Low risk of relapse and deformity among leprosy patients who completed multi-drug therapy regimen from 2005 to 2010: A cohort study from four districts in South India.

INTRODUCTION: Relapse of leprosy among patients released from treatment (RFT) is an indicator of the success of anti-leprosy treatment. Due to inadequate follow-up, relapse in leprosy patients after RFT is not systematically documented in India. Relapsed leprosy patients pose a risk in the transmission of leprosy bacilli. We determined the incidence of relapse and deformity among the patients RFT from the leprosy control programme in four districts in South India. METHODS: We conducted two follow-up surveys in 2012 and 2014 among the leprosy patients RFT between 2005 and 2010. We assessed them for any symptoms or signs of relapse, persistence and deformity. We collected slit skin samples (SSS) for smear examination. We calculated overall incidence of relapse and deformity per 1000 person-years (PY) with 95% confidence intervals (CI) and cumulative risk of relapse. RESULTS: Overall, we identified 69 relapse events, 58 and 11, during the first and second follow-up surveys, respectively. The incidence of relapse was 5.42 per 1000 PY, which declined over the years after RFT. The cumulative risk of relapse was 2.24%. The rate of deformity among the relapsed patients was 30.9%. The overall incidence of deformity was 1.65 per 1000 person years. The duration of M. leprae detection in smears ranged between 2.38 and 7.67 years. CONCLUSIONS: Low relapse and deformity rates in leprosy RFT patients are indicative of treatment effectiveness. However, a higher proportion of detection of deformity among relapsed cases is a cause for concern. Periodic follow-up of RFT patients for up to 3 years to detect relapses early and ensure appropriate treatment will minimize the development of deformity among relapsed patients.

Cytological diagnosis in a clinically unsuspected case of disseminated BCGosis: A case report.

Bacille Calmette-Guerin (BCG) vaccine is administered worldwide to neonates and considered safe. Serious complications like disseminated BCGosis are extremely rare occurrences (<1 per million vaccinations). A 6 months male was brought to paediatric outpatient department with fever and swelling over the dorsum of the left hand for 5 days. On examination, he was febrile and had hepatosplenomegaly. X-ray of the hand showed lytic lesions in the first and second metacarpals. Provisional clinical diagnosis included Langerhans cell histiocytosis, congenital syphilis, and haematological malignancy. Fine Needle Aspiration Cytology (FNAC) was done from the swelling and showed diffuse sheets of histiocytes with both intracellular and extracellular rod-shaped unstained structures along with inflammatory cells. These ghost images stained positive with ZN stain. A cytological diagnosis of atypical mycobacteria vs leprosy was made. Child was revisited and found to have an active BCG scar. Further investigations showed low serum IgM and positive AFB culture. These bacilli were confirmed by GenoType MTBDR plus test as Mycobacterium bovis. Despite Antitubercular therapy, the patient succumbed to death. This case highlights the variable clinical presentation of BCGosis. Its occurrence may unmask any underlying immunodeficiency. If unfamiliar with the above cytological features and in absence of routinely performed special stains, the cytopathologist may miss these notorious organisms and treat such cases like suppurative lesions. To conclude, an early and definitive diagnosis of BCGosis can be established on FNAC which would ensure timely management and better outcome in this highly lethal entity.

Acute scrotum: Hansen's disease versus filariasis.

Hansen's disease is caused by Mycobacterium leprae. The disease is known to involve the visceral organs including the testis apart from the skin and nerves in the lepromatous pole of leprosy due to widespread hematogenous dissemination of lepra bacilli. Furthermore, there can be testicular pain during the type 2 reaction in Hansen's disease. Filariasis is a disease caused by the parasitic nematode, Wuchereria bancrofti. This infection most commonly results in lymphedema and secondary vaginal hydrocele with an associated epididymo-orchitis. Acute epididymo-orchitis is either seen in the acute phase or as a part of secondary bacterial infections. The particular interest of this paper is to report the case of Hansen's disease who presented with testicular pain and posed a diagnostic dilemma when his pain did not respond to the standard mode of treatment and an alternate rare diagnosis was sought. This case report also emphasizes the need of reconsideration of diagnosis when the patient is not responding to standard therapy.

A Breast Lump in an Elderly Lady - Carcinoma or else ?.

Breast tuberculosis (TB) is rare form of extra-pulmonary TB. It is most commonly seen in women of reproductive age group, especially in young, multiparous women who are breast feeding. In geriatric women, breast TB in some cases simulates with breast carcinoma due to common signs which include hard breast lump with nodular surface, ulceration, fixity to skin, discharging sinus, retraction of nipple, axillary lymphadenopathy etc. Hence, it is very difficult to differentiate breast TB from breast cancer, especially in elderly women on clinical ground only, and therefore, histopathological diagnosis is mandatory. Fine needle aspiration cytology is frequently inconclusive due to very small amount of tissue material, and open biopsy or lumpectomy followed by histopathological examination is necessary to confirm the diagnosis of breast TB. Six-month course of anti-tuberculous therapy - ATT (rifampicin, isoniazid, pyrazinamide and ethambutol) is adequate for complete resolution. Here, we report a case of breast TB in an elderly women presenting with left sided breast lump with ulceration of overlying skin and ipsilateral axillary lymphadenopathy. This case of tuberculous mastitis was suspected to be carcinoma due to presence of hard, tender, breast lump with irregular margin, nodular surface, ulceration, purulent discharge and ipsilateral axillary lymphadenopathy in absence of any constitutional symptoms of TB, and heterogenous, hypoechoic mass on USG, which was confirmed by histopathological examination of resected breast lump and responded fully to ATT.

A case of lepromatous leprosy with co-existing tuberculosis verrucosa cutis (TVC).

The association of leprosy and cutaneous tuberculosis has been reported rarely. Though cross-immunity may exist between these two mycobacterial infections, tuberculosis can occur throughout the spectrum of leprosy. We report a case of lepromatous leprosy with Type II reaction, with tuberculosis verrucosa cutis (TVC). The patient presented with multiple skin-coloured tender nodules of variable size, involving the upper and lower extremities, nodular enlargement of both ear lobes, erythematous plaques on the face and icthyotic patches over both lower legs and feet, for 6 months. There was also a slow-growing asymptomatic warty plaque over the right lateral malleolus, present for 1 year. Slit skin smear examination from ear lobes, forehead and nodules, and histopathology of the warty lesion, respectively confirmed the diagnoses of leprosy and tuberculosis.

Compounds for use in the treatment of mycobacterial infections: a patent evaluation (WO2014049107A1).

Tuberculosis is one of the main causes of mortality with 1.5 million deaths a year worldwide. The growing emergence of multi- and extremely resistant strains highlights the urgent need of novel antibiotic strategies. Ethionamide, interfering with the mycobacterial membrane biosynthesis, is used in second-line treatment. This molecule is a prodrug, which requires activation by EthA. The patent described in this evaluation (WO2014049107A1) claimed a new family of molecules and their use as antibiotic treatment against mycobacteria such as Mycobacterium tuberculosis, M. leprae and atypical mycobacteria, either as a single active agent or in combination with antibiotics activable by EthA pathway.

Validation of indirect tuberculosis treatment adherence measures in a resource-constrained setting.

SETTING: Arusha, Mwanza, Mufindi and Kilosa in Tanzania. OBJECTIVE: To assess the test characteristics of three indirect adherence measures against a gold standard of direct measurements of drug intake for use in a resource-constrained setting. METHODS: We assessed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and the diagnostic odds ratio (dORs) of three indirect adherence measurement tools against direct measurement in urine using the IsoScreen assay. RESULTS: The single adherence question of missed doses in the last 2 days had the highest dOR (40.3) compared to the Morisky medication adherence scale (MMAS, 2.5) and pill counts (3.4). The sensitivities of these measures were respectively 97.9%, 92% and 89.6%. Specificity ranged from 46.4% (adherence question) to 17.9% (MMAS). The PPVs of adherence question, pill counts and MMAS were respectively 97.6%, 96.5% and 94.2%, while the NPVs ranged from 50% (adherence question) to 3.1% (MMAS). CONCLUSION: Among several instruments for indirect adherence measure in the routine setting of the Tanzanian National Tuberculosis and Leprosy Programme, a single adherence question was found to have the best discriminatory power. However, the single adherence question might not adequately identify patients who are non-adherent. Confirmatory studies are needed, especially in settings with low adherence rates.

Oral drug provocation test to generate a list of safe drugs: experience with 100 patients.

BACKGROUND: Following a drug eruption, patients and their doctors need to know which drugs can be safely administered for subsequent illnesses. Currently available laboratory tests are unable to answer this question in a clinically meaningful manner. AIMS: To describe our use of oral provocation tests to provide a list of safe drugs to patients. METHODS: We studied the records of 100 patients who underwent oral provocation testing in our department between 2003 and 2009. All patients were admitted to hospital and drugs were administered under supervision, one drug per day. A dermatologist evaluated all symptoms and signs that developed following drug intake. RESULTS: Sixty nine women and 31 men underwent provocation testing. There were 96 reactions in 61 patients, of which 44 reactions in 34 patients were judged to be true reactions. All reactions could be controlled, with treatment or spontaneously. A list of safe drugs was provided to the patient along with written instructions to avoid any drug(s) that had produced a reaction. CONCLUSIONS: Oral provocation tests are safe and effective in providing patients with a list of drugs they can take safely. These tests should preferably be undertaken after admitting the patient to hospital.

Assessment of knowledge and practice of private practitioners regarding tuberculosis control in Ethiopia.

INTRODUCTION: Ethiopia has a growing private health sector. In recent years, the directly observed treatment short course (DOTS) strategy was initiated in selected private health facilities in the country. The objective of the present study was to assess knowledge and practice of private practitioners in tuberculosis (TB) control in Amhara Region, Ethiopia. METHODOLOGY: An institution-based cross-sectional study was conducted among 112 private practitioners selected from all private health facilities in the region. The study was conducted between May and August 2008 and data was collected using a semi-structured questionnaire. Group differences were analyzed using the chi-square test. RESULTS: Fifty-nine (52.7%) of the private practitioners suspected TB in patients with three weeks' duration of cough. Only 37 (33.0%) of the private practitioners were able to precisely list the correct treatment regimens for all categories as recommended in the National Tuberculosis and Leprosy Control Program guidelines. The correct frequency of TB treatment monitoring was provided by 44 (50%) of the respondents. Overall 44 (39.3%) of the private practitioners did not have satisfactory knowledge about the directly observed treatment short course (DOTS) strategy. Those who attended DOTS training during the two years prior to the survey were more likely to have satisfactory knowledge compared to those who did not receive training (OR 4.45, 95% CI: 1.33, 14.87, p < 0.02). CONCLUSION: A significant proportion of private practitioners did not have satisfactory knowledge and practice about DOTS. The provision of regular DOTS refresher courses improves TB management for patients in the region.

Treatment delay among tuberculosis patients in Tanzania: data from the FIDELIS initiative.

BACKGROUND: Several FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP) during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on treatment delay and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB) patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis. METHODS: Treatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study. RESULTS: We included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays. CONCLUSION: In this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had a 25% longer median delay.

Quality of tuberculosis care in six health facilities of Afar Region, Ethiopia.

BACKGROUND: Quality tuberculosis care plays an important role in the status of tuberculosis (TB) control, treatment completion and adherence. Nonetheless, very little is known about the quality of TB care in public health facilities in Ethiopia. In this study we assessed the quality of TB care delivery in Afar Region of Ethiopia. METHODS: A descriptive cross sectional health institution based survey with both semi-structured and structured questionnaires was employed. A mix of complementary techniques was administered Data were collected between 5th February and 10th March 2007 from six health institutions. Records were reviewed for 270 patients, exit interviews were made for 209 patients, six providers were interviewed & 49 patients were observed Data was collected by trained nurses and analyzed using SPSS 11.0 statistical software. RESULTS: The study had showed that delivery of materials, drugs and supplies for tuberculosis control activities were fairly good. Staffing qualities were poor and patterns of supervision were weak. A relatively higher proportion of patients were dissatisfied with the appropriateness and adequacy of working hours (63.6%) and waiting time (70.3%). Statistically significant correlation was observed between process quality and output quality (clients' satisfaction) parameters (p < 0.001). CONCLUSION: Continues quality improvement mechanisms to improve the different aspects of the programme and adherence to the National Tuberculosis and Leprosy Control Program guideline could be important interventions to enhance the quality of care delivery. An expanded community-based study to better guide quality DOTS program in pastoralist communities is crucial.

The diarylquinoline R207910 is bactericidal against Mycobacterium leprae in mice at low dose and administered intermittently.

The diarylquinoline R207910 is profoundly bactericidal in a murine model of tuberculosis. Previously, R207910 was also found to be bactericidal for Mycobacterium leprae-infected mice during lag phase. Herein we evaluate the bactericidal efficacy of R207910 (1 to 120 mg/kg of body weight) when administered five times weekly, once weekly, and once monthly during logarithmic multiplication of M. leprae organisms. All treatments were found to be bactericidal, suggesting that both low and intermittent dosing with R207910 holds promise for leprosy patients.

What is the appropriate duration of a therapeutic trial in cutaneous tuberculosis? Further observations.

BACKGROUND: Laboratory tests for the diagnosis of cutaneous tuberculosis lack adequate sensitivity and specificity and a trial of therapy is often used as a diagnostic test in difficult cases. However, the duration for which the trial should be undertaken is not clearly defined. Our previous study indicated that one month of therapy was adequate to detect a clinical response to treatment. However, about half the patients first reported after one month of treatment, some much later. METHOD: We therefore analysed the treatment records of 107 patients who received four-drug, short course, antitubercular therapy for a diagnosis of cutaneous tuberculosis in our hospital and who were asked to return for follow-up at biweekly intervals in the first month of treatment. RESULT: Twenty-one patients did not return for any follow-up visit, nine patients did not respond to treatment and treatment was stopped in one patient. Of the remaining 76 patients, 72 patients were recorded to have distinct clinical improvement within five weeks of starting treatment while only four patients showed improvement after 60-123 (8-17 weeks) days of therapy. CONCLUSION: These findings indicate that five weeks appears to be an adequate duration of a therapeutic trial in patients suspected to have cutaneous tuberculosis, with the exception of tuberculids and patients showing minimal clinical activity before treatment. Patients who have not responded by this time are unlikely to do so with further treatment and should have their diagnosis reviewed.

Renal hypersensitivity vasculitis associated with dapsone.

We describe clinical and pathological features of kidney and skin involvement in a patient with hypersensitivity vasculitis associated with dapsone. Although visceral damage occurs rarely, similar skin and kidney histopathologic and immunohistochemical findings indicate that this organ is a target for type IV cell-mediated dapsone reaction. To our knowledge, this is the first reported case of renal hypersensitivity vasculitis associated with dapsone.

Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.

BACKGROUND: Clofazimine is potentially useful for the treatment of disease due to multidrug resistant Mycobacterium tuberculosis, as well as leprosy and certain chronic skin diseases. Its pharmacokinetics have been incompletely characterized. This study was conducted to explore issues relating to bioavailability in the presence of food, orange juice, and antacid. METHODS: A 5 drug regimen consisting of clofazimine, cycloserine, ethionamide, para-aminosalicyclic acid, and pyridoxime was administered to healthy subjects four times using a four period cross-over design with two weeks washout between treatments. Subjects also received orange juice, a high fat meal, aluminum/magnesium antacid, or only water in random order with the drug regimen. The pharmacokinetics of clofazimine were assessed using individual- and population-based methods and relative bioavailability compared to fasting administration was determined. RESULTS: Clofazimine exhibited a sometimes prolonged and variable lag-time and considerable variability in plasma concentrations. From the population analysis (one-compartment model), the mean oral clearance was 76.7 l/h (CV=74.2%) and mean apparent volume of distribution was 1470 l (CV=36.3%). The first-order absorption rate constant ranged from 0.716 to 1.33 h(-1) (pooled CV=61.7%). Residual (proportional) error was 49.1%. Estimates of bioavailability compared to fasting administration were 145% (90% CI, 107-183%) for administration with high fat food, 82.0% (63.2-101%) for administration with orange juice, and 78.5% (55.1-102%) for administration with antacid. CONCLUSION: Administration of clofazimine with a high fat meal provides the greatest bioavailability, however, bioavailability is associated with high inter- and intra-subject variability. Both orange juice and aluminum-magnesium antacid produced a reduction in mean bioavailability of clofazimine.

Anti-tuberculosis treatment in private pharmacies, Kathmandu Valley, Nepal.

SETTING: Urban municipality of 150000 citizens in Kathmandu Valley, Nepal. OBJECTIVE: To determine 1) the perceptions among private pharmacists of characteristics of tuberculosis (TB) patients visiting private pharmacies in the area, 2) the sales of different anti-tuberculosis drugs, and 3) the interaction between private health providers and pharmacists. DESIGN: Between January and April 1998, semi-structured interviews were conducted with 98% (49/50) of the private drug-retailers in the area. RESULTS: Thirty-two (65%) pharmacies had sold anti-TB drugs during the last month. Forty-three (88%) said that most TB patients were of low socio-economic status and rarely bought drugs for more than a week at a time. Only eight (16%) reported that TB patients usually returned to buy the full course of drugs. Seventy-two per cent of total spending on anti-tuberculosis drugs was for different kinds of combinations of drugs. Nine per cent was spent on plain rifampicin, believed to be sold only to tuberculosis/leprosy patients. During the previous month, 5/13 (38%) of pharmacies with no doctors attached had sold anti-tuberculosis drugs compared with 27/38 (71%) of pharmacies with doctors attached to them (P < 0.05). CONCLUSION: The private sector offers an available and acceptable but non-affordable service for many TB patients. A substantial amount of anti-TB drugs are being sold in the private pharmacies. There is therefore a potential role for pharmacists to play in collaborative efforts between the private and public sector in TB control activities.

Tuberculosis control in resource-poor countries: alternative approaches in the era of HIV.

PIP: WHO projections suggest that the annual number of tuberculosis (TB) cases worldwide will reach 10.2 million by the year 2000. HIV plays a dominant role in this increase in many resource-poor countries. The internationally recommended treatment regimens for TB combine some of the six major antituberculosis drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, and thiacetazone. WHO treatment guidelines give priority to patients according to the nature of their disease and recommend two regimens of 6-8 months duration, the longer regimen incorporating thiacetazone. Recently, WHO has favored a 6-month treatment regimen given as directly observed therapy (DOT). The disadvantages of the standard approach are the heavy workload of smear examinations, the complexity of some drug regimens, and the low rates of therapy completion. With the increasing TB case load in areas of high HIV infection prevalence, laboratories cannot do initial as well as follow-up smear examinations. In Botswana the proportion of smear-positive TB cases declined to 40% in 1992, but the overall proportion of patients who had smears performed had declined (52% in 1992). The multiple regimens in use cause confusion and nonadherence to guidelines. Nonadherence is the major risk factor for the emergence of drug resistance, and low completion rates are the most obvious signs of inadequate control programs. Alternative approaches mean ensuring high completion rates and using the most effective drugs. Regarding diagnosis, research might show that the number of smears could be reduced depending on the initial reading. There is no reason why a rifampicin-based short-course regimen could not replace the multiple regimens now in use. Rifampicin-containing regimens of 62-78 doses given intermittently have been effective and are suitable for use within a DOT program. For prevention of drug resistance, only pills combining different drugs should be used and rifampicin should be limited to the treatment of TB and leprosy.^ieng