistant TB and extensively drug-resistant TB are precisely defined, the term multidrug resistance is often loosely used when discussing malaria. Recent declines in the clinical effectiveness of antimalarial drugs, including artemisinin-based combination therapy, have prompted the need to revise the definitions of and/or to recategorize antimalarial drug resistance to include extensively drug-resistant malaria. Applying precise case definitions to different levels of drug resistance in malaria and TB is useful for individual patient care and for public health.
Emerging Infectious Diseases 07/2010; 16(7):1063-7. · 6.79 Impact Factor
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Kevin P Cain,
Kimberly D McCarthy,
Charles M Heilig,
Patama Monkongdee,
Theerawit Tasaneeyapan,
Nong Kanara,
Michael E Kimerling,
Phalkun Chheng,
Sopheak Thai,
Borann Sar,
Praphan Phanuphak,
Nipat Teeratakulpisarn,
Nittaya Phanuphak,
Huy Dung Nguyen,
Thi Quy Hoang,
Hung Thai Le, Jay K Varma
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ABSTRACT: 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.
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.
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.
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.
New England Journal of Medicine 02/2010; 362(8):707-16. · 53.30 Impact Factor
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ABSTRACT: Over the past several years, new diagnostic techniques have been developed to allow for the rapid detection of multidrug resistant tuberculosis. The GenoType MTBDRplus test is a deoxyribonucleic acid (DNA) strip assay which uses polymerase chain reaction (PCR) and hybridization to detect genetic mutations in the genes that confer isoniazid (INH) and rifampn (RIF) resistance. This assay has demonstrated good performance and a rapid time to results, making this a promising tool to accelerate MDR-TB diagnosis and improve MDR-TB control. Validation of rapid tests for MDR-TB detection in different settings is needed to ensure acceptable performance, particularly in Asia, which has the largest number of MDR-TB cases in the world but only one previous report, in Vietnam, about the performance of the GenoType MDRplus assay. Thailand is ranked 18th of 22 "high-burden" TB countries in the world, and there is evidence to suggest that rates of MDR-TB are increasing in Thailand. We compared the performance of the GenoType MTBDRplus assay to Mycobacterial Growth Indicator Tube for Antimycobacterial Susceptibility Testing (MGIT AST) for detection INH resistance, RIF resistance, and MDR-TB in stored acid-fast bacilli (AFB)-positive sputum specimens and isolates at a Public TB laboratory in Bangkok, Thailand.
50 stored isolates and 164 stored AFB-positive sputum specimens were tested using both the MGIT AST and the GenoType MTBDRplus assay.
The GenoType MTBDRplus assay had a sensitivity of 95.3%, 100%, and 94.4% for INH resistance, RIF resistance, and MDR-TB, respectively. The difference in sensitivity between sputum specimens (93%) and isolates (100%) for INH resistance was not statistically significant (p = 0.08). Specificity was 100% for all resistance patterns and for both specimens and isolates. The laboratory processing time was a median of 25 days for MGIT AST and 5 days for the GenoType MTBDRplus (p < 0.01).
The GenoType MTBDRplus assay has been validated as a rapid and reliable first-line diagnostic test on AFB-positive sputum or MTB isolates for INH resistance, RIF resistance, and MDR-TB in Bangkok, Thailand. Further studies are needed to evaluate its impact on treatment outcome and the feasibility and cost associated with widespread implementation.
BMC Infectious Diseases 01/2010; 10:123. · 3.12 Impact Factor
