Abdominal Tuberculosis: An Immigrant's Disease in the United States

Asserts that despite progress in controlling tuberculosis (TB), the decline in incidence has been disappointing, pointing to the need for new strategies and more effective tools. HIV/AIDS is one factor that challenges effective control of TB, especially in Southern African countries. Three key elements are needed to achieve effective TB control and to meet the Sustainable Development Goals: (1) early and accurate diagnosis and drug-sensitivity testing, (2) patient access to and completion of effective treatment, and (3) prevention of progression from latent infection to disease. Prevention requires vaccination and screening of individual at high risk as well as interventions such as air disinfection and the use of masks and respirators in hospitals and other congregate settings. Recommendations stress the need to strengthen health systems in high-burden countries by emphasizing community-based care over hospital care; to improve information systems to ensure patient adherence and manage medication supply chains; and to invest in research to develop the necessary interventions. Fundamentally, current global TB control strategies must undergo revision and receive significant research funding.

Introduction Abdominal tuberculosis (TB) is a common epitome of extrapulmonary TB (EPTB), wherein peritoneal and intestinal TB are the most prevalent forms. Diagnosis of abdominal TB is a daunting challenge owing to variable anatomical locations, paucibacillary nature of specimens and atypical clinical presentations that mimic other abdominal diseases, such as Crohn’s disease and malignancies. In this review, we made a comprehensive study on the diagnosis of abdominal TB. Area covered Various modalities employed for abdominal TB diagnosis include clinical features, imaging, bacteriological tests (smear/culture), histopathological/cytological observations, interferon-gamma release assays and nucleic acid amplification tests (NAATs). Among NAATs, loop-mediated isothermal amplification assay, PCR, multiplex-PCR, nested PCR, real-time PCR and GeneXpert® MTB/RIF were discussed. Identification of circulating Mycobacterium tuberculosis cell-free DNA by real-time PCR within ascitic fluids is another useful approach. Expert opinion Several novel molecular/immunological methods, such as GeneXpert Ultra, aptamer-linked immobilized sorbent assay, immuno-PCR (I-PCR) and nanoparticle-based I-PCR have recently been developed for detecting pulmonary TB and several EPTB types, which may also be explored for abdominal TB diagnosis. Precise and prompt diagnosis of abdominal TB may initiate an early therapy so as to reduce the complications, i.e. abdominal pain, ascites, abdominal distension, intestinal obstruction/perforation, etc., and avoid surgical involvement. Plain Language Summary Abdominal tuberculosis (TB) is a manifestation of extrapulmonary TB (EPTB), where peritoneal and intestinal TB are two major forms. Diagnosis of abdominal TB is difficult owing to low bacterial load present in clinical samples and non-specific clinical presentations as it mimics other diseases such as inflammatory bowel diseases, abdominal malignancies, etc. Bacteriological tests (smear/culture) almost fail owing to poor sensitivities and it is not always possible to get representative tissue samples for histopathological and cytological observations. In recent years, molecular tests i.e. nucleic acid amplification tests (NAATs), such as PCR/multiplex-PCR (M-PCR), nested PCR and GeneXpert are widely employed. Markedly, PCR/M-PCR and nested PCR exhibited reasonable good sensitivities/specificities, while GeneXpert revealed low sensitivity in most of the studies but high specificity, thus it could assist in differential diagnosis of intestinal TB and Crohn’s disease. Further, novel molecular/immunological tests employed for pulmonary TB and other EPTB types were described and those tests can also be utilized to diagnose abdominal TB. Reliable and rapid diagnosis of abdominal TB would initiate an early start of anti-tubercular therapy and reduce the severe complications.

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Current Concepts in the Management of Tuberculosis

Tuberculosis and human immunodeficiency virus co-infection in children: management challenges

46-Year-Old Man With Lower Back Pain

Introduction The HIV/AIDS pandemic has led to a rise in the incidence of tuberculosis and an epidemic of co-infection in many developing countries. Treatment of Mycobacterium tuberculosis in persons with HIV infection presents several challenges to the clinician, particularly in resource-poor countries. As will be discussed in this paper, diagnosis of latent tuberculosis relies on tuberculin skin testing, which has poor sensitivity and reproducibility in immunocompromised patients. The World Health Organization (WHO) recommends treatment of active tuberculosis as the primary means of global tuberculosis control. In practice, treatment of active tuberculosis typically requires that a symptomatic patient self-report to a health service for evaluation and management. Even if this approach to tuberculosis control were sufficient, many logistic and clinical problems remain involving tuberculosis diagnosis and therapy in the patient with HIV/AIDS. Recognizing the significant clinical and public health challenges surrounding the treatment of tuberculosis in patients with HIV infection, this paper will address a number of issues relevant to the care of co-infected patients. These include current guidelines for the treatment of active tuberculosis, as well as the diagnosis and treatment of latent tuberculosis in HIV-positive patients. The paper concludes with a discussion of promising new drugs for tuberculosis treatment. Epidemiology of tuberculosis and HIV co-infection It is estimated that one-third of the world population is infected with M. tuberculosis, the large majority of whom live in the developing world. The HIV pandemic of the past two decades has led to a rise in the incidence of tuberculosis, particularly in sub-Saharan Africa. There is now an emerging pandemic of patients with HIV infection who are co-infected with tuberculosis. As of December 2000, the WHO estimated that approximately 36.1 million persons worldwide are living with HIV and nearly one-third of these persons are co-infected with M. tuberculosis[1]. Approximately 68% of persons co-infected with HIV and tuberculosis live in sub-Saharan Africa, while 22% live in Southeast Asia. In the United States, the Centers for Disease Control and Prevention (CDC) estimates that approximately 40% of new tuberculosis cases among persons aged 15-44 years occur among individuals with HIV infection or AIDS. Tuberculosis rates among HIV-infected individuals in the United States, however, vary significantly among different groups, with highest rates among intravenous drug users and those who are foreign-born. Today, the burden of tuberculosis and HIV infections largely impacts the developing world, as well as the minority and low socio-economic individuals within industrialized countries. This paper will discuss issues in the treatment of M. tuberculosis in patients with HIV/AIDS; however, it is important to recognize that many patients co-infected with HIV and M. tuberculosis have limited or no access to essential diagnostic and therapeutic strategies. Escalating tuberculosis case rates over the past decade are largely attributable to HIV. Immunity to M. tuberculosis is partly under the control of the MHC class II restricted CD4 cells. With the progressive loss of CD4 cells, patients with HIV infection are at increased risk of reactivation of latent tuberculosis, as well as primary tuberculosis infection [2]. In turn, active tuberculosis infection appears to upregulate HIV replication, resulting in further immune compromise and accelerated HIV disease progression [3,4]. As a result, patients with HIV infection and active tuberculosis are at increased risk of opportunistic infections and associated mortality. The case fatality rate by the end of tuberculosis treatment is approximately 20% for new sputum smear-positive cases and up to 50% for new smear-negative cases [5]. Tuberculosis is the leading cause of death among persons with HIV/AIDS worldwide [6]. Guidelines for the treatment of active tuberculosis This section will review recent guidelines for the treatment of tuberculosis published by the Tuberculosis Committee of the Infectious Disease Society of America (IDSA) in conjunction with the American Thoracic Society (ATS) and the CDC [7,8]. In addition, we will review the Directly Observed Treatment Short-course (DOTS) strategy of the WHO for tuberculosis control worldwide. These published guidelines pertain to the treatment of tuberculosis without respect to the patient's HIV status. Modified recommendations for the treatment of tuberculosis in HIV-seropositive patients will be discussed in the following section. In April 2000, the IDSA published practice guidelines for the treatment of tuberculosis [7]. Table 1, adapted from the IDSA publication, lists the 10 essential recommendations for the treatment of patients with tuberculosis. Readers are referred to the original publication for detailed comments pertaining to these recommendations, as well as performance indicators. It should be noted that the IDSA recommendations were developed for use in industrialized nations such as the United States and are currently not feasible in many countries of the world. In Table 1, therefore, we have juxtaposed the WHO DOTS strategy guidelines for management of patients with tuberculosis.Table 1: Infectious Disease Society of America (IDSA) recommendations and World Health Organization Directly Observed Treatment Shortcourse (WHO DOTS) strategy for the management of patients with tuberculosis (TB).In geographic areas where ≥ 4% of the M. tuberculosis isolates are resistant to isoniazid, the IDSA, ATS, and CDC recommend that the usual three-drug regimen of isoniazid, rifampin and pyrazinamide be augmented with a fourth drug, either ethambutol or streptomycin. Clinicians will therefore need to be aware of the susceptibility patterns in their geographic area. In 1997, approximately 84% of the US population lived in states that had ≥ 4% of tuberculosis isolates resistant to isoniazid. Therefore, most patients in the United States should be started on an initial four-drug regimen. This is followed by isoniazid and rifampin for 18 weeks. Although a 6-month course of treatment is recommended, this should be extended to 9 months if there is a delay in AFB, culture conversion or clinical improvement for 8 weeks. The WHO Global Tuberculosis Programme (WHO/GTP) assists over 60 countries with national tuberculosis control and prevention. The priority of the WHO program has been active case finding and cure of infectious tuberculosis cases. In 1993, the WHO/GTP declared tuberculosis a global emergency and began promoting the DOTS strategy. The DOTS strategy consists of five key components: "1) Government commitment to sustained TB control activities; 2) Case detection by sputum smear microscopy among symptomatic patients self-reporting to health services; 3) Standardized treatment regimen of six to eight months for at least all confirmed sputum smear positive cases, with directly observed treatment (DOT) for at least the initial two months; 4) A regular, uninterrupted supply of all essential anti-tuberculosis drugs; and 5) A standardized recording and reporting system that allows assessment of treatment results for each patient and of the TB control programme performance overall" [9] (see Table 1). According to the WHO/GTP, as of 1999, 127 countries had accepted the DOTS strategy and were implementing it to varying degrees [10]. Nevertheless, the WHO/GTP estimate that, in 1999, only 45% of the world population had access to DOTS and 23% of new smear-positive cases were referred to DOTS programs. In addition, there are often a complex array of political, financial, and infrastructure problems that impede local DOTS programs. The current WHO DOTS strategy does not incorporate the diagnosis and treatment of latent tuberculosis. Some experts believe that the DOTS strategy, which focuses exclusively on the treatment of active cases, is insufficient for the control and elimination of tuberculosis, particularly in the HIV/AIDS era [11]. It has been recommended that targeted diagnosis and treatment of latent tuberculosis infection among specific populations be added to national tuberculosis control programs. At present, WHO recommends treatment of latent tuberculosis in HIV-positive patients; but only in settings where it is possible to provide HIV testing and counseling, and where it is possible to exclude cases of active tuberculosis and ensure proper follow-up. The DOTS strategy also employs empiric anti-tuberculous therapy without mycobacterial cultures and drug susceptibility testing. Without drug susceptibility information, it is impossible to identify cases of drug-resistant tuberculosis and to avoid treatment failure and further transmission of drug-resistant strains. The WHO recognizes the threat of multidrug-resistant tuberculosis (MDR-TB) and, in July 1999, convened a working group on DOTS-Plus for the treatment of MDR-TB [12]. DOTS-Plus is a pilot program to provide second-line drugs (i.e., fluoroquinolones, amikacin, kanamycin, capreomycin, cycloserine, para-aminosalicylic acid, and ethionamide) to manage MDR-TB in resource-limited countries. This strategy does not, however, address the role of mycobacterial cultures and drug susceptibility testing for individualized drug therapy and the prevention of drug-resistant tuberculosis. Finally, because DOTS relies on patients self-reporting to health services, additional tuberculosis transmission can take place before the patient is evaluated and receives appropriate therapy. Modeling of the tuberculosis epidemic in Tanzania suggests that DOTS may slow the incidence rate, but in the face of the HIV epidemic is unlikely to reverse the upward trend [13]. Again, some experts advocate targeted case finding, particularly among high-risk groups [11,14]. Diagnosis and treatment of active tuberculosis infection in patients with HIV infection This section deals specifically with the treatment of active tuberculosis in HIV-infected individuals as recommended by the CDC [15,16]. Again, many people co-infected with HIV and tuberculosis in the developing world do not have access to the relevant diagnostic tests and anti-tuberculosis and antiretroviral therapies. To impact tuberculosis-associated morbidity and mortality worldwide, developing countries will require both the skills and commodities to diagnose and treat individuals effectively. At present, tuberculosis treatment for the HIV-positive patient as recommended by the CDC is not applicable in most resource-poor countries. Treatment of active and latent tuberculosis infection in patients with HIV depends on the application of both clinical judgment and appropriate diagnostic tests. Active tuberculosis can occur at any CD4 cell count but atypical presentations are more likely with advanced HIV disease or AIDS. Clinicians should be alert to the sometimes atypical presentations of pulmonary and extrapulmonary tuberculosis in HIV-infected patients. Sputum acid fast staining, mycobacterial cultures, and drug susceptibility testing are recommended in all patients suspected of having tuberculosis. However, patients with HIV are slightly less likely to have positive sputum smears than non-HIV-infected individuals [17]. Likewise, chest radiographic findings can vary depending on the degree of immunosuppression. Patients with CD4 cell counts greater than 200 are more likely to have classic findings of upper lobe infiltrates with cavitary lesions, while those patients with AIDS may more likely have hilar adenopathy and pleural effusions without cavitations [18]. Mycobacteremia and extrapulmonary tuberculosis, especially meningitis and adenopathy, also correlate with diminishing numbers of CD4 cells and degree of immunosuppression. Thus, for patients with HIV infection, the diagnosis of active tuberculosis is more challenging. Clinical suspicion of tuberculosis in a patient known or suspected of being HIV-infected should result in prompt initiation of anti-tuberculosis therapy regardless of sputum staining or radiograph findings. The 1998 CDC recommendations for the treatment of tuberculosis among patients infected with HIV are summarized in Table 2[15]. The treatment of tuberculosis in the HIV-seropositive patient may differ from the standard treatment in the following ways: (i) choice of anti-tubercular regimen and dose adjustments; (ii) duration of treatment (ideally with directly observed therapy); (iii) promotion of antiretroviral therapy; and (iv) monitoring requirements. Due to rapid advances in the management of HIV disease, it is recommended that all patients co-infected with HIV and tuberculosis should be evaluated by a specialist to ensure optimal management.Table 2: Tuberculosis (TB) treatment recommendations for the HIV-seropositive patient.The treatment algorithm begins with establishing the patient's HIV status and whether the patient is on optimal antiretroviral therapy. All patients diagnosed with active tuberculosis should be HIV tested and, if seropositive, evaluated for antiretroviral therapy. It was previously felt that the diagnosis of active tuberculosis should result in the deferral of antiretroviral therapy. Early initiation of antiretroviral therapy is now recommended. While being treated for tuberculosis, the HIV-positive patient not receiving concurrent HIV therapy should be reassessed every 3 months for initiation of antiretroviral therapy. Known or suspected HIV-positive patients should receive prompt initiation of effective anti-tuberculosis therapy. If antiretroviral therapy is not started, the patient can typically receive standard anti-tuberculosis therapy: isoniazid, rifampin, pyrazinamide, and ethambutol. If the patient is to receive simultaneous anti-tuberculosis and antiretroviral therapy, the selected regimens and doses must account for significant drug-drug interactions between the rifamycins (rifampin, rifabutin, rifapentine) and the protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTI). Rifamycins, particularly rifampin, induce the hepatic cytochrome P-450 (CYP450) and reduce the serum levels of protease inhibitors, NNRTI, and other drugs metabolized by the CYP450 system. The CDC generally recommends the substitution of rifabutin, a less potent CYP450 inducer, for rifampin to allow simultaneous use of protease inhibitors and NNRTI. The use of rifampin with protease inhibitors or NNRTI is contraindicated, except in three antiretroviral combinations: (i) the NNRTI efavirenz and two nucleoside reverse transcriptase inhibitors (NRTI); (ii) the protease inhibitor ritonavir and one or more NRTI; and (iii) the combination of ritonavir and saquinavir, either hard-gel or soft-gel capsules [16]. Table 3 lists the recommended anti-tubercular drug doses, depending on frequency of administration and concurrent antiretroviral use.Table 3: Anti-tubercular drug doses.If the HIV-positive patient is already on an effective anti-retroviral regimen at the time of tuberculosis diagnosis, it is desirable to continue the patient on the same antiretroviral regimen with appropriate dose adjustments. If the patient is starting a new antiretroviral regimen, options include: (i) a rifabutin-based regimen with the necessary protease inhibitor or NNRTI dose adjustments; (ii) a non-rifamycin-containing regimen such as isoniazid, streptomycin, pyrazinamide, ethambutol for 2 months, then isoniazid, streptomycin, ethambutol for 7 months; or (iii) a regimen that does not contain a protease inhibitor or NNRTI. Table 4 lists the recommended dose adjustments for rifabutin-based regimens. Given the complexity of these drug interactions, it is recommended that the selection of dual anti-tubercular and antiretroviral therapies be made following consultation with a specialist.Table 4: Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) dose adjustments with rifabutin.Among the protease inhibitors, ritonavir has the highest potency in inhibiting the CYP450 pathway. With any dose of ritonavir, including low-dose ritonavir 100 mg twice a day, a reduced dose of rifabutin (150 mg two or three times per week) is recommended. According to the 2000 CDC guidelines for the use of rifabutin or rifampin among patients taking protease inhibitors or NNRTI, co-administration of ritonavir with the usual dose of rifampin (600 mg daily or two or three times per week) may be an option but pharmokinetic and clinical data are limited [16]. As previously stated, a patient taking the combination of saquinavir (either the soft-gel or hard-gel capsule) and ritonavir should take the reduced dose of rifabutin (150 mg two or three times per week). The saquinavir-ritonavir combination may possibly be given with the usual dose of rifampin but, again, limited pharmacokinetic and clinical data are available. Saquinavir, as a sole protease inhibitor, is generally not recommended in combination with rifabutin because the serum levels of saquinavir may be decreased as much as 45%. Indinavir, nelfinavir, and amprenavir should not be used in combination with rifampin, but all three protease inhibitors can be administered with a reduced daily dose of rifabutin (150 mg daily) or the usual dose of rifabutin (300 mg two or three times per week). Efavirenz induces CYP450 and accelerates rifamycin metabolism; therefore, efavirenz should be co-administered with an increased dose of rifabutin (450 or 600 mg daily, or 600 mg two or three times per week). According to the recent CDC guidelines, efavirenz may be combined with the usual dose of rifampin (600 mg daily or two or three times per week). The NNRTI nevirapine should typically be given with the usual dose of rifabutin (300 mg daily or two or three times per week). If co-administration of nevirapine with rifampin is clearly indicated, careful monitoring is recommended. The use of delavirdine is contraindicated during the treatment of tuberculosis because the drug levels are markedly decreased with both rifampin and rifabutin. HIV-infected patients have a higher incidence of drug-resistant tuberculosis isolates than non-HIV-infected patients. There have been several reports of increased risk of rifampin resistance among HIV-positive patients [19-21]. Higher rates of drug-resistant tuberculosis in HIV-infected patients may be associated with biological, behavioral, and societal factors including drug malabsorption, non-adherence, nosocomial outbreaks, and inadequate drug therapy in countries with high rates of co-infection. Directly observed therapy, regarded as the best strategy for ensuring adherence and limiting drug-resistant tuberculosis, is recommended for all patients with HIV infection [15]. In a randomized, controlled trial of anti-tuberculosis therapy among HIV-positive patients in Baltimore, Maryland, patients who received supervised therapy for tuberculosis had better survival than those who self-administered therapy [22]. Treatment of drug-resistant tuberculosis involves initiation of a multi-drug regimen tailored to the susceptibility profile of the organism. Due to the diversity of resistance patterns, it is not possible to recommend standardized protocols for therapy. Any regimen should include two or more drugs to which the isolate is susceptible. For HIV-positive patients at risk of MDR-TB, defined as resistance to both isoniazid and rifampin, initial empiric treatment should include second-line tuberculosis drugs to which resistance is uncommon. The 1999 WHO Essential Drug List was to include the following second-line tuberculosis amikacin, kanamycin, capreomycin, cycloserine, acid, and and drug susceptibility testing should be on all tuberculosis isolates and the anti-tuberculosis regimens Although MDR-TB is associated with a high mortality rate especially in resource-poor countries where the detection of drug resistance to months, if at and the second-line drugs are often months is the duration of treatment for pulmonary tuberculosis among HIV-positive patients in the United States a regimen is used [15]. treatment is for patients with a clinical or conversion of sputum cultures from positive to Some experts recommend the use of treatment regimens in all patients with HIV infection, especially among patients with advanced [17]. duration of treatment is clearly recommended in patients with slow clinical or with or HIV-positive individuals with active tuberculosis to be at increased risk of tuberculosis of a 6-month regimen. A trial of isoniazid was among HIV-positive patients in who a 6-month regimen of isoniazid decreased the risk of a of tuberculosis among HIV-positive patients. This not whether these were to M. tuberculosis or both of which have previously been The recommend of isoniazid for HIV-positive patients of tuberculosis therapy. At present, the WHO and the CDC recommend a months of directly observed tuberculosis therapy without Treatment of latent tuberculosis infection in patients with HIV infection It is estimated that 2 people worldwide are infected with latent tuberculosis. Patients with HIV infection are at increased risk of to active disease [2]. In 2000, the and the CDC new guidelines for the diagnosis and treatment of latent tuberculosis infection This public health strategy both prevention by the latent infection before it to active infection and primary prevention by further tuberculosis In addition, the use of active antiretroviral therapy has been to reduce the incidence of tuberculosis among persons with HIV infection The new guidelines recommend targeted of populations and patients at increased risk of tuberculosis infection who from treatment to active for targeted include drug health care of and all patients with HIV Diagnosis of latent tuberculosis infection is on the tuberculin skin new including detection are being developed A has with tuberculin skin testing in are to the diagnostic of this in the United States and in populations with varying degrees of risk for latent tuberculosis. There be two significant of developing tests for the detection of latent M. tuberculosis tests the need for a health service at and their be less than tuberculin skin testing. of latent tuberculosis in an HIV-infected patient can be a diagnostic It has been that the sensitivity of tuberculin skin testing may be in patients with to as well as to and can in persons with HIV infection and of the is associated with higher CD4 cell For these testing is no recommended for the diagnosis of latent tuberculosis. guidelines are to treat latent tuberculosis infection in HIV-infected persons with at high-risk of latent tuberculosis or with recent to a case of active tuberculosis should receive therapy regardless of tuberculin has been the of treatment of latent tuberculosis clinical have a in the risk of to active tuberculosis following months of isoniazid therapy. The optimal duration of isoniazid therapy has also been including the trial of the Tuberculosis and in in the and this or months of isoniazid therapy months of isoniazid therapy reduced the tuberculosis incidence by with for months and 20% for 3 months; however, with months therapy was than for of therapy A recent of isoniazid therapy in that from isoniazid therapy 9 months, with no additional associated with therapy The new and CDC guidelines recommend isoniazid therapy for 9 months (300 mg isoniazid daily mg with months of therapy as a less The to isoniazid therapy include and poor Directly observed therapy has been to adherence but is not important in the treatment of latent tuberculosis has been the of regimens that may adherence and reduce have the of regimens for the treatment of latent tuberculosis in individuals A trial that daily rifampin and pyrazinamide for 2 months was to isoniazid for months for the treatment of latent tuberculosis in HIV-infected persons the of these the new guidelines regimens for the treatment of latent tuberculosis as summarized in Table from their publication rifampin and pyrazinamide for 2 months (600 mg rifampin daily pyrazinamide daily) is the regimen for HIV-infected patients and be for suspected cases of tuberculosis. should be for rifampin in patients receiving protease inhibitors or NNRTI, further is to in the treatment of latent tuberculosis. The same drug-drug interactions and dose adjustments for antiretroviral drugs and rifamycins It is that the also recommends the regimen for individuals the the clinical for this combination have been only in HIV-positive patients. If MDR-TB is the recommended therapy is pyrazinamide and ethambutol or pyrazinamide and a (i.e., or for Treatment for suspected to MDR-TB should be extended to months for HIV-positive American Thoracic Society and Centers for Disease Control and Prevention guidelines for the treatment of latent tuberculosis the use of rifampin pyrazinamide therapy in infected patients has been associated with a rate of patients with resulting from the use of therapy have been to the five of these patients on these CDC and have their 2000 recommendations The (i) that be used with particularly in patients with disease, on or those taking drugs; and (ii) that patients who are treated with be by a health care at and for a of tests and evaluation with a at 8 to treatment therapy with the regimen should be for significant rates of have not been observed in HIV-infected patients treated with this regimen, either in clinical or to the use of the regimen in For HIV-infected patients to persons with active tuberculosis, treatment for latent tuberculosis should be a tuberculin In addition, some experts advocate HIV-infected individuals who in high-risk evaluation for latent tuberculosis treatment should include a careful and and, chest radiograph to exclude active tuberculosis. anti-tubercular drugs in treatment of tuberculosis, particularly for MDR-TB, will on the of new anti-tubercular there are several drugs under that have in M. tuberculosis. In some cases the drug has also in a of tuberculosis, and some have received and Drug for other under include and other and is a rifamycin the serum of which is three times than that of the rifampin The of M. tuberculosis is to or one to that of Given the between and other rifamycin the of over rifampin pharmokinetic In the infected with tuberculosis and in tuberculosis a regimen is less active than a daily regimen, both rifamycins being given at 10 In tuberculosis however, the regimen is significantly less active than the daily regimen In the regimens during the of tuberculosis therapy may provide increased to as well as to health care programs. is an for and other infections that has in M. tuberculosis, to that of and in in a of tuberculosis that at 100 is as as isoniazid at and more than clinical are being to the role of in combination therapy active tuberculosis. and also promising in a of tuberculosis are a class of inhibitors with and The of at 100 is with isoniazid at per an by the and Drug for the treatment of appears to be less active M. tuberculosis than It has been recommended, however, for further at higher is a new to that has been to potent in M. in were also to be to this with of In a administration of this drug at a dose of per led to of disease burden in and with that with isoniazid per and issues in the treatment of tuberculosis in patients with HIV have previously to some of the and issues that the treatment of tuberculosis in resource-poor countries. At the and there may also some important and to effective tuberculosis treatment. A among tuberculosis patients in Tanzania that only of the patients had of the disease and treatment In a recent from people were generally well HIV but tuberculosis of and were to AIDS than tuberculosis. patients with tuberculosis were often as having AIDS. Due to the associated with the that patients with tuberculosis may not or to appropriate These the important impact that the HIV epidemic may have on the public and to tuberculosis. a epidemic of tuberculosis and HIV co-infection in many of the developing world. The increased of tuberculosis and HIV/AIDS and the rise of MDR-TB a health threat to all While significant have been made in developing regimens for the treatment of active and latent tuberculosis, therapy is and second-line drugs are drug resistance is for are the anti-tuberculosis of drugs such as and and the of which may treatment. The optimal use of these drugs in combination therapy is a promising of active In addition, we advocate the of new and tuberculosis drugs that will be made to patients in developing countries.

Dealing With Threat of Drug-Resistant Tuberculosis: Background Information for Interpreting the Andrew Speaker and Related Cases

Tuberculosis (TB) is an important infectious disease worldwide. Classical spinal TB has specific radiological findings involving adjacent vertebral bodies with destruction of the intervertebral disc and involvement of paravertebral soft tissues with cold abscess formation. However, a few cases not exhibiting the radiological characteristics of TB spondylitis have been reported. We report a rare case of lumbar spinal TB with atypical clinical and radiological presentations that was difficult to differentiate from a malignant spinal tumor. A 21-year-old man, who had immigrated to Japan from the Philippines 5 years ago, without a significant medical history, presented with back pain lasting 1 month and progression of gait disturbance 2 weeks prior to presentation. Laboratory tests showed normal blood cell counts and normal value of C-reactive protein levels. Preoperative imaging studies indicated a possible spinal tumor. However, histopathologic findings of the epidural soft tissues at the first surgery led to the diagnosis of spinal mycobacterial infection. The diagnosis of spinal TB was confirmed by a positive culture of Mycobacterium tuberculosis obtained at the second surgery. Given the progressive nature of neurologic deterioration, instead of needle biopsy, we proceeded with surgical intervention 8 days after admission; simultaneous neural decompression and open biopsy. Histological findings of the excised epidural soft tissues led to the diagnosis of spinal mycobacterial infection. We performed the second surgery involving additional resection of epidural soft tissues for further dural decompression and to obtain specimens for mycobacterial culture. Immediately after the second surgery, the patient commenced combination therapy with anti-tuberculous drugs. The patient demonstrated significant recovery of motor function in the lower extremities, and was able to run at 2 months after the second surgery. The epidural granulomas completely disappeared on magnetic resonance imaging 3 months postoperatively. Atypical clinical and radiological presentations of spinal TB present a challenge for appropriate diagnosis and early treatment. Even in developed countries where there are very few spinal TB patients, clinicians should be aware that spinal TB is an important differential diagnosis, especially in elderly patients or patients coming from countries with a middle-high prevalence of TB.

The Spectrum of Abdominal Tuberculosis in a Developed Country: A Single Institution’s Experience Over 7 Years

SettingPublic hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection.ObjectiveTo determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis.MethodsCross sectional study. All patients ≥18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture.ResultsAmong 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92–0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06–0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45–32.93; p<0.0001).ConclusionsThis study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting.

AimsAbdominal tuberculosis (TB) continues to be a common and challenging abdominal disease in children, with a nonspecific clinical presentation and poor outcomes in delayed diagnosis and complicated cases. We aimed to prospectively evaluate the clinical features and diagnostic workup of children with suspected abdominal TB, with a focus on early initiation of medical and surgical treatment and monitoring of therapeutic outcomes.Materials and methodsA time-bound prospective observational study of all patients ≤ 17 years requiring admission with symptoms suggestive of abdominal TB from February 2020 to May 2023 was conducted. All necessary routine blood tests and imaging were done, and endoscopies and surgeries as needed by the patient were carried out. The data of the patients who were diagnosed as abdominal TB - probable or definitive - were analyzed.ResultsForty-seven patients were recruited with a suspected diagnosis of abdominal TB. Thirty-four patients (24 females and 10 males) were diagnosed as abdominal TB - definite in 18/34 patients (52.94%) and probable in 16/34 patients (47.06%). The mean age was 12.20 ± 3.82 years (4-17 years). Median duration of the symptoms was three months (IQR = 1-5 months). The commonest symptoms were abdominal pain (94.11%), fever (73.52%), and loss of appetite and weight (70.58%). Twelve patients (35.29%) gave a positive history of contact with TB. There were 13/34 (38.23%) patients who had concomitant pulmonary and abdominal TB, and 21/34 (61.76%) patients who had only abdominal TB. Mantoux tuberculin skin test was performed in 20 patients, of which 9/20 (45%) were positive. A Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) was performed in 30/34 patients (88.23%) from fluid or tissue samples, of which 11 patients (35.48%) showed CBNAAT positivity. Fifteen patients (44.11%) underwent surgery, 12 for intestinal perforation and three for intestinal obstruction. Out of the 18 definite cases of abdominal TB, 11/18 (61.111%) were CBNAAT positive, and 10/18 (55.55%) had histopathology suggestive of TB. The 16 probable cases of abdominal TB had a strong history and imaging suggestive of TB abdomen. A total of seven patients who underwent surgery for intestinal perforation expired. One patient developed a relapse, and four patients developed drug-induced liver injury (DILI).ConclusionAbdominal TB remains a common cause of acute abdomen in the pediatric population, often presenting with non-specific features and lacking a definitive diagnostic modality. Early detection through recognition of common clinical features, guided imaging, and timely sampling for confirmation is vital for initiating antitubercular therapy (ATT) and improving outcomes in abdominal TB.

Poor Growth in an 8-year-old Boy from Ethiopia.

This review highlights important contributions published in Respirology and other reputable respiratory journals in 2011 in four principle respiratory medicine areas, namely pulmonary infections, tuberculosis (TB), pleural diseases and chest imaging/interventional pulmonology. The articles have been selected for their insight, reliability and potential impact on clinical practice. From a total of 111 original articles and 40 review papers published in Respirology that year, 34% and 40%, respectively, were devoted to the earlier topics.

Tuberculosis (TB) is an important cause of childhood morbidity and mortality. The burden of childhood disease is not as well documented as that of adult disease, partly because of the difficulty of confirming the diagnosis. In Africa children have been estimated to account for 20-40% of TB case load. Children infected with M. tuberculosis have a high risk of progression to disease, the younger children being at highest risk. Infected children represent a reservoir of future adult disease. The incidence of childhood TB has increased in developing countries. This resurgence is partly attributed to the coexisting burden of human immunodeficiency virus (HIV) disease, which is most pronounced in Sub-Saharan Africa, Nigeria ranking third highest prevalence. The pattern of childhood HIV and TB infection mirror these epidemics in the adult population. The number of children co-infected with HIV and TB is rising, and so is the incidence of congenital and neonatal TB. In addition the emergence of multi-drug resistance TB and extensively drug-resistant TB has occurred within the context of a high prevalence of HIV and TB. The diagnosis of TB has always been difficult in children and is compounded by HIV co-infection. The clinical symptoms in both diseases are similar, and the radiological changes may be non-specific. Treatment of both conditions in children is a challenge due to drug interactions and problems with adherence. There are few stable syrup formulations of antituberculous and antiretroviral drugs in children, and hence division of tablets gives rise to unpredictable dosing and emergence of resistance. To reduce the morbidity and mortality of TB and HIV, existing childhood TB programs must be strengthened, and antiretroviral drug therapy and prevention of mother-to-child transmission programs scaled up. HIV prevalence in the adult population must also be reduced. An increased emphasis on childhood TB, with early diagnosis and treatment, must be a priority.