Cholera outbreak caused by drinking lake water contaminated with human faeces in Kaiso Village, Hoima District, Western Uganda, October 2015.

BACKGROUND: On 12 October 2015, a cholera outbreak involving 65 cases and two deaths was reported in a fishing village in Hoima District, Western Uganda. Despite initial response by the local health department, the outbreak persisted. We conducted an investigation to identify the source and mode of transmission, and recommend evidence-led interventions to control and prevent cholera outbreaks in this area. METHODS: We defined a suspected case as the onset of acute watery diarrhoea from 1 October to 2 November 2015 in a resident of Kaiso Village. A confirmed case was a suspected case who had Vibrio cholerae isolated from stool. We found cases by record review and active community case finding. We performed descriptive epidemiologic analysis for hypothesis generation. In an unmatched case-control study, we compared exposure histories of 61 cases and 126 controls randomly selected among asymptomatic village residents. We also conducted an environmental assessment and obtained meteorological data from a weather station. RESULTS: We identified 122 suspected cases, of which six were culture-confirmed, 47 were confirmed positive with a rapid diagnostic test and two died. The two deceased cases had onset of the disease on 2 October and 10 October, respectively. Heavy rainfall occurred on 7-11 October; a point-source outbreak occurred on 12-15 October, followed by continuous community transmission for two weeks. Village residents usually collected drinking water from three lakeshore points - A, B and C: 9.8% (6/61) of case-persons and 31% (39/126) of control-persons were found to usually use point A, 21% (13/61) of case-persons and 37% (46/126) of control-persons were found to usually use point B (OR = 1.8, 95% CI: 0.64-5.3), and 69% (42/61) of case-persons and 33% (41/126) of control-persons were found to usually use point C (OR = 6.7; 95% CI: 2.5-17) for water collection. All case-persons (61/61) and 93% (117/126) of control-persons reportedly never treated/boiled drinking water (OR = ∞, 95% CI Fisher: 1.0 - ∞). The village's piped water system had been vandalised and open defecation was common due to a lack of latrines. The lake water was found to be contiminated due to a gully channel that washed the faeces into the lake at point C. CONCLUSIONS: This outbreak was likely caused by drinking lake water contaminated by faeces from a gully channel. We recommend treatment of drinking water, fixing the vandalised piped-water system and constructing latrines.

Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.

Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses.

Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment.

SETTING: Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. OBJECTIVE: To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. DESIGN: An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. RESULTS: Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. CONCLUSION: Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials.

Can lay community health workers be trained to use diagnostics to distinguish and treat malaria and pneumonia in children? Lessons from rural Uganda.

OBJECTIVE: To determine the competence of community health workers (CHWs) to correctly assess, classify and treat malaria and pneumonia among under-five children after training. METHODS: Consultations of 182 under-fives by 14 CHWs in Iganga district, Uganda, were observed using standardised checklists. Each CHW saw 13 febrile children. Two paediatricians observed CHWs' assessment, classification and prescription of treatment, while a laboratory scientist assessed CHW use of malaria rapid diagnostic tests (RDTs). The validity of CHWs' use of RDTs to detect malaria and respiratory timers to diagnose pneumonia was estimated using a laboratory scientist's RDT repeat reading and a paediatrician's repeat count of the respiratory rate, respectively. RESULTS: From the 182 consultations, overall CHWs' performance was adequate in taking history (97%), use (following procedures prior to reading result) of timers (96%) and use of RDTs (96%), but inadequate in classification (87%). Breath readings (classified as fast or normal) were 85% in agreement with the paediatrician (κ = 0.665, P < 0.001). All RDT readings were in agreement with those obtained by the laboratory scientist. Ninety-six per cent (85/89) of children with a positive RDT were prescribed an antimalarial drug, 40% (4/10) with fast breathing (gold standard) were prescribed an antibiotic and 91% (48/53) with both were prescribed both medicines. CONCLUSION: Community health workers can be trained to use RDTs and timers to assess and manage malaria and pneumonia in children. We recommend integration of these diagnostics into community case management of fever. CHWs require enhanced practice in counting respiratory rates and simple job aides to enable them make a classification without thinking deeply about several assessment results.

Implementing Integrated Disease Surveillance and Response: Four African countries' experience, 1998-2005.

The Integrated Disease Surveillance and Response (IDSR) strategy was developed by the Africa Regional Office (AFRO) of the World Health Organisation (WHO) and proposed for adoption by member states in 1998. The goal was to build WHO/AFRO countries' capacity to detect, report and effectively respond to priority infectious diseases. This evaluation focuses on the outcomes in four countries that implemented this strategy. Major successes included: integration of the surveillance function of most of the categorical disease control programmes; implementation of standard surveillance, laboratory and response guidelines; improved timeliness and completeness of surveillance data and increased national-level review and use of surveillance data for response. The most challenging aspects were: strengthening laboratory networks; providing regular feedback and supervision on surveillance and response activities; routine monitoring of IDSR activities and extending the strategy to sub-national levels.

The data for decision making project: assessment of surveillance systems in developing countries to improve access to public health information.

OBJECTIVE: By using timely, high-quality information, ministries of health can identify and address priority health problems in their populations more effectively and efficiently. The Data for Decision Making (DDM) project developed a conceptual model for a data-driven health system. This model included a systematic methodology for assessing access to information to be used as a basis for improvement in national health surveillance systems. STUDY DESIGN AND METHODS: The DDM surveillance assessment methodology was applied to six systems in five countries by staff from the US Centers for Disease Control and Prevention (CDC). Ministry of health personnel at national, regional, district and local levels were interviewed using either informal conversation or an interview guide approach, and their methods for collecting and using data were reviewed. Attributes of timeliness, accuracy, simplicity, flexibility, acceptability and usefulness were examined. Problems and their underlying causes were identified. RESULTS: The problems preventing decision makers from having access to information are many and complex. The assessments identified no fewer than eight problem areas that impeded decision makers' access to information. The most common deficiencies were concerning the design of the system, ongoing training of personnel and dissemination of data from the system. CONCLUSIONS: To improve the availability of information to public health decision makers, it is recommended that: (a) surveillance system improvement begins with a thorough evaluation of existing systems using approaches outlined by the CDC and the Health Metric Network of the World Health Organization; (b) evaluations be designed to identify specific causes of these deficiencies; (c) interventions for improving systems be directly linked to results of the evaluations; and (d) efforts to improve surveillance systems include sustained attention to underlying issues of training and staff support. The assessment tool presented in this report can be used to facilitate this process.

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.

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.

Efficacy of patient-delivered partner medication in the treatment of sexual partners in Uganda.

BACKGROUND: Patient-based partner referral (PBPR), which is the main method for treating sexual partners of patients with sexually transmitted diseases (STDs), has limited effectiveness. GOAL: The authors compared the efficacy of PBPR with patient-delivered partner medication (PDPM) among patients attending the Mulago STD clinic in Kampala, Uganda. STUDY DESIGN: A total of 383 patients (187 women, 196 men) with STDs were randomized to the PBPR or PDPM group. The proportion of sexual partners treated in either group was compared using the chi-square statistic by intention to treat for partners whose follow-up status was unknown. RESULTS: The two groups had similar background characteristics. Of the 237 partners elicited, 176 (74%) were reported treated in the PDPM group. In the PBPR group, in which 234 partners were elicited, 79 (34%) were referred to the treatment clinic. This difference was statistically significant (risk ratio [RR], 2.44; 95% CI, 1.95-3.07; P < 0.001). Furthermore, PDPM was more effective than PBPR for women and for casual partners for whom PBPR is considered difficult. For women, 86 of 103 partners in the PDPM group were reported treated, compared with 23 of 104 partners in the PBPR group (RR, 4.55; 95% CI, 2.92-7.08; P < 0.001). For casual partners, 18 of 51 (34%) were reported treated in the PDPM group, compared with only three of 45 partners (7%) who were referred in the PBPR group (RR, 1.43; 95% CI, 1.40-2.65; P < 0.01). CONCLUSION: Patient-delivered partner medication is more effective than patient-based partner referral in the treatment of sexual partners.

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.

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.

Factors influencing sexual partner referral for sexually transmitted diseases in Uganda.

BACKGROUND AND OBJECTIVE: Patient-based partner referral has limited effectiveness. We studied factors associated with sexual partner referral among patients with sexually transmitted diseases (STDs) with a view of suggesting remedial action. GOAL: To examine the role of psychosocial variables vis-a-vis other variables in predicting sexual partner referral. STUDY DESIGN: A cross-sectional interview survey with 507 patients with STDs at an STD clinic in Kampala, Uganda. Multivariate analyses were used to identify independent predictors of sexual partner referral. RESULTS: Forty-two percent of the 599 partners elicited were referred. The independent factors that favored sexual partner referral were examined in the laboratory (adjusted odds ratio [AOR] 2.20, 95% confidence interval [CI] 1.20-4.05): psychosocial variables of intention (likelihood of referring the partner) (AOR 4.60, CI 1.58-13.36), self-efficacy (partner referral being easy) (AOR 3.22, CI 1.36-7.66), having a positive attitude toward partner referral (AOR 1.19, CI 1.06-1.33), and previous success in having referred a partner (AOR 9.78, CI 2.90-33.04). Other variables, such as age, sex, marital status, employment, and type of partner, that were significant on univariate analysis were not significant after multivariate analysis. CONCLUSION: By providing interventions to change the psychosocial variables, there is a high chance of improving compliance with sexual partner referral.

PIP: This study examined the role of psychosocial variables versus other variables in predicting sexual partner referral. Multivariate analyses were employed to identify independent predictors of sexual partner referral among 507 patients with sexually transmitted diseases in Kampala, Uganda. The study, which was carried out from May 1 to August 31, 1998, indicated that 42% of the 599 partners elicited were referred. The independent factors that favored sexual partner referral were examined in the laboratory and were 1) psychosocial variables of intention (likelihood of referring the partner); 2) self-efficacy (partner referral being easy), having a positive attitude toward partner referral; and 3) previous success in having referred a partner. Other variables, such as age, sex, marital status, employment, and type of partner, were no longer significant after the multivariate analysis was conducted. This study demonstrated that patient referral was mainly influenced by psychosocial variables compared to sociodemographic, disease-based, or type of partner variables. Thus, improvement of compliance with sexual partner referral should focus on interventions that change these psychosocial variables.

Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. The Uganda-Case Western Reserve University Research Collaboration.

Anergy testing has been used as an adjunct to tuberculin testing for assessing M. tuberculosis (MTB) infection and indications for isoniazid preventive therapy in HIV-infected persons. We examined factors associated with the stability of skin test responses to purified protein derivative (PPD) and candida antigens in a cohort of HIV-infected adults followed prospectively in a tuberculosis preventive therapy trial in Uganda. PPD-positive and anergic subjects in the placebo arms of the preventive therapy study underwent repeat skin testing and immunologic testing including measurement of MTB culture filtrate (CF)-stimulated interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels in whole-blood culture supernatants. Anergy was present in 27% of 4,058 HIV-infected subjects screened for the tuberculosis preventive therapy trial compared with 10% of 682 HIV-non-infected persons. On follow-up testing of enrolled subjects, 42% of 139 initially anergic subjects were no longer anergic; two thirds of these had PPD reactions >= 5 mm. Stability of anergy was associated with intercurrent opportunistic infections and AIDS-associated dermatitis at baseline. Thirty-five percent of 313 subjects with an initial positive PPD had a negative PPD test at follow-up, 26% of whom had a positive candida skin test at the same time as the negative PPD test. Baseline MTBCF-stimulated IFN-gamma levels were significantly higher among PPD-positive subjects who remained PPD-positive than in those who were falsely negative. We conclude first that anergy is unstable and second that anergy testing is unreliable in identifying HIV-infected adults who are not infected with MTB and should not be used routinely for this purpose in assessing indications for isoniazid preventive therapy.

Comparison of three composite compliance indices in a trial of self-administered preventive therapy for tuberculosis in HIV-infected Ugandan adults. Uganda-Case Western Reserve University Research Collaboration.

Compliance with tuberculosis preventive therapy in a randomized placebo-controlled trial in 2736 HIV-infected Ugandans was measured using urinary isoniazid metabolite testing, clinic attendance, and self-report. Overall, 77% of urine tests were positive, subjects kept 85% of their scheduled visits while on therapy, and 69% reportedly never forgot to take their medication. Different strategies were used for constructing three composite compliance indices in active arms: (1) an unweighted index of the summed scores on scaled compliance measures; (2) a weighted index using weights obtained from a survey of experts on tuberculosis; and (3) a statistically weighted index using principal components analysis. Composite indices were evaluated for reliability, validity, and practical utility. Understanding of the regimen, study arm, subsequent follow-up, tuberculosis status, and urine spot-check result were associated with composite compliance scores. The unweighted index in this study performed as well as the weighted indices.

Clinical course of human immunodeficiency virus type 1 associated pulmonary tuberculosis during short-course antituberculosis therapy.

To describe the clinical response to antituberculosis therapy in HIV-1 disease, 49 HIV-1 positive Ugandan adults (mean age 29.4 years; 68% men) with active pulmonary tuberculosis (PTB) were studied in a trial of rifampicin containing short-course antituberculosisis regimens. At presentation, 18 patients were PPD non-reactors (PPD skin test induration < 2mm), ten patients (20%) had non-cavitary lung disease. The mean CD4 lymphocyte count at presentation was 339/microliters (+/- SD 275). Among patients with abnormal baseline clinical values, the median time to resolution of fever, weight gain of 10%, increase of haemoglobin to 10g/dl and of Karnofsky performance score (KPS) to 80 occurred before sputum smear and culture conversion. Short-term survival was associated with: baseline lymphocytes < 1200/microliters, (Odds ratio (OR) 17.5), CD4+ lymphocytes < 200/microliters (OR 9.8), cavitary lung disease, (OR 0.6), atypical chest radiograph, (OR 6.7), and PPD non-reactivity, (OR 13.5), PPD non-reactivity and non-cavitary disease were associated with significantly lower CD4 lymphocyte counts. Affordable serial measurements parallel the response to therapy and predict survival in HIV-associated PTB.

PIP: Tuberculosis (TB) is the most often seen and serious opportunistic infection in HIV-1-infected individuals in developing countries. Infection with HIV-1 predisposes individuals to TB, both progressive primary and reactivation disease. To describe the clinical response to anti-TB therapy in HIV-1 disease, 49 HIV-1-positive Ugandan adults of mean age 29.4 years with active pulmonary TB (PTB) were studied in a trial of rifampicin containing short-course anti-TB regimens. At presentation, 18 patients were PPD skin test nonreactive, and 39 had cavitary lung disease. The mean CD4 lymphocyte count at presentation was 339/mcl. Among patients with abnormal baseline clinical values, the median time to resolution of fever, weight gain of 10%, increase of hemoglobin to 10 g/dl, and Karnofsky performance score (KPS) to 80 occurred before sputum smear and culture conversion. Short-term survival was associated with baseline lymphocytes of less than 1200/mcl, cavitary lung disease, atypical chest radiograph, and PPD nonreactivity. PPD nonreactivity and noncavitary disease were associated with significantly lower CD4 lymphocyte counts. Study findings demonstrate that the careful monitoring of clinical symptoms and simple, inexpensive, and widely available laboratory markers permit the satisfactory evaluation of early clinical response to anti-TB therapy in HIV-1-infected patients with pulmonary TB.

Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial.

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.

The high prevalence of genital herpes among patients with genital ulcer disease in Uganda.

BACKGROUND: Genital ulcer disease is a risk factor for transmission of human immunodeficiency virus. One-hundred consecutive Ugandan patients (median age, 25 years) with genital ulcer disease were examined to determine the prevalence of genital herpes and its relationship to human immunodeficiency virus seropositivity. GOAL OF THIS STUDY: To improve management, prevention, and control of genital ulcer disease, thus reducing human immunodeficiency virus infections attributable to genital ulcer disease. STUDY DESIGN: This was a prevalence study of genital herpes in a consecutive sample of an urban sexually transmitted disease clinic population. RESULTS: Forty-nine percent (48/98) of the patients had genital herpes (36% by direct fluorescent antigen and 13% by history of recurrent vesicles). There was a trend toward larger lesions in patients who were human immunodeficiency virus seropositive. Twelve percent (11/89) of patients had syphilis, and 30% (30/100) remained sexually active, despite the presence of active genital ulcer disease. Sixty-five percent of 89 patients tested had antibodies to human immunodeficiency virus. CONCLUSIONS: Genital herpes is a common cause of genital ulcer disease in patients attending sexually transmitted disease clinics in Uganda, and herpes ulcers may be more extensive among those who are infected with human immunodeficiency virus.