Gender differences in the clinical diagnosis of tuberculous lymphadenitis—a hospital-based study from Central India

SummaryObjectiveTuberculous lymphadenitis can be difficult to diagnose clinically, and as it is thought to be more common in females, we describe here the clinical characteristics of cervical tuberculous lymphadenitis in men and women and compare this with cytology to assess their diagnostic value.MethodsTwo hundred and nineteen patients with tuberculous lymphadenitis, aged 14 years or more, who presented with a neck mass to the Department of Pathology, Ujjain Hospital, Ujjain, India were included in the study. The presenting clinical symptoms and signs were compared between men and women and with the cytology of fine needle aspirates from the lymph nodes.ResultsSeventy-five percent of the patients were aged between 14 and 35 years, with a male to female ratio of 1:2.1. One or more constitutional symptoms were present in 56.6% of patients on presentation. There were more men with clinical symptoms than women. Fever was the most common manifestation in both gender groups. Fever for more than 30 days, cough, weight loss, and night sweats were significantly more common in men. On cytology, necrotic granulomas were found to be associated with constitutional symptoms.ConclusionsConstitutional symptoms were more frequently reported by men than by women and showed a correlation with necrotic granulomas on cytology

Immunohistochemical diagnosis of abdominal and lymph node tuberculosis by detecting Mycobacterium tuberculosis complex specific antigen MPT64

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the diagnostic potential of immunohistochemistry using an antibody to the secreted mycobacterial antigen MPT64, in abdominal and lymph node tuberculosis.</p> <p>Methods</p> <p>We used formalin-fixed histologically diagnosed abdominal tuberculosis (n = 33) and cervical tuberculous lymphadenitis (n = 120) biopsies. These were investigated using a combination of Ziehl-Neelsen method, culture, immunohistochemistry with an antibody to MPT64, a specific antigen for <it>Mycobacterium tuberculosis</it> complex organisms. Abdominal and cervical lymph node biopsies from non-mycobacterial diseases (n = 50) were similarly tested as negative controls. Immunohistochemistry with commercially available anti-BCG and nested PCR for IS6110 were done for comparison. Nested PCR was positive in 86.3% cases and the results of all the tests were compared using nested PCR as the gold standard.</p> <p>Results</p> <p>In lymph node biopsies, immunohistochemistry with anti-MPT64 was positive in 96 (80%) cases and 4 (12.5%) controls and with anti-BCG 92 (76.6%), and 9 (28%) respectively. The results for cases and controls in abdominal biopsies were 25 (75.7%) and 2 (11.1%) for anti-MPT64 and 25 (75.7%) and 4 (22%) for anti-BCG. The overall sensitivity, specificity, positive and negative predictive values of immunohistochemistry with anti-MPT64 was 92%, 97%, 98%, and 85%, respectively while the corresponding values for anti-BCG were 88%, 85%, 92%, and 78%.</p> <p>Conclusion</p> <p>Immunohistochemistry using anti-MPT64 is a simple and sensitive technique for establishing an early and specific diagnosis of <it>M. tuberculosis</it> infection and one that can easily be incorporated into routine histopathology laboratories.</p

Smear microscopy and culture conversion rates among smear positive pulmonary tuberculosis patients by HIV status in Dar es Salaam, Tanzania

Tanzania ranks 15th among the world's 22 countries with the largest tuberculosis burden and tuberculosis has continued to be among the major public health problems in the country. Limited data, especially in patients co infected with HIV, are available to predict the duration of time required for a smear positive pulmonary tuberculosis patient to achieve sputum conversion after starting effective treatment. In this study we assessed the sputum smear and culture conversion rates among HIV positive and HIV negative smear positive pulmonary tuberculosis patients in Dar es Salaam The study was a prospective cohort study which lasted for nine months, from April to December 2008 A total of 502 smear positive pulmonary tuberculosis patients were recruited. HIV test results were obtained for 498 patients, of which 33.7% were HIV positive. After two weeks of treatment the conversion rate by standard sputum microscopy was higher in HIV positive(72.8%) than HIV negative(63.3%) patients by univariate analysis(P = 0.046), but not in multivariate analysis. Also after two weeks of treatment the conversion rate by fluorescence microscopy was higher in HIV positive (72.8%) than in HIV negative(63.2%) patients by univariate analysis (P = 0.043) but not in the multivariate analysis. The conversion rates by both methods during the rest of the treatment period (8, 12, and 20 weeks) were not significantly different between HIV positive and HIV negative patients.With regards to culture, the conversion rate during the whole period of the treatment (2, 8, 12 and 20 weeks) were not significantly different between HIV positive and HIV negative patients.\ud Conversion rates of standard smear microscopy, fluorescence microscopy and culture did not differ between HIV positive and HIV negative pulmonary tuberculosis patients

Genetic profile of Mycobacterium tuberculosis and treatment outcomes in human pulmonary tuberculosis in Tanzania

Information on the different spoligotype families of Mycobacterium tuberculosis in Tanzania is limited, and where available is restricted to small geographical areas.  This article describes the genetic profile of M. tuberculosis across Tanzania and suggests how spoligotype families might affect drug resistance and treatment outcomes for smear positive pulmonary tuberculosis patients in Tanzania. In this study conducted from 2006 to 2008, the M. tuberculosis isolates were obtained from samples collected under the routine drug resistance surveillance system. The isolates were from specimens collected from 2001 to 2007, and stored at the Central and Reference Tuberculosis Laboratory in Dar es Salaam. A total of 487 isolates from 23 regions in Tanzania were spoligotyped. However, clinical information for 446 isolates was available. Out of the 487 isolates spoligotyped, 195 (40.0%) belonged to the Central Asian (CAS) family, 84 (17.5%) to the Latin American Mediterranean (LAM) family, 49 (10.1%) to the East-African Indian (EAI) family, and 33 (6.8%) to the Beijing family. Other isolates included 1 (0.2%) for H37Rv, 10 (2.1%) for Haarlem, 4 (0.8%) for S family, 58 (11.9%) for T family and 52 (10.7%) for unclassified.  No spoligotype patterns were consistent with M. bovis. As regards to treatment outcomes, the cure rate was 80% with no significant variation between the spoligotype families.  The overall level of MDR-TB was 2.5% (3/121), with no significant difference between the spoligotype families. All Beijing strains (11.8%, 30/254) originated from the Eastern and Southern zones of the country, of which 80% were from Dar es Salaam.  Isolates from the CAS and T families were reported disproportionately from the Eastern-Southern zone, and EAI and LAM families from the Northern-Lake zones but the difference was not statistically significant. Five isolates were identified as Non-tuberculous Mycobacteria. In conclusion, M. tuberculosis isolates from pulmonary tuberculosis cases in Tanzania were classified mostly within the CAS, LAM, and EAI and T families.  Consistently good treatment outcomes were recorded across the spoligotype families.  The proportion of drug resistance strains was low. The findings also suggest variation of spoligotype families with varying geographical localities within the country. 

Current status of medication adherence and infant follow up in the prevention of mother to child HIV transmission programme in Addis Ababa: a cohort study

<p>Abstract</p> <p>Background</p> <p>Prevention of mother to child HIV transmission (PMTCT) programmes have great potential to achieve virtual elimination of perinatal HIV transmission provided that PMTCT recommendations are properly followed. This study assessed mothers and infants adherence to medication regimen for PMTCT and the proportions of exposed infants who were followed up in the PMTCT programme.</p> <p>Methods</p> <p>A prospective cohort study was conducted among 282 HIV-positive mothers attending 15 health facilities in Addis Ababa, Ethiopia. Descriptive statistics, bivariate and mulitivariate logistic regression analyses were done.</p> <p>Results</p> <p>Of 282 mothers enrolled in the cohort, 232 (82%, 95% CI 77-86%) initiated medication during pregnancy, 154 (64%) initiated combined zidovudine (ZDV) prophylaxis regimen while 78 (33%) were initiated lifelong antiretroviral treatment (ART). In total, 171 (60%, 95% CI 55-66%) mothers ingested medication during labour. Of the 221 live born infants (including two sets of twins), 191 (87%, 95% CI 81-90%) ingested ZDV and single-dose nevirapine (sdNVP) at birth. Of the 219 live births (twin births were counted once), 148 (68%, 95% CI 61-73%) mother-infant pairs ingested their medication at birth. Medication ingested by mother-infant pairs at birth was significantly and independently associated with place of delivery. Mother-infant pairs attended in health facilities at birth were more likely (OR 6.7 95% CI 2.90-21.65) to ingest their medication than those who were attended at home. Overall, 189 (86%, 95% CI 80-90%) infants were brought for first pentavalent vaccine and 115 (52%, 95% CI 45-58%) for early infant diagnosis at six-weeks postpartum. Among the infants brought for early diagnosis, 71 (32%, 95% CI 26-39%) had documented HIV test results and six (8.4%) were HIV positive.</p> <p>Conclusions</p> <p>We found a progressive decline in medication adherence across the perinatal period. There is a big gap between mediation initiated during pregnancy and actually ingested by the mother-infant pairs at birth. Follow up for HIV-exposed infants seem not to be organized and is inconsistent. In order to maximize effectiveness of the PMTCT programme, the rate of institutional delivery should be increased, the quality of obstetric services should be improved and missed opportunities to exposed infant follow up should be minimized.</p

Promising outcomes of a national programme for the prevention of mother-to-child HIV transmission in Addis Ababa: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Prevention of Mother-to-Child HIV Transmission (PMTCT) is still the most effective intervention in combating new HIV infections. In 2008, revised national PMTCT guidelines that incorporated new policies on HIV counselling and testing, antiretroviral prophylaxis regimen and infant HIV diagnosis came into effect in Ethiopia. In the present study we have examined trends in PMTCT service utilization and assessed the rate of MTCT in relation to policy changes in the national PMTCT programme.</p> <p>Methods</p> <p>Reports from February 2004 to August 2009 were reviewed in 10 sub-cities in Addis Ababa, Ethiopia. The data was collected from May to October 2009.</p> <p>Results</p> <p>The proportion of women who received HIV counselling and testing among new antenatal care attendees increased from 50.7% (95% CI 50.2-51.2) in 2007 to 84.5% (95% CI 84.1-84.9) in 2009 following the shift to routine opt-out testing. Nevertheless, in 2009 only 53.7% of the positive women and 40.7% of their infants received antiretroviral prophylaxis. The HIV prevalence among antenatal attendees decreased significantly from 10.5% in 2004 to 4.6% in 2009 in parallel to the increased number of women being tested. The HIV positive women were over 18 times (RR 18.5, p < 0.0001) more likely to be referred for treatment, care and support in 2009 than in 2004. The proportion of partners tested for HIV decreased by 14% in 2009 compared to 2004, although the absolute number was increasing year by year. Only 10.6% (95% CI 9.9-11.2) of the HIV positive women completed their follow up to infant HIV testing. The cumulative probability of HIV infection among babies on single dose nevirapine regimen who were tested at >=18 months was 15.0% (95% CI 9.8-22.1) in 2007, whereas it was 8.2% (95% CI 5.55-11.97) among babies on Zidovudine regimen who were tested at >=45 days in 2009.</p> <p>Conclusion</p> <p>The paper demonstrates trends in PMTCT service utilization in relation to changing policy. There is marked improvement in HIV counselling and testing service utilization, especially after the policy shift to routine opt-out testing. However, despite policy changes, the ARV prophylaxis uptake, the loss to follow up and the partner testing have remained unchanged across the years. This should be a matter of immediate concern and a topic for further research.</p

Differential expression of mycobacterial antigen MPT64, apoptosis and inflammatory markers in multinucleated giant cells and epithelioid cells in granulomas caused by Mycobacterium tuberculosis

The development of granulomas is a major histopathological feature of tuberculosis. Very little information is available concerning the physiology and functions of different cell types in the tuberculous granulomas. The aim of this study was to compare the epithelioid cells (ECs) and multinucleated giant cells (MGCs) in the granulomas caused by Mycobacterium tuberculosis complex organisms. Lymph node biopsies from 30 cases of lymphadenitis were studied for expression of the secreted mycobacterial protein MPT64, caspase 3 as a marker of apoptosis, apoptosis-related proteins (Fas Ligand, Fas and Bax) and inflammatory cytokines (interleukin-10, transforming growth factor-β (TGF-β), tumour necrosis factor-α and interferon-γ) by immunohistochemistry. MGCs more often contained M. tuberculosis secretory antigen MPT64 (p < 0.001) and expressed more TGF-β (p = 0.004) than ECs. The total number of apoptotic MGCs was higher than the number of apoptotic ECs (p = 0.04). Interestingly, there was a significant negative correlation between apoptosis and MPT64 expression in MGCs (r = −0.569, p = 0.003), but not in ECs, implying that the heavy antigen load would lead to inhibition of apoptosis in these cells. When compared with ECs, higher percentage of MGCs expressed Fas Ligand and Fas (p < 0.004). The role of MGCs may thus be different from surrounding ECs and these cells by virtue of higher mycobacterial antigen load, more TGF-β and reduced apoptosis may contribute towards persistence of infection

Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma (IFN-γ) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON^®-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.</p> <p>Methods</p> <p>481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.</p> <p>Results</p> <p>The QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST ≥ 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-γ responses were comparable at start (mean 6.13 IU/ml ± SD 3.99) and after three months (mean 5.65 IU/ml ± SD 3.66) and 15 months (mean 5.65 IU/ml ± SD 4.14), (p > 0.05).</p> <p>Conclusion</p> <p>Only one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.</p

Tuberculosis case-finding through a village outreach programme in a rural setting in southern Ethiopia: community randomized trial

OBJECTIVE: To ascertain whether case-finding through community outreach in a rural setting has an effect on case-notification rate, symptom duration, and treatment outcome of smear-positive tuberculosis (TB). METHODS: We randomly allocated 32 rural communities to intervention or control groups. In intervention communities, health workers from seven health centres held monthly diagnostic outreach clinics at which they obtained sputum samples for sputum microscopy from symptomatic TB suspects. In addition, trained community promoters distributed leaflets and discussed symptoms of TB during house visits and at popular gatherings. Symptomatic individuals were encouraged to visit the outreach team or a nearby health facility. In control communities, cases were detected through passive case-finding among symptomatic suspects reporting to health facilities. Smear-positive TB patients from the intervention and control communities diagnosed during the study period were prospectively enrolled. FINDINGS: In the 1-year study period, 159 and 221 cases of smear-positive TB were detected in the intervention and control groups, respectively. Case-notification rates in all age groups were 124.6/10(5) and 98.1/10(5) person-years, respectively (P = 0.12). The corresponding rates in adults older than 14 years were 207/10(5) and 158/10(5) person-years, respectively (P = 0.09). The proportion of patients with >3 months' symptom duration was 41% in the intervention group compared with 63% in the control group (P<0.001). Pre-treatment symptom duration in the intervention group fell by 55-60% compared with 3-20% in the control group. In the intervention and control groups, 81% and 75%, respectively of patients successfully completed treatment (P = 0.12). CONCLUSION: The intervention was effective in improving the speed but not the extent of case finding for smear-positive TB in this setting. Both groups had comparable treatment outcomes

Injuries in Khartoum state, the Sudan: a household survey of incidence and risk factors

Low- and middle-income countries have a higher burden of fatal and non-fatal injuries. The lack of evidence-based information hampers efforts for injury prevention. The aim of this study was to calculate non-fatal injury incidence rates and to investigate causes and risk factors for non-fatal injuries in Khartoum state. Information was gathered in a community-based survey using a stratified two-stage cluster sampling technique. Methods of data collection were face-to-face interviews during October and November 2010. The total number of individuals included was 5661, residing in 973 households. The overall injury incidence rate was 82.0/1000 person-years-at-risk. The three leading causes were falls, mechanical forces and road traffic crashes. Low socio-economic status was a risk factor for injuries in urban areas. Males had a significantly higher risk of being injured in both urban and rural areas. Our findings can contribute to the planning of prevention programmes