PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (911214)

Clipboard (0)
None

Related Articles

1.  CUTANEOUS TUBERCULOSIS: A 26-YEAR RETROSPECTIVE STUDY IN AN ENDEMIC AREA OF TUBERCULOSIS, VITÓRIA, ESPÍRITO SANTO, BRAZIL 
SUMMARY
Background:
Tuberculosis is a serious health problem in Brazil so that the knowledge on the aspects of cutaneous tuberculosis is medically important.
Objective:
To assess the characteristics of patients with cutaneous tuberculosis treated at the Cassiano Antonio Moraes University Hospital, located in the city of Vitória, State of Espírito Santo, Brazil.
Methods:
This is a retrospective, descriptive, observational and cross-sectional study using the medical records of 29 patients with cutaneous tuberculosis treated at the Dermatology and Pulmonology services of the hospital from 1986 to 2011. The inclusion criterion was the confirmation of cutaneous tuberculosis taking into account clinical, epidemiological, immunological, and bacteriological findings, as well as the response to specific treatment.
Results:
Of the 29 studied patients; 18 (62%) were women with average age of 37 years; the predominant clinical condition was erythema induratum of Bazin in 12 (41.4%) cases; and the cutaneous lesions were in the lower limbs in 19 (65.8%) patients. Extra-cutaneous involvement occurred in eight (27.6%) cases. The tuberculin tests were positive in 15 (79%) individuals and the assessment of the infectious agent was negative in most of the investigated cases.
Conclusion:
The study found a low frequency (0.44%) of cutaneous tuberculosis in an endemic area of tuberculosis. There was a predominance of infection in women aged thirty to forty years. Erythema induratum was the most common clinical condition, affecting mainly the lower limbs, in contrast to other Brazilian studies that found scrofuloderma as the most common manifestation, predominating in the cervical region of male children and adolescents.
doi:10.1590/S1678-9946201658049
PMCID: PMC4964318  PMID: 27410909
Tuberculosis; Cutaneous tuberculosis; Mycobacterium tuberculosis; Epidemiology; Tuberculid
2.  Delayed Diagnosis of Scrofuloderma Misdiagnosed as a Bacterial Abscess 
Annals of Dermatology  2012;24(1):70-73.
An 82-year-old woman presented with a four-month history of an ulcerative plaque overlying her left neck. This lesion had developed as a subcutaneous nodule, gradually increased in size, and evolved into ulcers. Before visiting our Dermatology clinic, the patient had been diagnosed as having a bacterial abscess, but treatments with antibiotics were unsuccessful. The presence of a purulent discharge and prominent ulceration caused further confusion as bacterial abscess, and radiologic evaluation on computed tomography also led to the possibilities of secondary lesions from an abscess or malignancy. However, the characteristic appearance of her lesion allowed us to discern cutaneous tuberculosis, especially scrofuloderma. Based on clinical examinations, staining for acid-fast bacilli, and positive findings of polymerase chain reaction, a quick diagnosis of scrofuloderma was made. After that, she was treated successfully with anti-tuberculosis therapy and the ulcer healed. Our case highlights the problem of delayed diagnosis of scrofuloderma presenting as a bacterial abscess. In conclusion, having a high index of suspicion is needed to diagnose cutaneous tuberculosis correctly.
doi:10.5021/ad.2012.24.1.70
PMCID: PMC3283855  PMID: 22363159
Bacterial abscess; Scrofuloderma
3.  258 A Novel Therapeutical Option in Resistant Ganglionar and Cutaneous Tuberculosis 
Background
Transfer factor was first described in 1955 and constitutes a Dialyzable Leukocyte Extract. It has been widely used in several infectious diseases and malignancies with satisfactory results. Although not yet fully clarified, among the mechanisms of action the most accepted is the enhancement of the cellular immunity.
Methods
We tested transfer factor in a 1 year old and 3 months patient diagnosed with Ganglionar Tuberculosis. 1 week after the administrarion of the Bacillus Calmette-Guérin vaccination, the present developed fever, cervical, submandibular, supraclavicular, inguinal and axillary lymphadenopathy. Later on the patient devoloped cutaneous clinical manifestations of tuberculosis such as scrofuloderma, fistulas, hypertrophic scars and ultimately, queloids. The patient had previously undergone short-term strictly supervised treatment for tuberculosis with very poor results. When the treatment was first administered, the patient had the following data: Total White Blood Count 12.9 Lymphocytes: 29% (12–46) CD3: 26.3% (59–90) T helper Cells (CD3/CD4) 21.6% (42–58) Cytotoxic T cells (CD3/CD8) 5.1% (17–33) Natural Killer Cells (CD56) 2.1% (3–7) B cells (CD19) 67.6 % (0–10).
Results
At the end of the treatment, the patient´s immune system was enhanced in terms of cell count and improval of skin manifestations. Total White Blood Count 6.5 Lymphocytes: 51.3% CD3: 48.5% T helper cells (CD3/CD4) 31.2% Cytotoxic T Cells (CD3/CD8) 14.6% Natural Killer cells (CD56) 12.2% B cells (CD19) 985%. Cicatrization process was improved, with involution of skin lesions os scrofuloderma and fistulas. Lymphadenopathy was no longer encountered. We have followed the patient for a year and half and no relapses have been encountered.
Conclusions
We consider Transfer Factor a valuable option as adyuvant therapy in cases of ganglionar and cutaneous tuberculosis refractory to conventional treatments. To our knowledge, this is the first report of a case of the disease treated satisfactorily with transfer factor.
doi:10.1097/01.WOX.0000412015.91855.71
PMCID: PMC3513134
4.  A Clinicopathological Study of Cutaneous Tuberculosis at Dibrugarh District, Assam 
Indian Journal of Dermatology  2012;57(1):63-65.
Background:
Cutaneous tuberculosis forms a small subset of extra pulmonary tuberculosis and has a worldwide distribution.
Aims:
The present study is an attempt to find out the incidence, clinical spectrum, and histopathological features of cutaneous tuberculosis.
Materials and Methods:
A total of 42 cases of newly diagnosed patients of cutaneous tuberculosis attending dermatology out patient department over a period of 1 year were included in the study. A detailed clinical examination and investigations including histopathological examination were carried out.
Results:
Scrofuloderma was the most common form seen in 50% cases followed by lupus vulgaris in 42.86%, tuberculosis verrucosa cutis in 4.76%, and lichen scrofulosorum in 2.38% cases. The Mantoux test was positive in 83.33% cases. Characteristic tuberculoid granulomas were seen in 72.22% cases of lupus vulgaris, 42.86% cases of scrofuloderma and all cases of tuberculosis verrucosa cutis and lichen scrofulosorum.
Conclusion:
Cutaneous tuberculosis is still highly prevalent in upper Assam. Early diagnosis and treatment are essential to prevent its complications.
doi:10.4103/0019-5154.92685
PMCID: PMC3312664  PMID: 22470216
Cutaneous tuberculosis; histopathology; granuloma
5.  Papulonecrotic Tuberculid with Scrofuloderma: An Uncommon Association 
Cutaneous tuberculosis can be classified as true cutaneous tuberculosis and tuberculids which is regarded as a hypersensitivity reaction to M. tuberculosis in patients with a high degree of tuberculin sensitivity. Papulonecrotic tuberculid (PNT) is a form of tuberculid. It is an uncommon manifestation even in areas with high prevalence of tuberculosis.
We report a case of 35-year-old man who presented with necrotizing papules in symmetrical fashion over the trunk and extremities for last one year along with a discharging sinus in right axilla for last two months. Papulonecrotic tuberculid (PNT) with scrofuloderma were suspected on clinical examination. Mantoux test was strongly positive with 20x20mm. He was treated successfully with ATT without any further appearance of new lesions.
doi:10.7860/JCDR/2015/10751.5524
PMCID: PMC4378789  PMID: 25859507
Cutaneous tuberculosis; Mantoux, M. tuberculosis; Necrotizing papules Varioliform scarring
6.  Vulval elephantiasis as a result of tubercular lymphadenitis: two case reports and a review of the literature 
Introduction
Elephantiasis as a result of chronic lymphedema is characterized by gross enlargement of the arms, legs or genitalia, and occurs due to a variety of obstructive diseases of the lymphatic system. Genital elephantiasis usually follows common filariasis and lymphogranuloma venereum. It may follow granuloma inguinale, carcinomas, lymph node dissection or irradiation and tuberculosis but this happens rarely. Vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis is very rare. We present two very unusual cases of vulval elephantiasis due to tuberculous destruction of the inguinal lymph nodes.
Case presentation
Two Indian women - one aged 40 years and the other aged 27 years, with progressively increasing vulval swellings over a period of five and four years respectively - presented to our hospital. In both cases, there was a significant history on presentation. Both women had previously taken a complete course of anti-tubercular treatment for generalized lymphadenopathy. The vulval swellings were extremely large: in the first case report, measuring 35 × 25 cm on the right side and 45 × 30 cm on the left side, weighing 20 lb and 16 lb respectively. Both cases were managed by surgical excision with reconstruction and the outcome was positive. Satisfactory results have been maintained during a follow-up period of six years in both cases.
Conclusions
Elephantiasis of the female genitalia is unusual and it has rarely been reported following tuberculosis. We report two cases of vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis, in order to highlight this very rare clinical scenario.
doi:10.1186/1752-1947-4-369
PMCID: PMC2994881  PMID: 21092075
7.  Glenohumeral tuberculous arthritis complicated with beta haemolytic streptococcus: An extraordinary rare association: A case report 
INTRODUCTION
Septic arthritis of the glenohumeral joint is a rare entity and its diagnosis is difficult with a superadded infection in the presence of underlying tuberculosis. We report the first case of group B beta haemolytic streptococcal glenohumeral arthritis with underlying tuberculosis.
CASE PRESENTATION
A 40 year old lady previously diagnosed to have poliomyelitis, rheumatoid arthritis, hepatitis C, and diabetes mellitus for the last 10 years, presented to the emergency room with diabetic ketoacidosis. Two weeks prior to presentation she developed fever along with pain and swelling in left shoulder with uncontrolled blood sugars. Local examination of the shoulder revealed global swelling with significant restricted range of motion. MRI showed a large multiloculated collection around the left shoulder joint extending into the axilla, and proximal arm. Urgent arthrotomy performed and about 120 ml thick pus was drained. The patient was started on clindamicin and antituberculous chemotherapy and her symptoms dramatically improved.
DISCUSSION
Bone and joint involvement accounts for approximately 2% of all reported cases of tuberculosis (TB), and it accounts for approximately 10% of the extra pulmonary cases of TB. Tuberculosis of the shoulder joint constitutes 1–10.5% of skeletal tuberculosis. Classical symptoms of fever, night sweats, and weight loss may be absent, and a concurrent pulmonary focus may not be evident in most cases.
CONCLUSION
Despite acute presentation of septic arthritis, in areas endemic for tuberculosis and particularly in an immunocompromised patient, workup for tuberculosis should be part of the routine evaluation.
doi:10.1016/j.ijscr.2011.09.008
PMCID: PMC3312055  PMID: 22382034
Glenohumeral tuberculous arthritis; Beta haemolytic streptococcus; Septic arthritis
8.  Efficacy of serum chitotriosidase activity in early treatment of patients with active tuberculosis and a negative sputum smear 
Background
The results of sputum culture for Mycobacterium tuberculosis must be awaited in most cases, which delays the start of treatment in patients with sputum smear-negative pulmonary tuberculosis. We investigated whether plasma chitotriosidase activity is a strong marker for early diagnosis of tuberculosis in patients for whom a bacillus smear is negative and tuberculosis culture is positive.
Methods
Clinical, radiological, and laboratory features were evaluated in 75 patients, 17 of whom were diagnosed as having active tuberculosis by negative acid-fast bacillus smear and positive culture, 38 as having sequel tuberculosis which was radiologically and microbiologically negative, and 20 who served as healthy controls. Serum chitotriosidase activity levels were measured in both cases and controls.
Results
The mean age of the cases with active pulmonary tuberculosis, cases with sequel lesions, and controls was 23 ± 2.4 years, 22 ± 1.7 years, and 24 ± 2.1 years, respectively. Serum chitotriosidase levels were 68.05 ± 72.61 nmol/hour/mL in smear-negative, culture-positive pulmonary tuberculosis cases (Group A) and 29.73 ± 20.55 nmol/hour/mL in smear-negative, culture-negative sequel pulmonary tuberculosis cases (Group B). Serum chitotriosidase levels from patients in Group A were significantly higher than in Group B and Group C. There was no statistically significant difference in serum chitotriosidase levels between cases with sequel pulmonary tuberculosis (Group B, smear-negative, culture-negative) and healthy controls (Group C).
Conclusion
In patients with active tuberculosis and a negative sputum smear for acid-fast bacillus, plasma chitotriosidase activity seems to be a strong marker for diagnosis of active disease which can be used while awaiting culture results.
doi:10.2147/TCRM.S31752
PMCID: PMC3431959  PMID: 22956876
pulmonary tuberculosis; serum chitotriosidase; diagnosis; antituberculous treatment; disease activity
9.  THE RELATION OF APICAL TUBERCULOSIS OF ADULTS TO THE FOCAL TUBERCULOSIS OF CHILDREN 
The age incidence of focal tuberculous lesions of the lungs demonstrates that they have their origin in most instances in childhood. Focal lesions which heal have been found at all ages after the 2nd year of life, but in more than half of all individuals these lesions are acquired between the ages of 10 and 18 years. In the period between 18 and 30 years at least 85 per cent of all individuals have 'acquired focal tuberculous lesions. The occurrence of tuberculous infection in the lungs, in regional lymphatic nodes, or in some other organs of the body such as the gastrointestinal tract and its lymphatic system, is nearly universal but doubtless a few individuals escape. That focal tuberculous lesions of the lung are occasionally acquired during adult life is shown by the slight increase in the proportion of those with these lesions as age increases from 18 years to old age. Apical lesions of the lung make their appearance in later childhood and occur with increasing frequency from adolescence to old age (50 per cent). After the 2nd year of life focal tuberculous lesions occurring in situations other than the apices of the lungs tend to heal and after the 10th year focal lesions are almost invariably encapsulated and latent or healed. Fatal tuberculosis after the 10th year is with few exceptions apical in origin. The apices are not only more susceptible to infection in later life but once infected afford less resistance to the extension of the lesion. The present series of cases has furnished opportunity to observe the character of the apical lesion in lungs of individuals previously infected with tuberculosis. With one exception the apical lesion (in eight instances) has pursued a chronic course and, encapsulated by fibrous tissue, has remained limited to the extreme apex of the lung. In one instance in a woman with advanced malignant disease chronic pulmonary tuberculosis has been progressive. Tuberculosis of the apices in those who have previously acquired a focal tuberculous lesion has pursued a chronic course and in most instances has remained latent or has completely healed. A very small group of instances of fatal pulmonary tuberculosis suggests that apical lesions in those who have not undergone previous infection may assume an unusually severe character. One instance of apical tuberculosis unaccompanied by focal lesions and followed by tuberculosis of the thoracic duct and disseminated miliary tuberculosis has been especially significant. Apical tuberculosis unaccompanied by evidence of preexisting tuberculosis may be accompanied by tuberculosis of the regional lymphatic nodes, whereas apical tuberculosis in an individual with a preexistent focal tuberculous lesion is not followed by tuberculosis of adjacent lymphatic nodes. It is well known that tuberculosis in previously uninfected animals is followed by tuberculosis of adjacent lymphatic nodes, whereas a second infection fails to implicate the regional lymphatic nodes. This relation has been well illustrated by the lungs of a monkey which acquired in confinement acute tuberculous pneumonia limited to the left lung; the lymphatic nodes on this side were greatly enlarged and caseous. The following observations indicate that apical tuberculosis of adults is not the result of infantile tuberculosis but is caused by subsequent infection: (a) Apical tuberculosis does not have its highest incidence, in accordance with common belief, in early adult life when focal infections acquired in childhood are relatively fresh and active but is more common in later life when the focal lesions of childhood have in most instances completely healed. It is noteworthy that most of these apical lesions of later life pursue a chronic course and are discovered at autopsy in individuals who have died from other causes. (b) The well characterized lesions of tuberculosis acquired in childhood and found in adults with apical lesions are almost invariably calcified and healed. The apical lesion is in most instances relatively fresh and caseous whereas the focal pulmonary lesion and associated lesions of regional lymphatic nodes exhibit no evidence of activity. (c) In a large proportion of instances of associated focal and apical tuberculosis the focal lesion is in one lung, whereas the apical lesion is limited to the opposite apex. This relation affords no support to the view that tuberculous lesions may be transmitted to the apex by way of the lymphatics.
PMCID: PMC2125652  PMID: 19868149
10.  Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia 
BMC Research Notes  2013;6:21.
Background
While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital.
Methods
A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression.
Result
A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31–40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection.
Conclusion
The prevalence of smear positive extra pulmonary tuberculosis infection in Gondar is high. Screening of lymph node and other body fluid specimens for extra pulmonary tuberculosis could help for treatment, control and prevention of the disease.
doi:10.1186/1756-0500-6-21
PMCID: PMC3558382  PMID: 23331864
Extra pulmonary tuberculosis; Acid fast bacilli; Northwest Ethiopia
11.  A Case of Extensive Multifocal Tuberculosis Verrucosa Cutis 
Tuberculosis is probably as old as the human race itself. Cutaneous tuberculosis constitutes a very small proportion of extra pulmonary tuberculosis. Extensive, multifocal involvement of cutaneous tuberculosis is a very rare manifestation. We report one such case of extensive, multifocal tuberculosis verrucosa cutis in a 30-year-old immunocompetent male patient in the absence of any primary tubercular focus.
doi:10.4103/0019-5154.135532
PMCID: PMC4103297  PMID: 25071280
Cutaneous tuberculosis; extensive; multifocal; tuberculosis verrucosa cutis
12.  MULTIFOCAL TUBERCULOSIS VERRUCOSA CUTIS 
Indian Journal of Dermatology  2011;56(3):332-334.
Tuberculosis has been a well-known affliction of human kind, since antiquity. Cutaneous tuberculosis constitutes only a small proportion of extra pulmonary tuberculosis and multifocal involvement of cutaneous tuberculosis is an even rarer manifestation. We report one such case of multifocal tuberculosis verrucosa cutis in a 17-year old male patient in the absence of any primary tuberculous focus.
doi:10.4103/0019-5154.82500
PMCID: PMC3132919  PMID: 21772603
Multifocal; cutaneous; tuberculosis
13.  The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study 
PLoS Medicine  2010;7(6):e1000296.
A postmortem study by Ted Cohen and colleagues reveals a huge toll of tuberculosis among patients dying in hospitals in KwaZulu-Natal, South Africa.
Background
Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis.
Methods and Findings
We studied a representative sample of 240 adult inpatients (aged 20–45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli.
Conclusions
Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly 10 million people develop tuberculosis—a contagious bacterial infection that affects the lungs and other parts of the body—and nearly two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis, which spreads in airborne droplets when people with the disease cough or sneeze. Its characteristic symptoms are a persistent cough, weight loss, and night sweats. Diagnostic tests for tuberculosis include the microscopic examination of sputum samples (mucus brought up from the lungs by coughing) for M. tuberculosis bacilli, and mycobacterial culture (in which bacteriologists try to grow M. tuberculosis from sputum or tissue samples). Although tuberculosis can be cured by taking several powerful antibiotics regularly for at least 6 months, global efforts to control tuberculosis are being thwarted by the emergence of strains of M. tuberculosis that are resistant to several antibiotics (multidrug and extensively drug-resistant tuberculosis) and by the HIV epidemic; people who are infected with HIV, the virus that causes AIDS, are particularly susceptible to tuberculosis because of their weakened immune system.
Why Was This Study Done?
In the past few years, tuberculosis has become the leading recorded cause of death in South Africa, a country where nearly a fifth of adults are infected with HIV. There are 122,000 recorded deaths from tuberculosis (including 94,000 deaths in HIV-positive people) in South Africa every year. However, because the accurate diagnosis of tuberculosis in HIV-positive people can be difficult—they are more likely to have sputum-negative tuberculosis than HIV-negative individuals—the true number of people dying because of tuberculosis is likely to be higher than the recorded number. Public-health experts in South Africa need an accurate picture of the tuberculosis deaths to help them improve tuberculosis control. In this postmortem study, the researchers determine the prevalence (the proportion of a population that has a disease) and drug sensitivity of tuberculosis among patients dying in a public hospital in KwaZulu-Natal, South Africa, to get a better estimate of how many people die because of tuberculosis in this setting.
What Did the Researchers Do and Find?
The researchers collected respiratory tract secretions and lung, liver, and spleen samples from 240 adults who died in the Edendale public hospital in KwaZulu-Natal over a 10-month period in 2008/9. They looked for M. tuberculosis bacilli in the samples, tried to culture M. tuberculosis from them, and tested any bacteria that grew for antibiotic sensitivity. They also collected information on current tuberculosis treatment status, previous tuberculosis treatment, and HIV status for each deceased patient (decedent) from medical records and from relatives. Ninety-four percent of the decedents were HIV positive and 50% had culture-positive tuberculosis at the time of death. Of the 50% of the decedents who were being treated for tuberculosis, 58% were culture positive at the time of death. A similar percentage (42%) of the decedents who were not being treated for tuberculosis were culture positive at the time of death. Seventeen percent of all the positive cultures were multidrug resistant and 16% of patients dying during their first course of tuberculosis treatment were infected with multidrug-resistant bacteria. Seventy percent of decedents who remained culture positive despite receiving tuberculosis treatment were infected with M. tuberculosis strains that were susceptible to all antibiotics.
What Do These Findings Mean?
These findings reveal the immense toll of tuberculosis among HIV-infected individuals in this hospital in KwaZulu-Natal. They show that many patients being treated for tuberculosis were culture positive at death despite being infected with antibiotic-sensitive M. tuberculosis, which suggests that diagnoses of tuberculosis are often made too late to alter the fatal course of infection. These findings also suggest that multidrug-resistant tuberculosis often goes undetected among HIV-infected individuals. Further studies are needed to confirm these findings elsewhere in South Africa and in other countries with a high HIV prevalence. Nevertheless, they suggest that public-health initiatives that improve the early diagnosis of tuberculosis, that introduce routine screening for tuberculosis among HIV-positive patients, and that accelerate the initiation of treatment for both tuberculosis and HIV might reduce the global death toll from tuberculosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000296.
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, on tuberculosis in South Africa, and on the Stop TB Partnership (some information is in several languages)
The US Centers for Disease Control and Prevention has information about tuberculosis and on tuberculosis and HIV coinfection
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
Information is available from Avert, an international AIDS charity, on tuberculosis and HIV
doi:10.1371/journal.pmed.1000296
PMCID: PMC2889914  PMID: 20582324
14.  A child presenting with tuberculous spondylitis in a single third cervical vertebra: a case report 
Introduction
Despite a global reduction in tuberculosis, extrapulmonary tuberculosis is increasing. Spinal tuberculosis remains the commonest form of skeletal tuberculosis. Cervical spine involvement is rare but is the most dangerous form because of diagnostic difficulties and serious residual disability. We report a child who had single vertebral involvement of her third cervical vertebra which is extremely rare. To the best of our knowledge isolated third cervical vertebra involvement in a child by tuberculosis has not been reported previously. Difficulties in obtaining material for histology and bacterial culture from this critical location and how the diagnosis was reached despite these challenges are highlighted.
Case presentation
A 10-year-old Sinhalese girl developed painful torticollis and ‘cries during sleep’. She had received Bacillus Calmette–Guérin vaccine at birth, was well nourished, and had no loss of weight, anorexia or contact with tuberculosis. A plain radiograph of her neck showed a collapsed third cervical vertebra with no disc involvement. Magnetic resonance imaging confirmed isolated destruction of third cervical vertebra associated with prevertebral soft tissue swelling indenting the thecal sac without cord compression. Her chest radiograph was normal. There was peripheral lymphocytosis, elevated erythrocyte sedimentation rate, negative tuberculin (Mantoux) test, and negative QuantiFERON®-TB GoldIn-Tube assay. Invasive procedures to obtain tissue for histology, smear or culture were perceived by parents as dangerous due to surrounding critical structures and consent was denied. The differential diagnosis included spinal tuberculosis and unifocal Langerhan cell histiocytosis. Nocturnal symptoms and the prevertebral collection of soft tissue (‘cold abscess’) were characteristic of tuberculosis, and nonspecific findings of elevated erythrocyte sedimentation rate and lymphocytosis supported this diagnosis. An incidental finding of a calcified hepatic nodule when evaluating for multifocal histiocytosis was presumed to be tuberculous because schistosomiasis and visceral leishmaniasis were extremely rare in her country of residence, Sri Lanka. Empirical treatment with a 12-month course of antitubercular therapy resulted in clinical recovery and radiological healing. There was no kyphosis or neurological sequel.
Conclusions
This report highlights to clinicians the value of a high index of suspicion and careful history taking in spinal tuberculosis; and how a combination of nonspecific findings helped reach a clinicoradiological diagnosis.
doi:10.1186/1752-1947-8-284
PMCID: PMC4147878  PMID: 25150548
Cervical tuberculosis; Single vertebra disease; Third cervical vertebra
15.  Cutaneous Tuberculosis : A Clinico-morphological Study 
Background
Cutaneous tuberculosis forms a small subset of extrapulmonary tuberculosis. The present study is an attempt to observe the clinico morphological pattern seen in cases of cutaneous tuberculosis over a period of 5 years, and to correlate them with mantoux reactivity and human immunodeficiency virus (HIV) status.
Methods
All cases of cutaneous tuberculosis observed among the dermatology in patients and those attending out patient department were included in the study. The basis of diagnosis was clinical, histopathological and microbiological. Intradermal mantoux test and serological test in the form of enzyme-linked immunosorbent assay (ELISA) for tuberculosis was done. HIV screening was carried out in 32 cases. CD4 counts were done in all HIV positive cases.
Results
A total 0.02% patient attending the dermatology centre had cutaneous tuberculosis. The spectrum of infection included 19 (51%) cases of lupus vulgaris, 7 (19%) cases of papulonecrotic tuberculids, six cases each of tuberculosis verrucosa cutis and scrofuloderma. One case had scrofuloderma and lupus vulgaris and another both scrofuloderma and papulonecrotic tuberculide. One case of lichen scrofulosorum was seen in a seven year old boy. 11 cases revealed evidence of systemic tuberculosis. Seven cases of HIV with CD4 counts between 50-500 cells/μl were observed in this study.
doi:10.1016/S0377-1237(06)80104-8
PMCID: PMC5034169  PMID: 27688538
Cutaneous tuberculosis; HIV status
16.  The Infectiousness of Tuberculosis Patients Coinfected with HIV 
PLoS Medicine  2008;5(9):e188.
Background
The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.
Methods and Findings
All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour.
Conclusions
A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.
Using a guinea pig detection system above an HIV-tuberculosis ward, Rod Escombe and colleagues found that most transmitted tuberculosis originated from patients with inadequately treated multidrug-resistant tuberculosis.
Editors' Summary
Background.
Every year, more than nine million people develop tuberculosis—a contagious infection usually of the lungs—and nearly two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis. These bacteria are spread in airborne droplets when people with the disease cough or sneeze. Most people infected with M. tuberculosis never become ill—their immune system contains the infection. However, the bacteria remain dormant within the body and can cause tuberculosis years later if host immunity declines. The symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Diagnostic tests for the disease include chest X-rays, the tuberculin skin test, and sputum cultures (in which bacteriologists try to grow M. tuberculosis from mucus brought up from the lungs by coughing). Tuberculosis can usually be cured by taking several powerful antibiotics daily for several months.
Why Was This Study Done?
Scientists performed definitive experiments on airborne tuberculosis transmission in the 1950s by exposing guinea pigs to the air from a tuberculosis ward. They found that a minority of patients actually transmit tuberculosis, that the infectiousness of transmitters varies greatly, and that effective antibiotic treatment decreases infectiousness. Since the 1950s, however, multidrug-resistant (MDR) and more recently extensively drug-resistant (XDR) strains of M. tuberculosis have become widespread. Treatment of drug-resistant tuberculosis is much more difficult than normal tuberculosis, requiring even more antibiotics, and for long periods, up to 2 years and beyond. In addition, HIV (the virus that causes AIDS) has emerged. HIV weakens the immune system so HIV-positive people are much more likely to develop active tuberculosis (and to die from the disease, which also speeds the development of HIV/AIDS) than people with a healthy immune system. Have these changes altered tuberculosis transmission between people? The answer to this question might help to optimize the control of tuberculosis infection, particularly in hospitals. In this study, the researchers investigate current patterns of tuberculosis infectiousness among HIV-positive patients by recreating the 1950s guinea pig model for tuberculosis transmission in a hospital in Lima, Perú.
What Did the Researchers Do and Find?
The researchers passed all the air from an HIV–tuberculosis ward over guinea pigs housed in an animal facility on the hospital's roof. The guinea pigs were tested monthly with tuberculin skin tests, and tissues from positive animals were examined for infection with M. tuberculosis. Sputum was also collected daily from the patients on the ward. The researchers then used the timing of patient admissions and guinea pig infections, together with the drug susceptibility patterns and DNA fingerprints of the M. tuberculosis strains isolated from the animals and the patients, to identify which patients had infected which guinea pigs. Finally, they used a mathematical equation to calculate the relative infectiousness of each patient in airborne infectious units (“quanta”) per hour. During the 505 study days, although 97 HIV-positive patients with tuberculosis were admitted to the ward, just ten patients were responsible for virtually all the characterized cases of tuberculosis among the guinea pigs. Six of these patients had MDR tuberculosis that had been suboptimally treated. The average patient infectiousness over the entire study period was 8.2 quanta per hour—six times greater than the average infectiousness recorded in the 1950s. Finally, the three most infectious patients (all of whom had suboptimally treated MDR tuberculosis) produced 226, 52, and 40 quanta per hour.
What Do These Findings Mean?
These findings show that a few inadequately treated HIV-positive patients with MDR tuberculosis caused nearly all the tuberculosis transmission to guinea pigs during this study. They also show for the first time that tuberculosis infectiousness among HIV-positive patients is very variable. The increase in the average patient infectiousness in this study compared to that seen in the 1950s hints at the possibility that HIV infection might increase tuberculosis infectiousness. However, studies that directly compare the tuberculosis infectiousness of HIV-positive and HIV-negative patients are needed to test this possibility. More importantly, this study demonstrates the potentially high infectiousness of inadequately treated MDR TB patients and their importance in ongoing TB transmission. These findings suggest that rapid, routine testing of antibiotic susceptibility should improve tuberculosis control by ensuring that patients with MDR TB are identified and treated effectively and quickly. Finally, they re-emphasize the importance of implementing environmental control measures (for example, adequate natural or mechanical ventilation of tuberculosis wards, or crowded waiting rooms or emergency departments where tuberculosis patients may be found) to prevent airborne tuberculosis transmission in health-care facilities, particularly in areas where many patients are HIV positive and/or where MDR tuberculosis is common.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050188.
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis, including multidrug-resistance tuberculosis, and on tuberculosis and HIV
The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about all aspects of tuberculosis (in English and Spanish)
The World Health Organization's 2008 report on global tuberculosis control—surveillance, planning, financing provides a snapshot of the current state of the global tuberculosis epidemic and links to information about all aspects of tuberculosis and its control (in several languages)
HIVInsite provides detailed information about coinfection with HIV and tuberculosis
• Avert, an international AIDS charity, also provides information about the interaction between HIV and tuberculosis
Tuberculosis Infection-Control in the Era of Expanding HIV Care and Treatment is a report from the World Health Organization
doi:10.1371/journal.pmed.0050188
PMCID: PMC2535657  PMID: 18798687
17.  Chronic Osteomyelitis of Humerus Presenting as Scrofuloderma 
Scrofuloderma is a common type of cutaneous tuberculosis usually manifests over an infected lymphnode, bone or joint that breaks down to form an undermined ulcer leading to discharging sinuses. We present a case of a 22 year old woman with diffuse swelling of right arm with overlying nodulo ulcerative skin lesions associated with seropurulent discharge. Routine investigations were normal and X-Ray of the right humerus showed the features of chronic osteomyelitis. Smears of the discharge for bacteria, fungi and acid fast bacilli were negative, but culture of skin biopsy showed Mycobacterium tuberculosis which was confirmed by PCR. Histopathology of skin biopsy showed epithelioid granulomatous inflammation suggestive of tuberculosis. After treating the patient with antitubercular therapy complete regression of the lesions occurred.
doi:10.4103/0019-5154.117344
PMCID: PMC3778807  PMID: 24082212
Osteomyelitis; scrofuloderma; tuberculosis
18.  LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis: A Multi-Country Cross-Sectional Evaluation 
PLoS Medicine  2011;8(7):e1001057.
This study, nested within a clinical trial, by Luis Cuevas and colleagues finds that LED-FM microscopy has higher sensitivity but lower specificity than Zn microscopy for detecting tuberculosis in sputum samples.
Background
The diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection.
Methods and Findings
Adults with cough ≥2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., “on the spot”) the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%–76.5%) and 65.8% (348/529, 95% CI 61.6%–69.8%) sensitive (p<0.001) and 90.9% (1,660/1,826, 95% CI 89.5%–92.2%) and 98% (1,790/1,826, 95% CI 97.3%–98.6%) specific (p<0.001). Using three LED-FM or three ZN smears per patient was 77% (408/529, 95% CI 73.3%–80.6%) and 70.5% (373/529, 95% CI 66.4%–74.4%, p<0.001) sensitive and 88.1% (95% CI 86.5%–89.6%) and 96.5% (95% CI 96.8%–98.2%, p<0.001) specific. The sensitivity/specificity of ZN smear microscopy and LED-FM did not vary between SMS and SSM.
Conclusions
LED-FM had higher sensitivity but, in this study, lower specificity than ZN smear microscopy for diagnosis of pulmonary TB. Performance was independent of the scheme used for collecting specimens. The introduction of LED-FM needs to be accompanied by appropriate training, quality management, and monitoring of performance in the field.
Trial Registration
Current Controlled Trials ISRCTN53339491
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Tuberculosis is a global public health problem. Every year, about 1.7 million people die from this contagious bacterial infection, and about 9 million new cases occur, mainly in low- and middle-income countries. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze, and usually infects the lungs (pulmonary tuberculosis). Symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Because tuberculosis is easily transmitted and potentially deadly, it is important that it is diagnosed quickly and accurately and immediately treated. The “gold standard” diagnostic test for tuberculosis is mycobacterial culture (in liquid or solid medium), in which laboratory technicians try to grow M. tuberculosis from sputum (mucus brought up from the lungs by coughing). However, this test is expensive, so most patients suspected of having pulmonary tuberculosis in resource-limited countries are investigated using sputum smear microscopy. In this cheaper but less sensitive test, sputum samples are “smeared” onto microscope slides, stained with Ziehl-Neelsen (ZN) dye, and then examined with a microscope for the presence of M. tuberculosis.
Why Was This Study Done?
With smear microscopy, multiple samples have to be examined to increase the test's sensitivity (the proportion of patients with culture-positive tuberculosis that the test detects). Because each smear examination takes up to 10 minutes, tuberculosis diagnosis with ZN smear microscopy creates a large laboratory workload. A variant form of smear microscopy—light-emitting-diode fluorescence microscopy (LED-FM)—could reduce this workload. With LED-FM, smears stained with a fluorescent dye can be examined in a quarter of the time it takes to examine ZN smears. In this study, the researchers evaluate the sensitivity and specificity (the proportion of people with a negative smear among people without tuberculosis; a high specificity indicates a low false-positive rate) of LED-FM using samples collected in a trial undertaken in four resource-limited countries (Ethiopia, Nepal, Nigeria, and Yemen) to investigate two schemes for sputum sample collection. In the spot-morning-spot (SMS) scheme, patients provide an on-the-spot specimen at their initial consultation, a specimen collected at home the next morning, and a second on-the-spot sample when they deliver their morning specimen. In the spot-spot-morning (SSM) scheme, patients provide two on-the-spot samples during their first clinic visit and a sample collected at home the next morning.
What Did the Researchers Do and Find?
In the main trial, the researchers collected sputum samples using the SMS or SSM scheme from 6,627 patients with a cough lasting more than two weeks. For their investigation of LED-FM, they examined nearly 2,400 samples (half SSM and half SMS specimens, about a quarter of which were tuberculosis culture-positive) with both ZN smear microscopy and LED-FM and determined the sensitivity and specificity of both tests—with one, two, or three sputum samples per patient—relative to mycobacterial solid culture. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. The sensitivities of two LED-FM and two ZN smears were 72.8% and 65.8%, respectively; the specificities of these tests were 90.9% and 98.0%. The sensitivities of three LED-FM and three ZN smears were 77% and 70.5%, respectively; the specificities of these tests were 88.1% and 96.5%. The sensitivity and specificity of both tests was similar for samples collected using the SMS and the SSM schemes.
What Do These Findings Mean?
These findings show that in the resource-limited countries included in this trial, LED-FM has a higher sensitivity but lower specificity than ZN smear microscopy. The researchers calculate that in this study the accuracy of three LED-FM examinations was 85% (2,017 out of 2,355 patients were correctly classified as infected or uninfected), whereas the accuracy of three ZN smears was 91.8%. Thus, although LED-FM should identify more people with tuberculosis than ZN smear microscopy, because of its lower specificity, its use might also lead to more people without tuberculosis being needlessly treated for the disease. Nevertheless, provided that the introduction of LED-FM is accompanied by appropriate training and performance monitoring, LED-FM is an attractive potential tool for the laboratory diagnosis of tuberculosis that, together with a move towards the collection of two on-the-spot smears in a single clinic visit, could ensure that poor patients have access to timely tuberculosis diagnosis and prompt treatment.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001057.
Details of the parent trial in which the samples used in this study were collected are available in a PLoS Medicine Research Article by Cuevas et al.
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis diagnostics; recent WHO policy statements on diagnosis of tuberculosis are available; the Stop TB Partnership provides information on global tuberculosis control (some information in several languages)
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
A new Web site dedicated to the discussion and optimization of smear microscopy has recently been launched
doi:10.1371/journal.pmed.1001057
PMCID: PMC3134458  PMID: 21765809
19.  Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients 
BMC Genomics  2013;14:404.
Background
Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15–20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored.
Results
The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain.
Conclusions
The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates.
doi:10.1186/1471-2164-14-404
PMCID: PMC3699378  PMID: 23773324
Extra-pulmonary Tuberculosis; Next-generation Sequencing; Genetic Heterogeneity; Single Nucleotide Variations; Insertion Elements; Phylogeny; Spoligotyping
20.  Impact of Replacing Smear Microscopy with Xpert MTB/RIF for Diagnosing Tuberculosis in Brazil: A Stepped-Wedge Cluster-Randomized Trial 
PLoS Medicine  2014;11(12):e1001766.
Betina Durovni and colleagues evaluated whether implementation of Xpert MTB/RIF increased the notification rate of laboratory-confirmed pulmonary tuberculosis and reduced the time to tuberculosis treatment initiation in 14 Brazilian primary care laboratories.
Please see later in the article for the Editors' Summary
Background
Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints).
Methods and Findings
We conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (p<0.001), resulting in an increased bacteriologically confirmed notification rate of 59% (95% CI = 31%, 88%). However, the overall notification rate did not increase (15%, 95% CI = −6%, 37%), and we observed no change in the notification rate for those without a test result (−3%, 95% CI = −37%, 30%). Median time to treatment decreased from 11.4 d (interquartile range [IQR] = 8.5–14.5) to 8.1 d (IQR = 5.4–9.3) (p = 0.04), although not among confirmed cases (median 7.5 [IQR = 4.9–10.0] versus 7.3 [IQR = 3.4–9.0], p = 0.51). Prevalence of rifampicin resistance detected by Xpert was 3.3% (95% CI = 2.4%, 4.3%) among new patients and 7.4% (95% CI = 4.3%, 11.7%) among retreatment patients, with a 98% (95% CI = 87%, 99%) positive predictive value compared to phenotypic drug susceptibility testing. Missing data in the information systems may have biased our primary endpoints. However, sensitivity analyses assessing the effects of missing data did not affect our results.
Conclusions
Replacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment.
Trial registration
ClinicalTrials.gov NCT01363765
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Tuberculosis—a contagious bacterial disease that usually infects the lungs—is a global public health problem. Each year, about 8.6 million people develop active tuberculosis and at least 1.3 million people die from the disease, mainly in resource-limited countries. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with active disease cough or sneeze. The characteristic symptoms of tuberculosis include cough, weight loss, and night sweats. Diagnostic tests for tuberculosis include sputum smear microscopy (microscopic analysis of mucus coughed up from the lungs), the growth (culture) of M. tuberculosis from sputum samples, and molecular tests (for example, the Xpert MTB/RIF test) that rapidly and accurately detect M. tuberculosis in sputum and determine its antibiotic resistance. Tuberculosis can be cured by taking several antibiotics daily for at least six months, although the emergence of multidrug-resistant tuberculosis is making the disease increasingly hard to treat.
Why Was This Study Done?
Quick, accurate diagnosis of active tuberculosis is essential to reduce the global tuberculosis burden, but in most high-burden settings diagnosis relies on sputum smear analysis, which fails to identify many infected people. Mycobacterial culture correctly identifies more infected people but is slow, costly, and rarely available in resource-limited settings. In late 2010, therefore, the World Health Organization recommended the routine use of the Xpert MTB/RIF assay (Xpert) for tuberculosis diagnosis, and several resource-limited countries are currently scaling up the use of Xpert in their national tuberculosis control programs. However, although Xpert works well in ideal conditions, little is known about its performance in routine (real-life) settings. In this pragmatic stepped-wedge cluster-randomized trial, the researchers assess the impact of replacing smear microscopy with Xpert for the diagnosis of tuberculosis in Brazil, an upper-middle-income country with a high tuberculosis burden. A pragmatic trial asks whether an intervention works under real-life conditions; a stepped-wedge cluster-randomized trial sequentially and randomly rolls out an intervention to groups (clusters) of people.
What Did the Researchers Do and Find?
The researchers randomly assigned 14 tuberculosis diagnosis laboratories in two cities to switch at different times from smear microscopy to Xpert for tuberculosis diagnosis. Specifically, at the start of the eight-month trial, all the laboratories used smear microscopy for tuberculosis diagnosis. At the end of each month, two laboratories switched to using Xpert, so that in the final month of the trial, all the laboratories were using Xpert. During the trial, 11,705 samples from patients with symptoms consistent with tuberculosis were examined using smear microscopy (baseline arm), and 12,522 samples were examined using Xpert (intervention arm). The researchers obtained the results of these tests from a database of all the diagnostic tests ordered in the Brazilian public laboratory system, and they obtained data on tuberculosis notifications during the trial period from the national notification system. In total, 9.7% and 14.2% of the tests in the baseline and intervention arm, respectively, were positive, and the laboratory-confirmed tuberculosis notification rate was 1.59 times higher in the Xpert arm than in the smear microscopy arm. However, the overall notification rate (which included people who began treatment on the basis of symptoms alone) did not increase during the trial. The time to treatment (the time between the laboratory test date and the notification date, when treatment usually starts in Brazil) was about 11 days and eight days in the smear microscopy and Xpert arms, respectively.
What Do These Findings Mean?
The findings indicate that, in a setting where laboratory diagnosis for tuberculosis was largely restricted to sputum smear examination, the implementation of Xpert increased the rates of laboratory-confirmed pulmonary (lung) tuberculosis notifications and reduced the time to treatment initiation, two endpoints of public health relevance. However, implementation of Xpert did not increase the overall notification rate of pulmonary tuberculosis (probably because of the high rate of empiric tuberculosis treatment in Brazil), although it did facilitate accurate and rapid detection of rifampicin resistance. The accuracy of these findings may be limited by certain aspects of the trial design, and further studies are needed to evaluate the possible effects of Xpert beyond diagnosis and the time to treatment initiation. Nevertheless, these findings suggest that replacing smear microscopy with Xpert has the potential to increase the confirmation (but not detection) of pulmonary tuberculosis and to reduce the time to treatment initiation at the population level in Brazil and other resource-limited countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001766.
The World Health Organization (WHO) provides information (in several languages) on tuberculosis, on tuberculosis diagnostics, and on the rollout of Xpert; further information about WHO's endorsement of Xpert is included in a Strategic and Technical Advisory Group for Tuberculosis report; the “Global Tuberculosis Report 2013” provides information about tuberculosis around the world, including Brazil
The Stop TB Partnership is working towards tuberculosis elimination and provides patient stories about tuberculosis (in English and Spanish); the Tuberculosis Vaccine Initiative (a not-for-profit organization) also provides personal stories about tuberculosis
The US Centers for Disease Control and Prevention provides information about tuberculosis and its diagnosis (in English and Spanish)
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
More information about this trial is available
doi:10.1371/journal.pmed.1001766
PMCID: PMC4260794  PMID: 25490549
21.  A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis 
PLoS Medicine  2011;8(7):e1000443.
Luis Cuevas and colleagues report findings from a multicenter diagnostic clinical trial in tuberculosis, showing that the sensitivity and specificity of a “front-loaded” diagnostic scheme is not inferior to that of a standard diagnostic scheme.
Background
More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out.
Methods and Findings
This clinical trial of adults with cough ≥2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected “on the spot” during the first visit plus one sputum sample collected the following morning (spot-spot-morning [SSM]) versus the standard spot-morning-spot (SMS) scheme. Analyses were per protocol analysis (PPA) and intention to treat (ITT). A sub-analysis compared just the first two smears of each scheme, spot-spot and spot-morning.
In total, 6,627 patients (3,052 SSM/3,575 SMS) were enrolled; 6,466 had culture and 1,526 were culture-positive. The sensitivity of SSM (ITT, 70.2%, 95% CI 66.5%–73.9%) was non-inferior to the sensitivity of SMS (PPA, 65.9%, 95% CI 62.3%–69.5%). Similarly, the specificity of SSM (ITT, 96.9%, 95% CI 93.2%–99.9%) was non-inferior to the specificity of SMS (ITT, 97.6%, 95% CI 94.0%–99.9%). The sensitivity of spot-spot (ITT, 63.6%, 95% CI 59.7%–67.5%) was also non-inferior to spot-morning (ITT, 64.8%, 95% CI 61.3%–68.3%), as the difference was within the selected −5% non-inferiority limit (difference ITT = 1.4%, 95% CI −3.7% to 6.6%). Patients screened using the SSM scheme were more likely to provide the first two specimens than patients screened with the SMS scheme (98% versus 94.2%, p<0.01). The PPA and ITT analysis resulted in similar results.
Conclusions
The sensitivity and specificity of SSM are non-inferior to those of SMS, with a higher proportion of patients submitting specimens. The scheme identifies most smear-positive patients on the first day of consultation.
Trial Registration
Current Controlled Trials ISRCTN53339491
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly 10 million people develop tuberculosis—a contagious bacterial infection that usually affects the lungs (pulmonary tuberculosis)—and about 1.7 million people die from the disease. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze. Thus, to control tuberculosis, it is essential that infected individuals are rapidly identified and treated. The “gold standard” diagnostic test for tuberculosis is mycobacterial culture, in which laboratory staff try to grow M. tuberculosis from sputum (mucus brought up from the lungs by coughing). However, although this test is sensitive (it detects most patients with tuberculosis) and has a high specificity (a low rate of false-positive results), it is too slow to produce results and too complex for routine use in the low- and middle-income countries where tuberculosis mainly occurs. In these countries, patients are usually investigated using direct sputum smear microscopy, a cheaper but less sensitive test in which multiple sputum samples treated with the acid-fast Ziehl-Neelsen stain are examined for the presence of M. tuberculosis bacilli.
Why Was This Study Done?
In most national tuberculosis control programs, patients provide an “on the spot” specimen during their initial consultation, a specimen collected at home the next morning, and another on-the-spot specimen when they bring their morning specimen to the clinic (a “spot-morning-spot,” or SMS, collection scheme). Unfortunately, patients often fail to return with their morning sample. Furthermore, the examination of three samples strains the limited laboratory resources of developing countries. Based on several recent reviews, the World Health Organization recently recommended that only two samples need be examined, a policy change that reduces the laboratory workload but does not avoid the problems of collecting a morning sample and patient drop-out during the diagnostic process. In this non-inferiority, cluster randomized trial, the researchers compare the sensitivity and specificity of a spot-spot-morning (SSM; two on-the-spot specimens collected during the first clinic visit an hour apart, and a third specimen collected at home the next morning) scheme for tuberculosis diagnosis with those of the standard SMS scheme. A non-inferiority trial investigates whether an intervention is not worse than a control intervention; a cluster randomized trial randomly assigns groups of patients rather than individual patients to the test and control interventions.
What Did the Researchers Do and Find?
The researchers enrolled 6,627 patients in Ethiopia, Nepal, Nigeria, and Yemen who had had a cough for more than two weeks (a characteristic symptom of tuberculosis). A quarter of the patients had culture-positive tuberculosis. The centers participating in the study were randomly assigned each week for a year to use either the SMS or the SSM sample collection scheme. Compared to mycobacterial culture, the sensitivities of the SSM and SMS schemes were 70.2% and 65.9%, respectively, which indicates that the new scheme was non-inferior to the SMS scheme. Similarly, the specificity of SSM (96.9%) was non-inferior to that of SMS (97.6%). Importantly, the sensitivity of diagnosis using just the first two samples collected in the SSM scheme was also non-inferior to the sensitivity of diagnosis using the first two samples collected in the SMS scheme (63.6% versus 64.8%; the researchers defined non-inferiority of SSM as a difference in its sensitivity compared to that of SMS of less than −5%). Finally, patients tested using the SSM scheme were more likely to provide the first two samples than patients tested using the SMS scheme (98% versus 94.2%).
What Do These Findings Mean?
These findings suggest that a sputum collection scheme in which two samples are collected one hour apart followed by a morning specimen could identify as many smear-positive patients as the standard SMS scheme. Importantly, they also indicate that examination of the first two specimens alone identifies most smear-positive patients independently of which scheme is used. These findings suggest that the SSM scheme might be more suitable for tuberculosis diagnosis than the SMS scheme in locations where patients are likely to drop out of the diagnosis process (for example, in low- and middle-income countries, where patients often live a long way from clinics). However, for an SSM scheme to work effectively, an on-site laboratory with a same-day turn-around service will be essential, and tuberculosis clinics will need to minimize contact between patients waiting to provide their second on-the-spot specimen.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000443.
A related PLoS Medicine Research Article by Cuevas et al. uses LED fluorescence microscopy for the diagnosis of pulmonary tuberculosis
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis diagnostics and on the recommendation to reduce the number of smears for diagnosis to two; the Stop TB Partnership provides information on global tuberculosis control (some information in several languages)
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
A new Web site dedicated to the discussion and optimization of smear microscopy has recently been launched
doi:10.1371/journal.pmed.1000443
PMCID: PMC3134460  PMID: 21765808
22.  Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis 
PLoS Medicine  2011;8(8):e1001062.
An up-to-date systematic review and meta-analysis by Karen Steingart and colleagues confirms that commercially available serological tests do not provide an accurate diagnosis of tuberculosis.
Background
Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries.
Methods and Findings
We used methods recommended by the Cochrane Collaboration and GRADE approach for rating quality of evidence. In a previous review, we searched multiple databases for papers published from 1 January 1990 to 30 May 2006, and in this update, we add additional papers published from that period until 29 June 2010. We prespecified subgroups to address heterogeneity and summarized test performance using bivariate random effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low- and middle-income countries) with 5,147 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For anda-TB IgG, the only test with enough studies for meta-analysis, pooled sensitivity was 76% (95% CI 63%–87%) in smear-positive (seven studies) and 59% (95% CI 10%–96%) in smear-negative (four studies) patients; pooled specificities were 92% (95% CI 74%–98%) and 91% (95% CI 79%–96%), respectively. Compared with ELISA (pooled sensitivity 60% [95% CI 6%–65%]; pooled specificity 98% [95% CI 96%–99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI 42%–64%) and comparable pooled specificity (98%, 95% CI 94%–99%). For extrapulmonary TB, we included 25 studies (40% from low- and middle-income countries) with 1,809 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of evidence was graded very low for studies of pulmonary and extrapulmonary TB.
Conclusions
Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low. These data informed a recently published World Health Organization policy statement against serological tests.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year nearly 10 million people develop tuberculosis—a contagious bacterial infection—and about two million people die from the disease. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze. It usually infects the lungs (pulmonary tuberculosis) but can also infect the lymph nodes, bones, and other tissues (extrapulmonary tuberculosis). The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Diagnostic tests for the disease include microscopic examination of sputum (mucus brought up from the lungs by coughing) for M. tuberculosis bacilli, chest radiography, mycobacterial culture (in which bacteriologists try to grow M. tuberculosis from sputum or tissue samples), and nucleic acid amplification tests (which detect the bacterium's genome in patient samples). Tuberculosis can usually be cured by taking several powerful drugs daily or several times a week for at least six months.
Why Was This Study Done?
Although efforts to control tuberculosis have advanced over the past decade, missed tuberculosis diagnoses and mismanaged tuberculosis continue to fuel the global epidemic. A missed diagnosis may lead to more severe illness and death, especially for people infected with both tuberculosis and HIV. Also, a missed diagnosis means that an untreated individual with pulmonary tuberculosis may remain infectious for longer, continuing to spread tuberculosis within the community Missed diagnoses are a particular problem in resource-limited countries where sputum microscopy and chest radiography often perform poorly and other diagnostic tests are too expensive and complex for routine use. Serological tests, which detect antibodies against M. tuberculosis in the blood (antibodies are proteins made by the immune system in response to infections), might provide a way to diagnose tuberculosis in resource-limited countries. Indeed, many serological tests for tuberculosis diagnosis are on sale in developing countries. However, because of doubts about the accuracy of these commercial tests, they are not recommended for use in routine practice. In this systematic review and meta-analysis, the researchers assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary tuberculosis. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers searched the literature for studies that evaluated serological tests for active tuberculosis published between 1990 and 2010. They used data from these studies to calculate each test's sensitivity (the proportion of patients with a positive serological test among patients with tuberculosis confirmed by a reference method; a high sensitivity indicates that the test detects most patients with tuberculosis) and specificity (the proportion of patients with a negative serological result among people without tuberculosis; a high specificity means the test gives few false-positive diagnoses). They also assessed the methodological quality of each study and rated the overall quality of the evidence. The researchers found 67 studies (half from low/middle-income countries) that evaluated serological tests for the diagnosis of pulmonary tuberculosis. The sensitivity of these tests varied between studies, ranging from 0% to 100%; their specificities ranged from 31% to 100%. For the anda-TB IgG test—the only test with sufficient studies for a meta-analysis—the pooled sensitivity from the relevant studies was 76% in smear-positive patients and 59% in smear-negative patients. The pooled specificities were 92% and 91%, respectively. The researchers found 25 studies (40% from low/middle-income countries) that evaluated serological tests for the diagnosis of extrapulmonary tuberculosis. Again, sensitivities and specificities for each test varied greatly between studies, ranging from 0% to 100% and 59% to 100%, respectively. Overall, for both pulmonary and extrapulmonary tuberculosis, the quality of evidence from the studies of the serological tests was graded very low.
What Do These Findings Mean?
This systematic review, which updates an analysis published in 2007, indicates that commercial serological tests do not provide an accurate diagnosis of tuberculosis. This finding confirms previous systematic reviews of the evidence, despite a recent expansion in the relevant literature. Moreover, the researchers' analysis indicates that the overall quality of the body of evidence on these tests remains poor. Many of the identified studies used unsatisfactory patient selection methods, for example. Clearly, there is a need for continued and improved research on existing serological tests and for research into new approaches to the serological diagnosis of tuberculosis. For now, though, based on these findings, cost-effectiveness data, and expert opinion, the World Health Organization has issued a recommendation against the use of currently available serological tests for the diagnosis of tuberculosis, while stressing the importance of continued research on these and other tests that could provide quick and accurate diagnosis of TB.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001062.
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis diagnostics on the Stop TB Partnership (some information is in several languages); the Strategic and Technical Advisory Group for Tuberculosis recommendations on tuberculosis diagnosis are available
The Web site Evidence-Based Tuberculosis Diagnosis (from Stop TB Partnership's New Diagnostics Working Group) provides access to several resources on TB diagnostics, including systematic reviews, guidelines, and training materials
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001062
PMCID: PMC3153457  PMID: 21857806
23.  Tuberculosis of the Breast: An Initial Presentation of the Metabolic Syndrome with Type 2 Diabetes Mellitus in a Young Nigerian Woman 
Breast tuberculosis is an uncommon presentation of extra pulmonary tuberculosis. A 40-year-old obese woman presented with a right breast abscess which had failed to heal after surgical drainage. There was no family history of breast disease. Biopsy and histology of the lesion showed chronic granulomatous inflammation with positive stains for acid fast bacilli compatible with tuberculosis. Further evaluation confirmed metabolic syndrome with type 2 diabetes mellitus. She was placed on antituberculosis chemotherapy and appropriate therapy for diabetes mellitus with complete resolution of the lesion. We report this case because of its rarity and to highlight the association between tuberculosis an infectious disease and overnutrition in diabetes mellitus, a noncommunicable disease.
doi:10.1155/2016/5485862
PMCID: PMC4806276  PMID: 27034859
24.  International Monetary Fund Programs and Tuberculosis Outcomes in Post-Communist Countries 
PLoS Medicine  2008;5(7):e143.
Background
Previous studies have indicated that International Monetary Fund (IMF) economic programs have influenced health-care infrastructure in recipient countries. The post-communist Eastern European and former Soviet Union countries experienced relatively similar political and economic changes over the past two decades, and participated in IMF programs of varying size and duration. We empirically examine how IMF programs related to changes in tuberculosis incidence, prevalence, and mortality rates among these countries.
Methods and Findings
We performed multivariate regression of two decades of tuberculosis incidence, prevalence, and mortality data against variables potentially influencing tuberculosis program outcomes in 21 post-communist countries for which comparative data are available. After correcting for confounding variables, as well as potential detection, selection, and ecological biases, we observed that participating in an IMF program was associated with increased tuberculosis incidence, prevalence, and mortality rates by 13.9%, 13.2%, and 16.6%, respectively. Each additional year of participation in an IMF program was associated with increased tuberculosis mortality rates by 4.1%, and each 1% increase in IMF lending was associated with increased tuberculosis mortality rates by 0.9%. On the other hand, we estimated a decrease in tuberculosis mortality rates of 30.7% (95% confidence interval, 18.3% to 49.5%) associated with exiting the IMF programs. IMF lending did not appear to be a response to worsened health outcomes; rather, it appeared to be a precipitant of such outcomes (Granger- and Sims-causality tests), even after controlling for potential political, socioeconomic, demographic, and health-related confounders. In contrast, non-IMF lending programs were connected with decreased tuberculosis mortality rates (−7.6%, 95% confidence interval, −1.0% to −14.1%). The associations observed between tuberculosis mortality and IMF programs were similar to those observed when evaluating the impact of IMF programs on tuberculosis incidence and prevalence. While IMF programs were connected with large reductions in generalized government expenditures, tuberculosis program coverage, and the number of physicians per capita, non-IMF lending programs were not significantly associated with these variables.
Conclusions
IMF economic reform programs are associated with significantly worsened tuberculosis incidence, prevalence, and mortality rates in post-communist Eastern European and former Soviet countries, independent of other political, socioeconomic, demographic, and health changes in these countries. Future research should attempt to examine how IMF programs may have related to other non-tuberculosis–related health outcomes.
David Stuckler and colleagues show that, in Eastern European and former Soviet Union countries, participation in International Monetary Fund economic programs have been associated with higher mortality rates from tuberculosis.
Editors' Summary
Background.
Tuberculosis—a contagious, bacterial infection—has killed large numbers of people throughout human history. Over the last century improvements in public health began to reduce the incidence (the number of new cases in the population in a given time), prevalence (the number of infected people), and mortality rate (number of people dying each year) of tuberculosis in several countries. Many authorities thought that tuberculosis had become a disease of the past. It has become increasingly clear, however, that regions impacted by health and economic changes since the 1980s have continued to face a high and sometimes increasing burden of tuberculosis. In order to boost funding and resources for combating the global tuberculosis problem, the United Nations has set a target of halting and reversing increases in global tuberculosis incidence by 2015 as one of its Millennium Development Goals. Yet one region of the world—Eastern Europe and the former Soviet Union—is not on track to achieve this goal.
Why Was This Study Done?
To achieve these targets, the World Health Organization (WHO) and tuberculosis physicians' groups promote the expansion of detection and treatment efforts against tuberculosis. But these efforts depend on the maintenance of good health infrastructure to fund and support health-care workers, clinics, and hospitals. In countries with significant financial limitations, the development and maintenance of these health system resources are often dependent upon international donations and financial lending. The International Monetary Fund (IMF) is a major source of capital for resource-deprived countries, but it is unclear whether its economic reform programs have positive or negative effects on health and health infrastructures in recipient countries. There are indications, for example, that recipient countries sometimes reduce their public-health spending to meet the economic targets set by the IMF as conditions for its loans. In this study, the researchers examine the relationship between participating in IMF lending programs of varying sizes and durations by 21 post-communist Central and Eastern European and former Soviet Union countries and changes in tuberculosis incidence, prevalence, and mortality in these countries during the past two decades.
What Did the Researchers Do and Find?
To examine how participation in IMF lending programs affected tuberculosis control in these countries, the researchers developed a series of statistical models that take into account other variables (for example, directly observed therapy programs, HIV rates, military conflict, and urbanization) that might have affected tuberculosis control. Participation in an IMF program, they report, was associated with increases in tuberculosis incidence, prevalence, and mortality rate of about 15%, which corresponds to hundreds of thousands of new cases and deaths in this region. Each additional year of participation increased tuberculosis mortality rates by 4.1%; increases in the size of the IMF loan also corresponded to greater tuberculosis mortality rates. Conversely, when countries left IMF programs, tuberculosis mortality rates dropped by roughly one-third. The authors' further statistical tests indicated that IMF lending was not a positive response to worsened tuberculosis control but precipitated this adverse outcome and that lending from non-IMF sources of funding was associated with decreases in tuberculosis mortality rates. Consistent with these results, IMF (but not non-IMF) programs were associated with reductions in government expenditures, tuberculosis program coverage, and the number of doctors per capita in each country. These findings associated with mortality were also found when analyzing tuberculosis incidence and prevalence data.
What Do These Findings Mean?
These findings indicate that IMF economic programs are associated with significantly worsened tuberculosis control in post-communist Central and Eastern European and former Soviet Union countries, independent of other political, health, and economic changes in these countries. Further research is needed to discover exactly which aspects of the IMF programs were associated with the adverse effects on tuberculosis control reported here and to see whether IMF loans have similar effects on tuberculosis control in other countries or on other non–tuberculosis-related health outcomes. For now, these results challenge the proposition that the forms of economic development promoted by the IMF necessarily improve public health. In particular, they put the onus on the IMF to critically evaluate the direct and indirect effects of its economic programs on public health.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050143.
This study is further discussed in a PLoS Medicine Perspective by Murray and King
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis, including a brief history of the disease
The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about tuberculosis
The World Health Organization provides information (in several languages) on efforts to reduce the global burden of tuberculosis, including information on the Stop TB Strategy and the 2008 report on global tuberculosis control—surveillance, planning, financing
Detailed information about the International Monetary Fund is available on its Web site
An article that asks “Does the IMF constrain health spending in poor countries?” (with a link to a response from the IMF) is provided by the Center for Global Development
doi:10.1371/journal.pmed.0050143
PMCID: PMC2488179  PMID: 18651786
25.  Tuberculous Otitis Media and Lupus Vulgaris of Face: An Unusual Association 
Tuberculous otitis media is a rare extra-pulmonary presentation of tuberculosis. Tuberculous otitis media is usually associated with pulmonary tuberculosis or tuberculosis involving nasopharynx and oropharynx. Lupus vulgaris is the most common morphological variant of cutaneous tuberculosis. The disease often affects the face and may be associated with nasal or nasopharyngeal tuberculosis. Lupus vulgaris associated with tuberculous otitis media is not reported in English literature. We report a case of 40 year old female patient who presented with symptoms of chronic suppurative otitis media and non-healing skin lesion of face. The biopsy of skin lesion showed granulomatous pathology and helped us to reach a diagnosis of tuberculous otitis media.
doi:10.1007/s12070-011-0202-1
PMCID: PMC3146669  PMID: 22754844
Chronic suppurative otitis media; Cutaneous tuberculosis; Tuberculous otitis media; Lupus vulgaris

Results 1-25 (911214)