Incidence of tuberculous infection in a TB-endemic city.

Current metrics for TB transmission include TB notifications, disease mortality, and prevalence surveys. These metrics are helpful to national TB programs to assess the burden of disease, but they do not directly measure incident infection in the community.To estimate incidence of Mycobacterium tuberculosis infection in Kampala, Uganda, we performed a prospective cohort study between 2014 and 2017 which enrolled of 1,275 adult residents without signs of tuberculous infection (tuberculin skin test [TST] <5 mm and no signs of TB disease) and followed them for conversion of TST at 1 year.During follow-up, 194 participants converted the TST and 158 converted by one year. The incidence density of TST conversion was 13.2 conversions/100 person-year (95% CI 11.6-15.1), which corresponds to an annual cumulative incidence of tuberculous infection of 12.4% (95% CI 10.7-14.3). Cumulative incidence was greater among older participants and among men. Among participants who reported prior exposure to TB cases, the cumulative risk was highest among those reporting exposure during follow-up.The high annual incidence of infection suggests that residents of Kampala have adequate contact for infection with undetected, infectious cases of TB as they go about their daily lives..

A randomized trial of punctuated antiretroviral therapy in Ugandan HIV-seropositive adults with pulmonary tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/µL.

BACKGROUND: Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4⁺ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression. METHODS: We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/µL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4⁺ T-cell counts of < 250 cells/µL, AIDS, or death. RESULTS: Intervention and comparison arms had similar median CD4⁺ counts (517 and 534 cells/µL, respectively) and HIV RNA levels (4.6 and 4.7 log10 copies/µL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis. CONCLUSIONS: Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4⁺T-cell counts of >350 cells/µL was safe and associated with clinical benefits.

Reorganization of the axon membrane in demyelinated peripheral nerve fibers: morphological evidence.

Cytochemical staining of demyelinated peripheral axons revealed two types of axon membrane organization, one of which suggests that the demyelinated axolemma acquires a high density of sodium channels. Ferric ion-ferrocyanide stain was confined to a restricted region of axon membrane at the beginning of a demyelinated segment or was distributed throughout the demyelinated segment of axon. The latter pattern represents one possible morphological correlate of continuous conduction through a demyelinated segment and suggests a reorganization of the axolemma after demyelination.

Active case finding of undetected tuberculosis among chronic coughers in a slum setting in Kampala, Uganda.

SETTING: Kisenyi slum in peri-urban Kampala, Uganda. OBJECTIVES: Using chronic cough (> or = 2 weeks) inquiry as a screening tool to identify undetected smear-positive tuberculosis (TB) cases and to describe the characteristics of smear-positive TB cases detected by active case finding. DESIGN: A house-to-house survey was conducted in five randomly selected villages in Kampala between June and August 2005. A sample of households was visited; adults aged > or = 15 years were consecutively interviewed to identify those with chronic cough. Three sputum specimens were collected and examined by smear microscopy. RESULTS: Among 930 individuals, we identified 189 (20%) chronic coughers. Of these, we found 33 (18%) undiagnosed smear-positive cases. The newly detected cases had an even sex distribution (P = 0.47), a median age of 30 years, a median cough duration of 1 month and 55% had acid-fast bacilli 1+ sputum smear grade. CONCLUSION: These findings suggest that active case finding could supplement DOTS to yield additional smear-positive TB cases, lead to early diagnosis and thus shorten the duration of infectiousness before effective chemotherapy is initiated. In communities such as Kisenyi, this is a feasible strategy that may prove useful for TB control, but its cost-effectiveness needs to be evaluated. Early health care seeking for cough should be emphasized.

Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda.

BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.

Performance of the QuantiFERON®-TB Gold In-Tube assay in tuberculin skin test converters: a prospective cohort study.

OBJECTIVE: To investigate diagnostic agreement of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high tuberculosis (TB) burden setting. SETTING AND DESIGN: We performed a case-cohort study from 2014 to 2016 in Uganda among residents who were not infected with Mycobacterium tuberculosis. Participants were followed up for 1 year, when they were retested to determine TST conversion. All TST converters and a random sample of participants from baseline were offered QFT-GIT testing. RESULTS: Of 368 enrolled participants, 61 (17%) converted their TST by 1 year. Among 61 converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of 307 participants with a persistent negative TST, 48 were tested using QFT-GIT, 83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was moderate (κ = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm had a higher proportion of concordant QFT-GIT results (79%) than converters with increments of 10-14.9 mm (52%). CONCLUSION: Concordance between TST and QFT-GIT was moderate among TST converters in this urban African population. These findings call for improved tests that more accurately measure conversion to tuberculous infection.

Characterization of penicillin intermediate serotypes of Streptococcus pneumoniae carried by human immunodeficiency virus-infected adults and healthy children in Uganda.

There are little data on the genetic relatedness between antibiotic-resistant pneumococcal isolates colonizing the Ugandan population. Penicillin-intermediate pneumococci of serogroups or serotypes rarely or not previously reported as being penicillin nonsusceptible were selected out of 166 isolates representing 26 capsular serogroups or serotypes isolated from Ugandan children in 1995 and human immunodeficiency virus (HIV) infected Ugandan adults in 2004-2005. Pairs of penicillin-intermediate pneumococci of the same serogroup or serotype present in both patient populations were characterized further by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Seven such pairs of isolates were found and included serogroups 7, 11, 15B/C, and 16 as well as serotypes 13, 21, and 35B. PFGE of these seven pairs showed no clonality between serogroups or serotypes, and clonality only within serogroup 11 and serotype 13. MLST of the 14 individual isolates revealed 13 different sequence types (STs), 11 of which had not previously been recorded. Comparisons with all known STs revealed that most of these strains were related only to strains of the same serotype in other countries, with these related strains frequently also being penicillin intermediate. These findings suggest that penicillin nonsusceptibility in Uganda is likely due to the introduction of antibiotic-resistant pneumococcal clones into Uganda rather than development of resistance within the country.

Elevated HIV seroprevalence and risk behavior among Ugandan TB suspects: implications for HIV testing and prevention.

OBJECTIVES: Voluntary counseling and testing (VCT) for the human immunodeficiency virus (HIV) is recommended for persons treated for tuberculosis (TB). Opportunities to diagnose HIV may be missed by limiting HIV testing to only persons diagnosed with TB. Among TB suspects in Uganda, we determined HIV prevalence, risk behaviors, and willingness to refer family for VCT. METHODS: Consenting adult patients presenting for evaluation at a referral TB clinic received same-day VCT. TB diagnosis data were abstracted from clinical records. RESULTS: Among 665 eligible patients, 565 (85%) consented to VCT. Among these, 238 (42%) were HIV-positive. Of the HIV-infected patients, 37% had received a non-TB diagnosis. HIV seroprevalence was higher in patients with a non-TB diagnosis (49%) than those diagnosed with TB (39%) (P = 0.02). Fewer than 6% of HIV-infected patients reported always using condoms with sexual partners. The majority of patients (86%) reported being 'very willing' to refer family members for VCT. CONCLUSIONS: Over 35% of HIV-infected cases in our population would have been undetected if HIV testing was limited to cases with diagnosed TB. The high HIV seroprevalence in both TB and non-TB cases merits HIV testing for all patients evaluated at TB clinics. HIV-infected TB suspects reporting high-risk behavior are at risk for HIV transmission, and should receive risk-reduction counseling.

Comparison of intermittent ethambutol with rifampicin-based regimens in HIV-infected adults with PTB, Kampala.

BACKGROUND: The human immunodeficiency virus (HIV) is a key factor responsible for the high rates of tuberculosis (TB) in sub-Saharan Africa. Treatment of TB with rifampicin (R, RMP) containing short-course regimens is highly effective in HIV-infected adults. We conducted a study to compare the efficacy and safety of intermittent ethambutol (E, EMB) with two RMP-containing regimens to treat pulmonary TB in HIV-infected patients. SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. DESIGN: This was a prospective cohort compared to two non-randomised control groups. The study group and the two control arms were treated with 2 months of isoniazid (H), RMP, pyrazinamide (Z) and EMB followed by 6 E3H3 for the study group and 4HR or 6HR for controls. RESULTS: Between April 1993 and March 2000, 136 patients were enrolled in the 2EHRZ/E3H3 arm, 147 in the 2EHRZ/4HR arm and 266 in the 2EHRZ/6HR arm. The relapse rate was 18.2 per 100 person-years observation (PYO) for the study regimen compared to 9.7/100 PYO (P = 0.0063) and 4.8/100 PYO (P = 0.0001) in patients treated with 2 EHRZ/4HR or 2EHRZ/6HR, respectively. CONCLUSION: The 2EHRZ/6E3H3 regimen is safe and effective but has a significant risk of relapse.

Tuberculosis infection among health care workers in Kampala, Uganda.

Nosocomial tuberculosis (TB) is a serious problem in sub-Saharan Africa due to the absence of protective measures for health care workers (HCWs). To determine the prevalence of TB infection among HCWs in Kampala, Uganda, a cross-sectional study was conducted between June and August 2001. A tuberculin skin test (TST) survey was conducted among 396 HCWs from three hospitals within Kampala, The prevalence of TST > or = 10 mm was 57%. Age and department of employment were associated with TST > or = 10 mm, while occupation and BCG status were not. Health care workers in Kampala, Uganda, have a high prevalence of latent TB infection.

Patients perceived stigma associated with community-based directly observed therapy of tuberculosis in Uganda.

OBJECTIVE: To assess whether linkage of tuberculosis (TB) and HIV/AIDS increases the perception of stigma among TB patients on Community-Based Directly Observed Therapy (CB-DOT) compared to similar TB patients on self-administered therapy (SAT). DESIGN: A Cross-sectional study. SETTING: Kiboga (CB-DOT) and Mubende (SAT) districts, Uganda in 2000. SUBJECTS: One hundred and five tuberculosis patients on CB-DOT and 202 patients on SAT. One hundred and twenty one (39%) of these patients agreed to be tested for HIV. RESULTS: Patients on CB-DOT and patients on SAT were similar on most of the domains used to assess stigma associated with a TB diagnosis, except for the domain of TB diagnosis and general belief that TB and HIV/AIDS are linked. Patients on CB-DOT were more likely to believe that neighbours knew they had TB compared to patients on SAT (91% vs. 62%, p < 0.001), but the groups did not differ in their perception that neighbours thought they have HIV because of TB (46% vs. 46%, p = 0.954). HIV prevalence was similar in both groups. CONCLUSION: The study demonstrates that TB patients on CB-DOT did not differ from SAT patients in their perception of stigma as a result of TB. Therefore, HIV-related stigma may not limit wide implementation of CB-DOT in countries like Uganda.

Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda.

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.

Placebo-controlled trial of prednisone in advanced HIV-1 infection.

OBJECTIVE: To examine the safety and the immunologic and virologic consequences of corticosteroid use in HIV-1 infection. METHODS: A randomized, double-blinded, placebo-controlled trial of corticosteroid administration in 41 patients with advanced HIV-1 infection. Patients had a baseline median CD4 cell count of 131 x 10(6) cells/l at enrollment and 85% had a history of opportunistic infection. All but one of the patients had been taking stable antiretroviral regimen, including a protease inhibitor in 36, for a median duration of 158 days. Patients were randomized to 8 weeks of prednisone 0.5 mg/kg daily or placebo. RESULTS: No AIDS-defining events occurred; two patients in each group developed oral candidiasis, and two patients on prednisone developed mild herpes simplex flares. None who developed oral candidiasis or herpes simplex was receiving prophylaxis and each responded promptly to therapy. In the prednisone group, two patients developed hyperglycemia and one diabetic increased insulin requirements. CD4 cell counts and plasma HIV-1 RNA levels did not change, but plasma tumor necrosis factor alpha levels and CD38+ CD8+ cells decreased significantly in those taking prednisone. CONCLUSION: Short-term prednisone administration is well tolerated and reasonably safe in advanced HIV-1 disease and decreases immune activation without effects on HIV-1 RNA levels or CD4 cell counts. These results suggest that, in stable HIV-1 disease, these immune activation markers are more likely consequences of but not inducers of HIV-1 replication.

Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.

BACKGROUND: Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens. METHODS: Three daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo. RESULTS: 6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42-1.07] for 6H, 0.49 (95% CI, 0.29-0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29-0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32-1.16). Treatment of latent tuberculosis infection had no effect on mortality. CONCLUSION: Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.

Withdrawal of steroids after renal transplantation--clinical predictors of outcome.

Withdrawal of steroid therapy in renal transplant recipients is associated with a risk of acute allograft rejection. To define clinical risk factors for rejection associated with steroid withdrawal, we analyzed the clinical characteristics of 107 patients with drawn from steroid therapy at various times after transplantation. Both univariate and multivariate analyses suggested that the timing of steroid withdrawal is an important predictor of steroid withdrawal failure. Withdrawal of steroids was successful in only 13 of 32 patients (41%) in whom prednisone was discontinued shortly after transplantation. In contrast, steroid withdrawal has been successful in 59 of 75 patients (79%) in whom prednisone was discontinued at least 6 months after transplantation. Black race and donor-recipient racial mismatch also were significant predictors of rejection associated with steroid withdrawal. In patients undergoing steroid withdrawal at least 6 months posttransplant, serum creatinine concentration also correlated independently with the risk of rejection. Neither age, sex, HLA match, pretransplant PRA, source of the allograft (cadaver vs. living relative), acute tubular necrosis, nor the presence of diabetes was predictive of the outcome of steroid withdrawal.

An index of symptoms for infection with human immunodeficiency virus: reliability and validity.

The objective of this study was to evaluate the reliability and validity of a brief index to measure symptoms in individuals infected with human immunodeficiency virus (HIV). From an ambulatory clinic that specializes in the care of HIV-infected individuals at a university hospital in northeast Ohio, 148 randomly selected outpatients (predominantly homosexual men) with a broad spectrum of HIV disease were enrolled in a prospective, cohort study. In standard interviews, patients rated the frequency of 36 symptoms related to HIV infection on an ordinal scale from zero (never) to three (daily); these interviews were repeated and outcomes determined every 3 months for one year. Clinical data were abstracted from the medical record with a standard chart review. Using specific criteria, 12 symptoms were selected for the HIV Symptom Index: fatigue, fevers, headache, imbalance, paresthesias, memory loss, cough, nausea, diarrhea, sadness, sleep disturbance, and skin problems. The HIV Symptom score (the sum of frequency ratings for the 12 symptoms) ranged from 0 to 31 with a mean of 9.4 (+/- SD 6.6). The test-retest reliability was high (intraclass correlation coefficient = 0.92) as was the internal consistency (Cronbach's alpha = 0.79). The validity of the index was established with three observations. (1) The HIV Symptom Index makes clinical sense and includes a representative spectrum of symptoms of infection. (2) Symptom Index scores were greater in patients with more advanced disease and in patients who were functionally impaired. (3) The Index was responsive to changes in health as the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Justification for a new cohort study of people aging with and without HIV infection.

This supplement contains a series of papers supporting the justification, design, and implementation of a longitudinal cohort study of an aging HIV-positive and HIV-negative veteran population called the Veterans Aging Cohort Study (VACS). Although the papers cover a wide range of topics and several papers address methodologic issues not unique to a study of aging veterans, all are motivated by a unifying set of assumptions. Specifically: (a) HIV/AIDS is a chronic disease in an aging population; (b) conditions among HIV-positive and -negative patients in care have overlapping etiologies; (c) individuals with pre-existing organ injury are at increased risk for iatrogenic injury; (d) cohort studies are uniquely suited to the study of chronic disease complicated by aging, comorbid conditions, drug toxicities, and substance use/abuse; (e) VACS is well positioned to study HIV as a chronic disease in an aging population.

Public and private providers' quality of care for tuberculosis patients in Kampala, Uganda.

SETTING: The role of the private sector in tuberculosis treatment in developing countries in sub-Saharan Africa is largely unknown. In recent years, many fee-for-service clinics have opened up in Kampala, Uganda. Little is known about the tuberculosis caseload seen in private clinics or the standard of care provided to the patients. OBJECTIVE: To compare the appropriateness of tuberculosis care in private and public clinics, and the extent of the tuberculosis burden handled in the private sector. DESIGN: Cross-sectional survey in private and public clinics treating tuberculosis patients in Kampala, Uganda, during June to August 1999. MEASUREMENTS: Clinics were evaluated for appropriateness of care. This was defined as provision of proper diagnosis (sputum smear microscopy as the primary means of diagnosis), treatment (short-course chemotherapy, with or without directly observed therapy), outcome evaluation (smear microscopy at 6 or 7 months) and case notification in accordance with the Uganda National Tuberculosis and Leprosy Programme. RESULTS: A total of 114 clinics (104 private, 10 public) were surveyed. Forty-one per cent of the private clinics saw three or more new tuberculosis patients each month. None of the public or private clinics met all standards for appropriate tuberculosis care. Only 24% of all clinics adhered to WHO-recommended treatment guidelines. Public clinics, younger practitioners and practitioners with advanced degrees were most likely to provide appropriate care for tuberculosis. CONCLUSION: The private sector cares for many tuberculosis cases in Kampala; however, a new programme that offers continuing medical education is needed to improve tuberculosis care and to increase awareness of national guidelines for tuberculosis care.

Risk factors for adverse drug reactions during thiacetazone treatment of pulmonary tuberculosis in human immunodeficiency virus infected adults.

SETTING: Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda. OBJECTIVE: To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB. DESIGN: Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR). RESULTS: Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02). CONCLUSION: Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

Malnutrition and the severity of lung disease in adults with pulmonary tuberculosis in Malawi.

SETTING: Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To examine the relationship between malnutrition and the severity of lung disease in human immunodeficiency virus (HIV) positive and negative adults with pulmonary tuberculosis (PTB). DESIGN: Cross-sectional study. METHODS: Chest radiographs and anthropometric measurements were obtained and bioelectrical impedance analysis was conducted in sputum-positive patients with pulmonary tuberculosis. Lung disease in chest radiographs was graded as normal, minimal, moderately advanced and far advanced according to a conventional classification system. RESULTS: Among 319 adults with PTB with or without HIV co-infection, body mass index (BMI), fat mass and phase angle were independently associated with increasing severity of lung disease. Multiple logistic regression analyses showed that BMI, fat mass and phase angle were associated with increasing severity of lung disease among 236 HIV-positive adults, when adjusted for sex, age, and plasma HIV load. CONCLUSION: The severity of lung disease in adults with PTB is associated with the extent of malnutrition, as reflected by BMI and body composition studies using bioelectrical impedance analysis.