In the face of a PPD conversion within 2 years, and ruling out current TB disease, INH chemoprophylaxis is indicated, although I thought it was for 6 months and not 9. The rest is not questionable.

In the face of a PPD conversion within 2 years, and ruling out current TB disease, INH chemoprophylaxis is indicated, although I thought it was for 6 months and not 9. The rest is [HIDDEN].

A 32-year-old man, ADVP and recently released from prison, has a protein derivative skin test (PPD) with 10 mm of induration. One year ago, the PPD was negative, he is currently asymptomatic, his HIV serology is negative, and his Chest X-ray is normal. Which of the following approaches do you think is most appropriate?

Do not perform treatment and annual Rx control.

Sputum culture for mycobacteria and treat only if positive.

Treatment with RIF and PRZ for 2 months.

Tuberculosis management

Deviations from the standard regimen There is evidence supporting some deviations from the standard regimen when treating pulmonary TB. Sputum culture-positive patients who are smear-negative at the start of treatment do well with only 4 months of treatment (this has not been validated for HIV-positive patients); sputum culture-negative patients do well on only 3 months of treatment (possibly because some of these patients never had TB at all). It is unwise to treat patients for only three or four months, but all TB physicians will have patients who stop their treatment early (for whatever reason), and it can be reassuring to know that sometimes retreatment is unnecessary. Elderly patients who are already taking a large number of tablets may be offered 9HR, omitting PZA which is the bulkiest part of the regimen.

Isoniazid

Isoniazid has been approved as prophylactic therapy for the following populations: People with HIV infection and a PPD (purified protein derivative) reaction of at least 5 mm induration Contacts of people with tuberculosis and who have a PPD reaction at least 5 mm induration People whose PPD reactions convert from negative to positive in a two-year period – at least 10 mm induration for those up to 35 years of age, and at least 15 mm induration for those at least 35 years old People with pulmonary damage on their chest X-ray that is likely to be due to healed tuberculosis and also have a PPD reaction at least 5 mm induration Injection drug users whose HIV status is negative who have a PPD reaction at least 10 mm induration People with a PPD of greater than or equal to 10 mm induration who are foreign-born from high prevalence geographical regions, low-income populations, and patients residing in long-term facilities

[Consensus document on the diagnosis, treatment and prevention of tuberculosis].

Pulmonary TB should be suspected in patients with respiratory symptoms longer than 2-3 weeks. Immunosuppression may modify clinical and radiological presentation. Chest x-ray shows very suggestive, albeit sometimes atypical, signs of TB. Complex radiological tests (CT scan, MR) are more useful in extrapulmonary TB. At least 3 serial representative samples of the clinical location are used for diagnosis whenever possible. Bacilloscopy and liquid medium cultures are indicated in all cases. Genetic amplification techniques are coadjuvant in moderate or high TB suspicion. Administration of isoniazid, rifampicin, ethambutol and pyrazinamide (HREZ) for 2 months and HR for 4 additional months is recommended in new cases of TB, except in cases of meningitis in which treatment should continue for up to 12 months and up to 9 months in spinal TB with neurological involvement, and in silicosis. Appropriate adjustments with antiretroviral treatment should be made in HIV patients. Combined therapy is recommended to avoid development of resistance. An antibiogram to first line drugs should be performed in all the initial isolations of new patients. Treatment control is one of the most important activities in TB management. The Tuberculin Skin Test (TST) is positive in TB infection when >or=5mm, and Interferon-Gamma Release Assays (IGRA) are recommended in combination with TT. The standard treatment schedule for infection is 6 months with isoniazid. In pulmonary TB, respiratory isolation is applied for 3 weeks or until 3 negative bacilloscopy samples are obtained.

Pulmonary TB should be suspected in patients with respiratory symptoms longer than 2-3 weeks. Immunosuppression may modify clinical and radiological presentation. Chest X-ray shows very suggestive, albeit sometimes atypical, signs of TB. Complex radiological tests (CT scan, MR) are more useful in extrapulmonary TB. At least 3 serial representative samples of the clinical location are used for diagnosis whenever possible. Bacilloscopy and liquid medium cultures are indicated in all cases. Genetic amplification techniques are coadjuvant in moderate or high TB suspicion. Administration of isoniazid, rifampicin, ethambutol and pyrazinamide (HREZ) for 2 months and HR for 4 additional months is recommended in new cases of TB, except in cases of meningitis in which treatment should continue for up to 12 months and up to 9 months in spinal TB with neurological involvement, and in silicosis. Appropriate adjustments with antiretroviral treatment should be made in HIV patients. Combined therapy is recommended to avoid development of resistance. An antibiogram to first line drugs should be performed in all the initial isolations of new patients. Treatment control is one of the most important activities in TB management. The Tuberculin Skin Test (TST) is positive in TB infection when >or=5mm, and Interferon-Gamma Release Assays (IGRA) are recommended in combination with TT. The standard treatment schedule for infection is 6 months with isoniazid. In pulmonary TB, respiratory isolation is applied for 3 weeks or until 3 negative bacilloscopy samples are obtained.

[Chemotherapy of the source and the risk of infection in home contacts].

An attack treatment with 3 drugs during 4-6 months and a consolidation treatment with 2 drugs then INH was applied in 595 cases detected between July 1, 1968 and June 30, 1972, i.e. 264 group A (positive), 200 group B (negative cultures) and 131 group C (pleuretics). The contacts had been in close contact with the source for at least three months before establishing the diagnosis; 549 had been vaccinated at birth with BCG and 209 revaccinated; 413 had undergone chemoprophylaxis with INH.  The control group comprised 1008 subjects, the mean age of the groups being very close; they were followed up for 2 years and 1 month and 2 years and 7 months.  Testing was done every year with 1 u PPD IC 65. The contacts were controlled annually by radiophotography and X-ray and the controls only in case of shifting of the test. Among the contacts there were 44 conversions in the subjects with an initial tuberculin reaction of 0-5 mm and 4 in those with an initial tuberculin reaction of 6-9 mm, representing 15.1% (group A 27.7%, group B 9,8%, group C 10.5%). Three months after the initiation of chemotherapy the proportion of conversions in the three groups (group A 12.3%, group B 5.9%, group C 10.5%) was equal to that of the controls (8.8%). The next year there were 11.2% conversions among the contracts (group A 11.4%, group B 9.6% and C 17.7%) as against 11.9% among the controls. In the first year 8.3% of the contacts contracted tuberculosis (A 15.6%, B 2.4%, C 4.0%) and 0.32% of the controls. The next year 2.8% of the  contacts fell ill (A 4.3%, B 2%, C 0%) and 0.5% of the controls. Among group A contacts aged 0 to 6 years there were 31.7% conversions and 30.7% cases of tuberculosis in the first year, and 7.1% and 1.8% respectively in the following year. Group B and C presented 10.9% conversions and 6% cases of disease in the first year, and no case of tuberculosis in the second year. Chemotherapy reduced conversions and sickness in this group three months after the diagnosis was established.

HIV-1–Associated Opportunistic Infections -- Treatment / Management

Mycobacterium tuberculosis: Drug-susceptible TB infection is treated for 6 months using a combination of isoniazid (INH), pyrazinamide (PZA), rifampin (RIF) or rifabutin, and ethambutol (EMB) for 2 months by directly observed therapy (DOT), followed by INH and RIF for 4 months. In patients with cavitary disease noted on chest X-ray or those with positive cultures, the treatment should be for a total of 9 months with an additional 3 more months of INH and RIF. All patients receiving INH therapy must be prescribed pyridoxine supplements. Extrapulmonary TB except for CNS disease, bone, and joint involvement, should be treated for 6 to 9 months (2 months of INH, PZA, RIF, and EMB, followed by 4 to 7 months of INH and RIF). In patients with CNS, bone, and joint diseases, treatment must be for 9 to 12 months. Intermittent dosing has better medication compliance rates when administered by DOT and achieves higher peak serum concentration. [21]

InternalMed_Harrison

Culture Results Intensive Phase Continuation Phase Extension of Total Treatment Culture positive HRZE for 2 months, daily or intermit-HR for 4 months, daily or 5 d/wk To 9 months, if 2 months of Z is not completed or culture tent (with dose adjustment) or conversion is prolonged and cavitation is evident on plain radiographa HR for 4 months, intermittent (with dose adjustment) Culture negative HRZE for 2 months 2 months To 6 months, if patient is infected with HIV Extrapulmonary HRZE for 2 months HR for 4–7 months, daily or 5 d/wkb To 9–12 months in TB meningitis. Some recommend 9 months for bone/joint TB. Resistant to H QRZEc or, less often, RZES for 6 months … Prolonged culture conversion, cavitation Resistant to R HZEQc (IAd) for 2 months HEQ(S) for 10–16 months Prolonged culture conversion, delayed response

Surgery_Schwartz

when 2 months of treatment has been completed. If cavities were seen on the initial chest radiograph (CXR) or the acid-fast bacillus (AFB) smear results are positive at completion of 2 months of treatment, the continuation phase of treatment should consist of INH and RIF daily or twice daily for 4 months to complete a total of 6 months of treatment. If cavitation was present on the initial CXR and the culture results at the time of completion of 2 months of therapy are positive, the continuation phase should be lengthened to 7 months (total of 9 months of treatment). If the patient has HIV infection and the CD4+ cell count is <100/µL, the continuation phase should consist of daily or three times weekly INH and RIF. In HIV-uninfected patients with no cavitation on CXR and negative results on AFB smears at completion of 2 months of treatment, the continuation phase may consist of either once weekly INH and rifapentine (RPT) or daily or twice weekly INH and RIF to complete a total of 6

Results at 30 months of a randomised trial of two 8-month regimens for the treatment of tuberculosis.

An 8-month isoniazid (INH, H) and ethambutol (EMB, E) based regimen recommended by the World Health Organization (WHO) had never been evaluated in a randomised controlled multicentre trial. To compare, in a non-inferiority study design, two 8-month INH+EMB-based regimens with a standard INH and rifampicin (RMP, R) based regimen. A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly allocated to receive 1) daily EMB, INH, RMP and pyrazinamide (PZA, Z) for 2 months, followed by EMB+INH for 6 months (2EHRZ/6HE); 2) the same drugs in the intensive phase but given three times weekly, followed by the same continuation phase of daily EMB+INH (2(EHRZ)(3)/6HE); or 3) a control regimen with the same intensive phase as in regimen 1, followed by 4 months of daily RMP+INH (2EHRZ/4HR). All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after randomisation. At 30 months, failure/relapse rates were 11.7% of 281 2EHRZ/6HE, 15.3% of 301 2(EHRZ)(3)/6HE and 6.0% of 282 2EHRZ/4HR patients (χ(2), 2 degrees of freedom = 12.8, P = 0.002). These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the standard 6-month regimen. The WHO has withdrawn its recommendation of these regimens.

Heaf test

The reading of the Heaf test was defined by a scale: Negative - No induration, maybe six minute puncture scars Grade 1 - four to six papules (also considered negative) Grade 2 - Confluent papules form indurated ring (positive) Grade 3 - Central filling to form disc (positive) Grade 4 - Disc >10 mm with or without blistering (strongly positive) Grades 1 and 2 could result from previous BCG or avian tuberculosis, rather than human TB infection. Children who were found to have a grade 3 or 4 reaction were referred for X-ray and follow-up. For interpretation of the test, see Tuberculosis diagnosis. Other tests The equivalent Mantoux test positive levels done with 10 TU (0.1 mL 100 TU/mL, 1:1000) are 0–4 mm induration (Heaf 0-1) 5–14 mm induration (Heaf 2) >15 mm induration (Heaf 3-4) The Mantoux test is preferred in the United States for the diagnosis of tuberculosis; multiple puncture tests, such as the Heaf test and Tine test, are not recommended. References

Tuberculosis verrucosa cutis associated with tuberculous lymphadenitis.

A 34-year-old man presented with a large cutaneous lesion on his left thigh that had started as a small papule when he was 13 years of age. The lesion had enlarged slowly over the last 21 years. The patient had received bacillus Calmette-Guérin (BCG) vaccination in childhood. The family history was significant for tuberculosis. Clinical examination revealed a large, purplish-red, indurated plaque measuring 30 x 29 cm on the left thigh, extending to the buttock area. The edges of the lesion had a serpiginous contour with an involuted center (Fig. 1). A left inguinal lymph node was palpated. Chest X-ray and blood cell count were normal. No other focus of disease was identified. Laboratory testing for human immunodeficiency virus (HIV) infection was negative. Purified protein derivative (PPD) intradermal injection disclosed a 19-mm skin induration. Both the cutaneous lesion and the inguinal lymph node were biopsied. Histopathologic sections of the skin fragment showed epidermal hyperkeratosis, neovascular proliferation, and a dense dermal lymphocytic infiltrate. The histopathology of the lymph node demonstrated few granulomas with focal areas of central necrosis. Staining for fungus was negative. Ziehl-Neelsen staining was negative on both the skin and lymph node specimens. Culture for fungus and Leishmania sp. was negative. Tissue culture on Lowenstein-Jensen medium from skin and lymph node was positive for Mycobacterium colonies after 5 and 7 weeks, respectively. Multidrug therapy was instituted with rifampin 600 mg/day, isoniazid 400 mg/day, and pyrazinamide 2 g/day for 2 months, and then rifampin 600 mg/day and isoniazid 400 mg/day alone for the next 4 months. An excellent response was obtained at the end of treatment (Fig. 2).

HIV-infected patients retreated for tuberculosis with intermittent Category II regimen--treatment outcome at 24-month follow-up.

The management of tuberculosis re-treatment in HIV-infected individuals is complex. The clinical and radiological manifestations in this group and response to Category II treatment is not well described. We performed a prospective cohort study of HIV-infected patients retreated for TB due to failure, relapse or default after treatment, at Tuberculosis Research Centre, Chennai, between February 2001 to September 2005. The Category II regimen followed in the TB programme in India (RNTCP) was administered (2 months of Streptomycin (S), Ethambutol (E), INH (H), Rifampicin (R), Pyrazinamide (Z)/1 month of EHRZ/5 months of HRE all given thrice weekly). Antiretroviral treatment was not routinely available at that time. Of the 42 patients enrolled, 35 (83%) were males. The mean age was 33.2 (SD-6.3) years. Cough was the commonest (67%) presenting symptom and opacities were the commonest (48%) radiographic occurrence. 31 patients were culture-positive at baseline, drug susceptibility results showed that 21 (68%) were fully susceptible to all first line drugs, four patients (13%) had MDR TB and four had resistance to INH alone. Among the 31 culture-positive patients, 15 patients (48.4%) completed treatment and were declared cured, of whom two subsequently relapsed. All four MDR patients died. Six patients who received ART, survived. Only 50% of HIV-infected, ART-naive patients who were retreated for tuberculosis using an intermittent Category II regimen had a favourable response to treatment. Early detection of MDRTB and concurrent antiretroviral therapy could contribute to improved outcomes.

Surgery_Schwartz

accuracy. Chest CT scan can delineate the extent of parenchymal disease.Management Medical therapy is the primary treatment of pul-monary tuberculosis and is often initiated before a mycobacte-rial pathogen is definitively identified. Combinations of two or more drugs are routinely used in order to minimize resistance, which inevitably develops with only single-agent therapy. A current treatment algorithm is outlined in Fig. 19-32. Gener-ally, therapy lasts about 26 weeks (2 months intensive therapy followed by 4 months continuation therapy). A 7-month con-tinuation phase should be considered for patients with cavitary pulmonary TB who remain positive on sputum culture after the 2-month intensive therapy, those patients who did not receive pyrazinamide during the intensive phase, HIV-positive patients who did not receive concomitant antiretroviral therapy, and patients treated with INH and rifapentine once weekly (not rec-ommended) who have persistent positive sputum after 2 months of

[Controlled trial of short-term chemotherapy in pulmonary tuberculosis, final study].

178 new cases of tuberculosis of the lungs and pleura have been treated within the period of four years (1985-1988) in military medical institutions of the Y.P.A. The patients were classified by random selection in two therapeutical groups. Two six-month regimens were applied with the same drugs except for the fourth one which was used in the initial period only (EHRZ and SHRZ). Both applied therapeutical combinations were equally successful. All patients achieved negative cultures at least three months after onset of chemotherapy. Relapses occurred in 4 (2.3%) of patients during the period of follow-up for at least 2 and the most 5.5 years after the end of therapy. The toxic effects were tolerable. The drug resistance was found in 25 of 134 (18.6%) patients, the most common to one drug.

Prevalence of latent tuberculosis infection in patients with moderate to severe psoriasis taking biologic therapies in a dermatologic private practice in Miami, Florida.

The reactivation of a latent tuberculosis infection is one of the possible major events that may occur during biologic therapies for inflammatory chronic diseases such as psoriasis. Although its main screening test is regularly used in clinical practice, there are few studies about the prevalence of this silent mycobacterial infection and the rate of positive convertors during treatment. To assess the prevalence of latent tuberculosis infection (LTBI) in patients with moderate to severe psoriasis receiving biologic therapy by using tuberculin skin test as a screening method and to evaluate the rate of conversion of tuberculin skin test (TST) during the treatment with biologics. A total of 445 patients were included in our retrospective study, conducted from January 2006 to September 2012. Tuberculin skin test was performed in all patients prior to treatment and once a year during the follow-up. PPD was considered positive with an induration above 5 mm, following the recommendations of Centers for Disease Control and Prevention/ America Thoracic Society. Data analysis was obtained with SPSS 20.0. The prevalence of LTBI in our population before initiating the treatment was 4.5% by using TST screening method. During the treatment, 10 cases that were initially TST-negative became positive. Only one of the patients developed active tuberculosis infection. The other 9 TST-positive patients were detected during the regular annual screening, and no symptoms or findings on chest x-ray were seen. All the patients were treated with isoniazid (INH) for nine months, and biologic therapy was restarted after one month of treatment with INH without development of overt TB infection in any of them during the follow-up period of the study. The mean time to becoming TST positive from start date was 26.7 months (range from 8 months to 5 years). As the PPD was done annually, it is unknown exactly when the patients became TST positive. Prior to initiating treatment, 20 patients were found to be TST positive. All patients had clear chest x-rays and were treated with nine months of INH prior to initiating biologic therapy at least month later. The use of a screening tool for LTBI is mandatory in patients taking biologic therapies to avoid severe infectious complications. Periodic follow-up is also crucial as positive results may be seen after prolonged use of these agents.

[Efficacy and tolerance of the treatment of tuberculosis in the aged].

We analyzed 55 confirmed cases of tuberculosis in patients over 65, a sample that amounted to 9% of all patients seen in our practice over a period of 5 years. Mean age was 72.4 and the male/female ratio was 4/1. The most frequently associated diseases were tobacco addiction (49%), chronic obstructive pulmonary disease (33%), alcoholism (25%) and prior diagnosis of tuberculosis (20%). Lung involvement was the most common clinical presentation (76%), followed by pleural (9%) and skeletal (7%) involvement. The clinical picture was non specific, with 13% remaining asymptomatic. Cough was the most frequent symptom (45%) and unilateral apical fibrosis with ulceration was the most frequent radiological finding. Pleural discharge and cavitation were demonstrated in 14 and 22%, respectively. Scarring was visible on X-rays in 44%. The tuberculin test was positive in 88% of the cases in which it was performed. Mean delay in diagnosis was 3.4 months; 62% were diagnosed by sputum test, 11% by culture, and 27% histology. In 4% death was directly caused by tuberculosis. Three patients withdrew from treatment, in one case treatment failed, and there was one relapse detected at follow-up. We observed adverse side effects in 33%, and found no statistically significant differences between the 2 therapeutic protocols used (2 months RHS/7 months RH and 2 months RHZS/4 months RH). The incidence of tuberculosis among the elderly is low in our practice and the entity behaves much as it does in the rest of the adult population. Both the efficacy and tolerance of treatment can be considered optimal.

[Two cases of Mycobacterium szulgai pulmonary disease in the elderly].

The rate of pulmonary nontuberculous mycobacteriosis (NTM) in the total pulmonary mycobacteriosis has been continuously increasing. While M. avium complex is the most common cause of NTM, there are a few case reports of pulmonary infection due to M. szulgai. We described two cases of pulmonary NTM caused by M. szulgai. A 75-year-old male was admitted to our hospital because of dyspnea on effort, and productive cough. A chest X-ray showed an infiltrative shadow with cavity in the right upper lobe. A sputum smear for mycobacteria was positive, and a culture grew M. szulgai which was identified by DNA-DNA hybridization. He was treated with isoniazid, rifampicin, and ethambutol. His symptoms and CT and X-ray findings improved, and his sputum smear and culture converted to negative for mycobacteria. Second case was a 73-year-old male who had previously been diagnosed as MAC and pulmonary aspergillosis, and had been treated with antituberculous and antifungal drugs. He was readmitted to our hospital, because of general fatigue and hemoptysis. A chest X-ray revealed a consolidation with bronchiectasis and cavity in the both upper lung fields. A sptum smear for mycobacteria was positive, and a grown culture was identified as M. szulgai. He was treated with rifampicin, ethambutol and kanamycin based on the results of susceptibility testing. After 3 months of this treatment his sputum smear and culture converted to negative for mycobacteria, and his symptoms, and CT and X-ray findings improved.

Evaluation of tuberculosis control by periodic or routine susceptibility testing in previously treated cases.

A national tuberculosis control programme (NTP) disposing of baseline drug resistance rates and using 2EHRZ/6TH in the treatment of new cases. To estimate the extent of drug resistance created by the NTP. Resistance rates in 2EHRZ/6TH failure and relapse cases were compared to baseline, and resistance profiles of repeat isolates were checked. Numbers of observed resistant failures were compared to numbers expected due to pre-existing resistance. Trends of resistance in combined new and previously treated cases were extrapolated. High drug resistance rates were observed. Changes in resistance to streptomycin, the virtual absence of documented acquired resistance and a close match of observed with expected resistant failures all indicated accumulation of primary drug resistance as the main mechanism. Resistance in relapse/failure cases showed a significantly declining trend, and estimated combined drug resistance decreased rapidly. Drug resistance in previously treated cases seems to consist of passed-on primary rather than true acquired resistance. A one-time survey is thus confusing, but continuous routine testing may constitute the best drug resistance monitoring method. Cases previously treated with short-course chemotherapy may show drug resistance much more frequently than generally assumed, and all should receive a re-treatment regimen. The 2EHRZ/6TH regimen proved very safe under field conditions, causing no 'amplification' towards multidrug resistance and almost no acquired isoniazid resistance. Implementation of this regimen, together with a standardised re-treatment regimen, seemed to rapidly reduce isoniazid as well as multidrug resistance levels, despite the fact that directly observed treatment was not strictly applied.

[A case of sarcoidosis with primary acute pulmonary cavitation].

A 23-year-old man was admitted to our hospital on June 24, 1991, because of worsening chest X-ray findings of sarcoidosis. In August 1990, he was referred to our outpatient office, because of BHL and nodular lesions on chest X-ray film performed at his company 4 months earlier. At that time, serum ACE was elevated to 34.0 IU/l, and Ga scintigraphy showed abnormal uptake in bilateral lacrimal and salivary glands, mediastinal and hilar lymph nodes, and in the lung fields. TBLB specimen showed noncaseating epithelioid granuloma with giant cells and negative stains for acid-fast bacilli. Although it was planned to follow this patient without medication, he did not return to our outpatient department. In June 1991, because of worsening of lesions in the lung at annual checkup at his company, he was referred and admitted for steroid therapy. Chest X-ray film on admission showed BHL, multiple nodular lesions in both lung fields, and bullous change in the left upper lobe. Chest CT on admission showed three cavitating lesions within preexisting nodules. PPD skin test was negative, and sputum smears and cultures were repeatedly negative for pyogenic bacteria and acid-fast bacilli. Therapy was initiated with prednisolone 30 mg daily. Four months later, there was marked resolution of BHL and nodular lesions, and the cavitating lesions were no longer visible on chest X-ray film. From the clinical and radiological observations, it is concluded that the cavitating lesions in the present case were primary acute pulmonary cavitation in sarcoidosis, distinct from infection, bullae, or cystic bronchiectasis which are seen in the chronic and fibrotic stages of sarcoidosis.

[Familial tuberculosis: tracing the contacts of an infectious case].

This is a prospective study of 30 cases of smear positive pulmonary tuberculosis, with at least two sputum positive members of the family, seen in the respiratory clinic between January 2003 and June 2004. They constitute the index cases who represent 3.5% of the cases of tuberculosis (n=850) and 2.9% of hospital admissions (n=1034) during the same period. Four patients were HIV positive. In the family circle, all contacts received an intradermal tuberculin test (IDTT) of 10 IU and/or a chest x-ray and/or sputum examination for AFB. Of the 601 contacts 359 (60%) had a positive IDTT with a mean diameter of 13 mm. Active pulmonary tuberculosis was found in 16 contacts giving a prevalence of 2.7% and an incidence of 4.5% (16/359). 67% of the contacts were adults aged 16-87 with a mean age of 35 years. The IDTT was positive with a mean diameter of 12.3 mm. The chest x-ray was abnormal in 40 adults (16.7%) and sputum examination confirmed pulmonary tuberculosis in 14 cases. 33% of the contacts were children (n=119) aged from 3 months to 15 years with the majority (85%) aged under 10. The IDTT was positive with a mean diameter of 12 mm and the chest x-ray was abnormal in 22 cases (18.5%). Two children of 15 years had active tuberculosis. The contacts identified were treated according to the tuberculosis protocol of Senegal (2RHEZ/6EH) with the intensive phase dispensed in hospital. It is of major importance therefore to develop effective strategies of information, education, diagnosis and management for cases of infectious pulmonary tuberculosis.

Primary Cutaneous Coccidioidomycosis Presenting as a Recurrent Preauricular Cyst.

A 31-year-old Filipino active duty marine presented with a 2-year history of a waxing and waning nodule on his left cheek that had been incised and drained on multiple occasions. The patient had no significant medical history other than a positive purified protein derivative test with negative chest x-ray finding treated with a 9-month course of isoniazid in 2010. He denied cough, fever, chills, night sweats, weight loss, joint/bone pain, or prior trauma to the area. On initial examination, there was a 1×1-cm erythematous indurated nodule associated with an overlying violaceous scar on his left preauricular cheek. Since the lesion was presumed to be an inflamed epidermal cyst, it was initially treated with 0.1 cc of interlesional triamcinolone acetonide (10 mg/cc). At 1-month follow-up, the lesion was slightly less indurated, but an excisional biopsy was performed to remove the residual nodule. The biopsy showed an essentially normal epidermis with focal dermal fibrosis below which were multiple collections of histiocytes and multinucleated giant cells surrounded by a dense lymphoplasmacytic infiltrate with numerous eosinophils (Figure 1). A few multinucleated giant cells contained large thick-walled spherules, some with endospores, consistent with Coccidioides immitis (Figure 2). Serological tests showed positive serum for C immitis IgG antibodies with low levels of complement-fixing antibodies (1:2). IgM antibodies were negative. Findings from chest x-ray and bone scan failed to reveal evidence of systemic disease. Although the infectious disease physician felt that the patient most likely had primary cutaneous coccidioidomycosis (PCC), since the duration of the infection was unknown and the patient was Filipino, thereby increasing his risk of dissemination, he was placed on a daily regimen of 400 mg of oral fluconazole until his complement fixation titers became undetectable.

[The efficacy of ethambutol compared to streptomycin in the initial quadruple phase of short-term regimens].

In order to test comparatively SM and EMB efficacies within quadruple regimens of short-term chemotherapy, two groups of patients with pulmonary tuberculosis at first treatment, sputum positive under microscopic examination, were constituted through randomization. One group (59 cases) was submitted to the standard regimen RHSZ 2/7, and the other (61 cases) to RHZE 2/7. Group structure was homogeneous from the standpoint of case repartition, according to the anatomo-radiological form, therapeutical regimen, and sensitivity to Tb drugs. Both bacteriological and radiological clinical evolutions show, even in the conditions of a short-time interval (2 months), a similar efficacy of SM and EMB within the quadruple regimens in the initially intensive phase of anti-Tb treatment. It is possible that the results may be dependent upon the concomitantly bactericidal action of: rifampicin, hydrazide and pyrazinamide. Therefore, a further testing of the comparative efficacy of the triple regimen RHZ 2/7 with the quadruple RHSZ 2/7 and RHZE 2/7 during a longer follow-up is required.

Tuberculosis management

There are several treatment regimens available: 9H—Isoniazid for 9 months is the gold standard and is 93% effective. 6H—Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The US guidance exclude this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions). (69% effective) 6 to 9H2—A twice-weekly regimen for the above two treatment regimens is an alternative if administered under Directly observed therapy (DOT). 4R—Rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB. 3HR—Isoniazid and rifampicin may be given for 3 months. 2RZ—The 2-month regimen of rifampicin and pyrazinamide is no longer recommended for treatment of LTBI because of the greatly increased risk of drug-induced hepatitis and death.

[Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature].

We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC 1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days. The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption. After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all drugs were withdrawn again. The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately. He was thereafter treated with INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002. Late in September, she complained of appetite loss. The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis. On admission examination of blood count and blood chemistry were normal. Treatment with RFP, INH and SM was started on March 11. He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding. Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26. Autopsy showed generalized aspergillosis. It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia. We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature.

Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis?

Pinetown, South Africa (1975-1983). To determine the value of previous treatment history and sputum smear examination at 2-3 months in predicting treatment failure and relapse in tuberculosis patients treated with four drugs given twice weekly for six months under direct observation. Four cohort studies among 562 ambulant adults with culture positive pulmonary tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg, rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice weekly. The same drug regimen was given to all patients irrespective of previous treatment history. Therapy was not changed if smears remained positive at 2-3 months. Positive predictive values of a history of previous treatment for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse (9.4%) were poor. Although patients with positive smears at 2-3 months were more likely to fail therapy than patients with negative smears (relative risk=4.5, 95% Confidence Interval [CI]: 1.6-12.8), positive predictive value for treatment failure was only 12.5%. Although relapse was more frequent in patients with positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most patients who relapsed had been smear negative at 2-3 months (18/21). A four-drug rifampicin-containing regimen can safely be given twice weekly under direct observation to both new and retreatment cases, and the 2-3 month smear examination can safely be omitted.

Latent tuberculosis

There are several treatment regimens currently in use: 9H — isoniazid for 9 months is the gold standard (93% effective, in patients with positive test results and fibrotic pulmonary lesions compatible with tuberculosis). 6H — Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The U.S. guidance excludes this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions) (69% effective). 6 to 9H2 — An intermittent twice-weekly regimen for the above 2 treatment regimens is an alternative if administered under Directly observed therapy (DOT). 4R — rifampicin for 4-months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB. 3HR — Isoniazid and rifampin may be given daily for three months.

Surgery_Schwartz

on AFB smears at completion of 2 months of treatment, the continuation phase may consist of either once weekly INH and rifapentine (RPT) or daily or twice weekly INH and RIF to complete a total of 6 months of treatment (bottom). For patients receiving INH and RPT whose 2-month culture results are positive, treatment should be extended by an additional 3 months (total of 9 months). *EMB may be discontinued when results of drug susceptibility testing indicate no drug resistance. †PZA may be discontinued after it has been taken for 2 months (56 doses). ‡RPT should not be used in HIV-infected patients with tuberculosis or in patients with extrapulmonary tuberculosis. §Therapy should be extended to 9 months if results of 2-month culture are positive. (Reproduced with permission from Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis, Am J Respir Crit Care Med.

Cutaneous manifestations of Strongyloides stercoralis hyperinfection in an HIV-seropositive patient.

A 41-year-old human immunodeficiency virus (HIV)-positive man was hospitalized with complaints of a 4-week history of nausea and vomiting, associated with decreased oral intake, and a 4-day history of frontal headache and fever. His medical history was significant for a gunshot wound to the head 3 years prior, with a residual seizure disorder. He also had two previous hospitalizations, both for culture-negative bacterial meningitis; the first episode occurred 12 months before admission and the second episode occurred 5 months later. At that time, he was found to be positive for serum antibodies against HIV and a CD4+ T-lymphocyte count of 126/mm3. He had no known drug allergies and was not receiving any medication. On admission, the patient was febrile (104.0 degrees F) and hypotensive (blood pressure, 92/40 mm Hg). Pertinent physical examination findings included cachexia with bitemporal wasting, dry mucus membranes, adherent white patches on the oral mucosa, and negative Kernig's and Brudzinski's signs. His laboratory results revealed macrocytic anemia, a decreased serum sodium of 125 mEq/L, and a normal total leukocyte count with a CD4+ T-lymphocyte count < 50/mm3. Lumbar puncture opening pressure was elevated at 160 mm Hg, and cerebrospinal fluid analysis showed an increased white cell count of 97/microL (84% lymphocytes), a decreased glucose level of 26 mg/dL, and a decreased protein level of 42 mg/dL. The patient was started on empiric therapy that included intravenous ampicillin and cefotaxime, oral Bactrim, and clotrimazole lozenges for thrush. Cerebrospinal fluid culture was positive for Escherichia coli, sensitive to cefotaxime. Two days later, the patient developed fine, erythematous, nonblanchable macules primarily on his abdomen, with minimal involvement of his thorax and back. His skin lesions remained unchanged for the next 2 weeks. Repeat lumbar puncture was performed after 14 days of cefotaxime. The cerebrospinal fluid analysis showed an elevated white cell count of 7/microL (100% lymphocytes), a decreased glucose level of 53 mg/dL, and a decreased protein level of 33 mg/dL. The cerebrospinal fluid culture was now positive for Pseudomonas aeruginosa resistant to cefotaxime. The patient was started on imipenem. On day 34 of his admission, the patient became tachypneic with complaints of dyspnea. A chest roentgenogram revealed bilateral patchy infiltrates. He was transferred to the intensive care unit and intubated for hypoxemic respiratory failure (arterial blood gas values on 6 L of oxygen: pH, 7.46; bicarbonate, 23; and oxygen saturation, 37). That evening, the patient was also noted to have diffuse petechiae and purpura in a reticulated pattern over his abdomen (Figure 1A and 1B), most heavily concentrated in the periumbilical region, extending to the axillae and upper thighs. A 3x3-mm punch biopsy from abdominal skin demonstrated Strongyloides stercoralis larvae in the dermis (Figure 2A and 2B). His sputum specimen was teeming with adult S stercoralis worms (Figure 3) and, subsequently, numerous S stercoralis larvae were observed not only from the bronchoalveolar lavage but also from the nasogastric fluid specimen. These findings confirmed the diagnosis of disseminated strongyloidiasis. On hospital day 35, the patient was doing poorly and was started on thiabendazole (1250 mg twice daily for 28 days). Nine days later, ivermectin (4.5 mg once daily for 3 days for 2 courses) was also added. He continued to clinically deteriorate. The patient died 31 days after systemic antihelminthic treatment was initiated.

[Efficacy of regimens containing INH, RFP with varied chemotherapy courses on retreated culture positive pneumoconio-tuberculosis].

To evaluate the short and long-term effects of regimens containing INH, RFP with varied chemotherapy courses on culture-positive pneumoconio-tuberculosis. 79 patients with culture-positive pneumoconio-tuberculosis were divided into three groups according to chemotherapy duration: 9-months group (M9: 2SHRZ/7HRE) 28 cases, 12-month group (2SHRZ/10HRE) 25 cases, 18-month group (M18: 2SHRZ/10HRE/6HR) 26 cases. Evaluating the efficacy of regimens depended predominantly on sputum bacteriological conversion, and the patients who completed the regimens were followed up for 5-8 years. Sputum negative conversion rates of three groups at the end of chemotherapy were 83%, 96%, 95%, and their recurrent rates in follow-up period 41%, 4% and 5% respectively. Of all patients who completed the regimens bacteriological relapse rates from the first to fourth year are 6%, 8%, 2%, 2% in the follow-up period. There was no bacteriological relapse from fifth to eighth year. It is effective for SHRZ/HRE combination with 12-months course to retreated tubercle bacillus positive pneumoconio-tuberculosis, and it is appropriate for such patients to be followed up for 4-5 years.

Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases.

New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 x 105 cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted.

[The therapeutic effect of regimens containing isoniazid and rifampicin for pulmonary tuberculosis with single isoniazid or rifampicin resistance].

To study regimens containing isoniazid and rifampicin for the treatment of pulmonary tuberculosis with isoniazid or rifampicin resistance. Eighty patients with isoniazid or rifampicin resistance, and whose sputum were still positive at the end of 2-month therapy with isoniazid (H), rifampicin (R), pyrazineamide (Z) and ethambutol (E), were retrospectively analyzed from Jan.2009 to Dec.2012 in Guangzhou Chest Hospital. According to the Mycobacterium drug sensitive test (DST) before the treatment with isoniazid and rifampicin, the patients were divided into the sensitive group (either H or R sensitive), the multidrug-resistance group (both H and R resistance) and the single-resistance group (H or R resistance). There were 80 patients (57 females, 23 males) whose sputum was still positive at the end of 2 month treatment. Their ages ranged from 16-80 (average 45) years. Among them, 29 received the first-treatment, while 51 received retreatment. There were 37 cases in the sensitive group, with 18 first-treatment patients and 19 retreatment patients. There were 15 cases in the single-resistance group, with 3 first-treatment patients and 12 retreatment patients. There were 28 cases in the multidrug-resistance group, with 8 first-treatment patients and 20 retreatment patients. After treatment, mycobacterial conversion to MDR-TB occurred in 2 patients in the sensitive group, and in 6 patients in the single-resistance group. The rate of conversion to MDR-TB was higher in the single-resistance group than that in the sensitive group (χ² = 12.849, P = 0.000).Six patients with single H resistance converted to MDR-TB and 2 patients with single R resistance converted to MDR-TB (P < 0.05, RR = 18.0). Single H or R drug-resistance was more common in retreated patients with pulmonary tuberculosis.If regimens containing isoniazid and rifampicin was used to treat patients with single H or R drug-resistance, resistant enlarging effect may appear and lead to MDR-TB. The retreated patients should be monitored as soon as possible for detection of Mycobacterium resistance to H and R, and regimens for H or R-resistance should be used to prevent resistant enlarging effect.

Pearls and oy-sters: tuberculous meningitis: not a diagnosis of exclusion.

A 21-year-old man presented to his local emergency department with 5 days of headache, which was dull, occipital, bilateral, nonthrobbing, and progressively worsening. It was associated with mild fever, photophobia, and neck pain and stiffness. He had no history of headache, chronic illness, recent vaccinations, cutaneous rash, cough, diarrhea, arthralgia, or myalgia. He was from Ecuador and had been living in the United States for less than 1 year. He had been incarcerated while in Ecuador. Sublingual temperature on admission was 102.6°F. Other vital signs were within normal limits. On physical examination, he appeared thin but not cachectic. He had meningismus and photophobia, but no papilledema and his mental status was alert and attentive. There were no focal neurologic deficits. CSF contained red blood cells: 24 × 10(3)/μL; white blood cells: 85/μL (lymphocytic predominant); protein: 128 mg/dL; and glucose: 48 mg/dL (CSF/serum glucose ratio = 0.53). CSF Gram stain and cultures, PPD test, and blood and urine cultures were all negative. CT scan of the head on day of admission was entirely normal. MRI without gadolinium contrast showed a single punctate T2 hyperintensity in the left frontal periventricular white matter. Chest radiograph was clear. He received empiric vancomycin, ceftriaxone, and acyclovir. Corticosteroids were not given. The patient did not improve with antibiotics and continued to be intermittently febrile. On day 5, he became abruptly more somnolent, then comatose, opening eyes only to pain, his pupils were 5 mm and reactive, he had intact brainstem reflexes, withdrawing both arms and legs. Emergent head CT showed development of hydrocephalus and a ventriculoperitoneal shunt was emergently placed. The neurologic examination did not improve after shunt placement, and repeat head CT showed increased hydrocephalus with bilateral cerebral infarcts. On day 11, he was transferred to Columbia University Medical Center for intensive care. He was febrile and comatose. He did not open his eyes to pain, pupils were 7 mm minimally reactive, brainstem reflexes were intact, and he exhibited extensor posturing to pain. Mannitol was given, corticosteroid therapy was started, and an extraventricular drain was placed. The next day, his right pupil was 8 mm and nonreactive. MRI showed diffuse contrast enhancement of the arachnoid, extensive infarction of basal ganglia, midbrain, and pons, and small ring-enhancing lesions in the cerebellum (figure 1, A-D). Repeat lumbar puncture showed red blood cells: 550 × 10(3)/μL; white blood cells: 250/μL (14% neutrophils, 80% lymphocytes, 6% monocytes); protein: 65 mg/dL; and glucose: <10 mg/dL (CSF/serum glucose ratio = 0.08). CSF testing for Cryptococcus and toxoplasmosis was negative. CSF acid fast bacilli (AFB) smear was negative ×2, and CSF nucleic acid amplification test was also negative for tuberculosis. Serum HIV test was negative. Not until 14 days after initial presentation and 3 days after transfer to the intensive care unit was antituberculosis therapy finally started, because the pattern of infarcts on the MRI suggested basilar meningitis and he had not improved on broad-spectrum antibiotics. That same day, the first sputum AFB smear was positive, as were all succeeding daily sputum AFB smears. Tuberculosis nucleic acid amplification was positive from the sputum, but persistently negative from the CSF. Daily portable chest radiographs had been normal (read as likely atelectasis), but chest CT showed dense consolidations in the left lung and diffuse micronodular opacities throughout both lungs. Two days later, only 21 days after the onset of his headache, the patient died of cardiopulmonary arrest secondary to transtentorial cerebral herniation. Thirteen days later, the CSF culture became positive for Mycobacterium tuberculosis sensitive to streptomycin, isoniazid, ethambutol, rifampin, and pyrazinamide.