Designing an operational research TB training program in Zambia.

BACKGROUND: The USAID-funded Eradicate TB Project (ETB) partnered with the National Tuberculosis and Leprosy Control Program (NTLP) to establish an operational research (OR) training program in order to generate local evidence to enhance TB care in Zambia. METHOD: Between 2017 and 2021, healthcare workers (HCWs) from district teams underwent two 10-day intensive training sessions. The program evolved to include a competitive application process and an additional primer workshop on developing feasible research questions. RESULTS: Of the 36 enrollees in the OR training program, 26 (72.2%) completed it, leading to nine OR studies that informed interventions for TB care improvement. Notable achievements include reduced TB mortality, increased pediatric notifications, and enhanced sputum courier systems, with all studies disseminated at national and international conferences, four submitted to peer-reviewed journals, of which three were published. Two studies were replicated by the NTLP at provincial and national levels. CONCLUSIONS: Integrating OR training into TB initiatives is feasible and beneficial. The program's phased execution and adaptive strategies provide valuable insights for similar settings, although challenges in sustainability of mentorship and funding persist. This success underscores the importance of continuous OR capacity strengthening among HCWs in Zambia.

CONTEXTE: Le projet Eradicate TB (ETB) financé par l'USAID s'est associé au programme National de contrôle de la Tuberculose et de la Lèpre (NTLP) pour mettre en place un programme de formation à la recherche opérationnelle (OR), afin de générer des preuves locales pour améliorer les soins de la TB en Zambie. MÉTHODE: Entre 2017 et 2021, des travailleurs de la santé (HCWs) provenant d'équipes de district ont suivi deux sessions de formation intensive de 10 jours. Le programme a évolué pour inclure un processus de candidature concurrentiel et un atelier d'initiation supplémentaire sur l'élaboration de questions de recherche réalisables. RÉSULTATS: Vingt-six (72,2%) des HCW inscrits au programme ont terminé leur formation, ce qui a donné lieu à neuf études de OR qui ont servi de base à des interventions visant à améliorer les soins antituberculeux. Parmi les réalisations notables, citons la réduction de la mortalité due à la TB, l'augmentation des notifications pédiatriques et l'amélioration des systèmes de messagerie des expectorations. Toutes les études ont été diffusées lors de conférences nationales et internationales, quatre ont été soumises à des revues à comité de lecture et trois ont été publiées. Deux études ont été reproduites par le NTLP aux niveaux provincial et national. CONCLUSIONS: L'intégration de la formation OR dans les initiatives de lutte contre la TB est faisable et bénéfique. L'exécution progressive du programme et les stratégies adaptatives fournissent des indications précieuses pour des contextes similaires, bien que les défis liés à la durabilité du mentorat et du financement persistent. Ce succès souligne l'importance d'un renforcement continu des capacités OR parmi les HCW en Zambie.

Scale-up of TB and HIV programme collaborative activities in Zambia - a 10-year review.

OBJECTIVE: To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. METHODS: Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010. RESULTS: The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. CONCLUSIONS: The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).

Population differences in death rates in HIV-positive patients with tuberculosis.

SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

SETTING: Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. OBJECTIVE: To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. DESIGN: Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. RESULTS: A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. CONCLUSION: TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults.

OBJECTIVE: To determine the long-term effect of preventive therapy (PT) for tuberculosis on the rates of tuberculosis, mortality and HIV progression. METHODS: In a randomized controlled trial, 1053 HIV-positive Zambian adults received isoniazid (H) for 6 months, rifampicin plus pyrazinamide (RZ) for 3 months, or a placebo. CD4 percentage, neopterin, absolute lymphocyte count and haemoglobin were measured from enrolment (absolute CD4 cell counts from 12 months after enrolment). Because PT reduced the incidence of tuberculosis, eligible placebo subjects were offered H. Here, tuberculosis and mortality rates are compared in the three original arms (intention to treat) using data beyond the end of the trial (average follow-up 3 years; maximum 7 years). RESULTS: There were 102 cases of tuberculosis and 281 deaths (rates 3.6 and 9.0/100 person-years, respectively). There was no significant difference between the tuberculosis rates in the H and RZ groups at any time. The effect of H/RZ on tuberculosis diminished over time (P = 0.011) but the cumulative risk of tuberculosis in the first 2.5 years was significantly lower in the H/RZ group than the placebo group (rate ratio 0.55; 95% confidence interval 0.32-0.93; P = 0.028). There was no significant effect of PT on mortality or progression markers. Tuberculosis was associated with an increased mortality (adjusted rate ratio 1.96; 95% confidence interval 1.21-3.18; P = 0.006). CONCLUSIONS: Both PT regimens protect against tuberculosis for at least 2.5 years but appear to have no effect on HIV progression or mortality. These results may be used in cost-effectiveness models of PT.

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Drug-resistant tuberculosis in Africa.

Africa has the highest incidence rate per capita of tuberculosis, although the rate varies among the African countries from 17.8% in Cameroon to 70% in Botswana, Zambia, and Zimbabwe. Nevertheless, the levels of drug resistance are relatively low, compared to countries like Russia and Estonia. Because treatment of MDR TB is beyond the reach of most African countries, prevention of the development of resistance should be a major priority. Establishment of programs to ensure prompt diagnosis of TB and adequate treatment with supervision should be undertaken by national governments with cooperating partners.

The effects of BCG immunization and human immunodeficiency virus infection on dual skin test reactions to purified protein derivative and Mycobacterium avium sensitin among adults in Zambia.

SETTING: University hospital in Lusaka, Zambia. OBJECTIVE: To determine the effects of childhood bacille Calmette-Guerin (BCG) immunization and human immunodeficiency virus (HIV) infection on dual skin test reactions to purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) in a developing country. DESIGN: Descriptive cross-sectional study. RESULTS: Dual skin testing was performed on 112 adults, 58 HIV-positive and 54 HIV-negative. Forty-seven (42%) of 112 had PPD reactions > or =10 mm and 52 (46%) had MAS reactions > or =10 mm. PPD reactions > or =10 mm were present in 30 (63%) of 48 BCG-positive subjects compared to 17 (27%) of 64 BCG-negative subjects (P<0.001). Nineteen (33%) of 58 PPD or MAS skin test positive subjects were PPD dominant, 15 (26%) were MAS dominant, and 24 (41%) were non-dominant. MAS dominant and non-dominant reactions were significantly reduced in HIV-positive subjects, and non-dominant reactions were increased in BCG-positive subjects. CONCLUSIONS: Childhood BCG immunization is associated with PPD reactions > or =10 mm among adults. Reduced PPD reaction rates in HIV-positive adults appear to be due to a loss of BCG-induced PPD reactivity. Prior infection with M. avium complex is detectable in a significant proportion of adults in a developing country.

Effect of Mycobacterium vaccae (SRL172) immunotherapy on radiographic healing in tuberculosis.

OBJECTIVE: Controlled trials have failed to show an effect of Mycobacterium vaccae immunotherapy on treatment outcome and mortality in patients with tuberculosis (TB); however, several studies have suggested improvement in radiographic clearing and resolution of cavitary disease. METHODS: To assess the effect of M. vaccae immunotherapy on radiographic healing in pulmonary TB, chest X-rays from three randomized placebo-controlled trials of M. vaccae given as a single injection during the first 2 weeks of treatment were interpreted by a single, masked assessor using a standard scheme. Endpoints were the overall degree of radiographic improvement or deterioration and changes in cavitary disease at the end of antituberculosis treatment and follow-up. RESULTS: Of 1018 patients (478 HIV-infected; 540 HIV-uninfected) with an end of treatment or end of follow-up X-ray analyzed, 496 received M. vaccae and 522 received placebo. There was no difference in radiographic improvement or deterioration or cavitary disease at the end of treatment or follow-up comparing the M. vaccae and placebo groups. Results were similar comparing HIV-infected and HIV-uninfected patients. CONCLUSION: Adjunctive immunotherapy of drug-susceptible pulmonary TB with M. vaccae during the first 2 weeks of treatment did not improve radiographic responses to treatment or resolution of cavitary disease.

Recruitment to a trial of tuberculosis preventive therapy from a voluntary HIV testing centre in Lusaka: relevance to implementation.

To determine the number of clients attending for voluntary human immunodeficiency virus (HIV) testing who are able to enter a trial of preventive therapy for tuberculosis, and the factors that determine who receives therapy, we studied 475 consecutive people attending for an HIV test at Lusaka's first voluntary HIV testing centre and the preventive therapy study clinic at the University Teaching Hospital, Lusaka, Zambia. Semi-structured interviews were conducted by counsellors and collated with recruitment data from the trial. Two hundred and twenty-five people were seropositive, of whom 201 returned to collect their results; 77 (38%) of these (16% of the total number screened) entered the trial. Reasons for not entering the trial included exclusion by trial protocol (30), including 18 who had active tuberculosis; psychological adjustment to a positive result (27); death (6); worries about confidentiality (3); the experimental nature of the trial (12); attitudes of staff in the hospital (5); and cost of transport (7). Targeting preventive therapy at those who are already choosing to be tested for HIV seems appropriate and may be cost-effective. Although visiting a hospital may deter some people, the prevalence of active tuberculosis among this group emphasized the importance of arranging adequate screening facilities.

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

PIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection. Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989. Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA. A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment. The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48%. The median survival of HIV-positive patients was 22 months. The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001). Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01). At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality. Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients¿ (rate ratio 0.24, p = 0.02). 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive. 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis. Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis.

Prospects for new tuberculosis treatment in Africa.

Health services in Africa are being overburdened by a continuous increase of cases of tuberculosis (TB), largely resulting from the large pool of infected individuals becoming co-infected with HIV. To help deal with the situation, TB treatment schedules need to be shorter and simpler, with minimal contact between the patient and the service provider required, if the problems of non-compliance and of ineffective service provision are to be overcome. Various drugs not marketed for use in the treatment of TB are currently under investigation for their potential roles in the simplification or shortening of treatment schedules. These mainly include the long-acting rifamycins and the fluoroquinolones. Furthermore, new drug development is focused on an understanding of the host-pathogen interaction leading to infection, latency and disease. Of these, latency is least understood. The use of molecular diversity and combinatorial chemistry, proteomics, and the use of the whole genome to discover drug targets are expected to produce new lead compounds for turning into drugs to treat active, latent and multi-drug-resistant TB more effectively in the foreseeable future.

Radiological features of pulmonary tuberculosis in 963 HIV-infected adults at three Central African Hospitals.

Tuberculosis is one of the most important infectious complications in human immunodeficiency virus (HIV)-infected individuals in sub-Saharan Africa. In this radiological study, we detail the chest radiographic findings of Zairean and Zambian adults with a diagnosis of AIDS and tuberculosis as seen at three Central African Hospitals. Between 1992 and 1995, consecutive chest radiographs of 963 HIV-infected adults aged between 16 years and 56 years with microbiologically confirmed tuberculosis (TB) were reviewed: (1) 362 adults from Sendwe General Hospital, Lubumbashi, Zaire, (2) 175 from Mama Yemo Hospital, Kinshasa, Zaire, and (3) 426 adults from The University Teaching Hospital (UTH), Lusaka, Zambia. During the same period consecutive chest radiographs from 1000 age-matched HIV-negative adults with tuberculosis were collected for comparative purposes. Comparison of the two groups showed that the HIV-infected group of patients with tuberculosis had a significantly higher proportion of lymphadenopathy (26% vs 13%; P = 0.001), pleural effusions (16% vs 6.8%; P = 0.001), miliary shadowing (9.8% vs 5%; P = 0.001), an interstitial pattern (12% vs 7%; P = 0.01) and consolidation (10% vs 3%; P = 0.001). There was significantly less cavitation (33% vs 78%; P = 0.001) and atelectasis (12% vs 24%; P = 0.001) seen in the HIV-positive group compared to the HIV-negative group of patients. These patterns of radiographic changes were consistently seen across all three hospital sites. The radiographic appearances in HIV-infected individuals with TB is discussed.

The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate. They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia. 174 (73%) tested positive for HIV. HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs. 17% and 12%, respectively; p 0.001). They were less likely to have positive sputum tests than HIV-negative patients (36% vs. 57% for smear; p = 0.005 and 39% vs. 55% for culture; p = 0.03). HIV-positive patients were more likely to receive standard TB therapy (62% vs. 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs. 37%; p = 0.001). HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs. 9%). Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients. They also had similar laboratory and radiological findings. HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs. 4%; hazard ratio = 5.1; p = 0.03). One HIV-positive patient with a rash died. Thiacetazone was responsible for the rashes. Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs. 6/100 person years; rate ratio = 4; p = 0.03). Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment. High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment.

Neopterin, beta 2-microglobulin, and acute phase proteins in HIV-1-seropositive and -seronegative Zambian patients with tuberculosis.

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period.

Safety and immunogenicity of a five-dose series of inactivated Mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis.

Five doses of inactivated Mycobacterium vaccae vaccine were administered intradermally to 22 human immunodeficiency virus (HIV)-infected patients (11 bacille Calmette-Guérin [BCG]-positive and 11 BCG-negative) in Zambia whose CD4 lymphocyte counts were >/=200 cells/mm(3). HIV viral load and lymphocyte proliferation responses were compared for vaccine recipients and 22 HIV-infected control patients (11 BCG-positive and 11 BCG-negative). Immunization was safe and well tolerated in all patients, and induration at the vaccine site decreased from dose 1 to dose 5. A transient decrease in HIV viral load was observed in BCG-positive vaccine recipients after dose 3 but not after subsequent doses. Median lymphocyte stimulation indices to M. vaccae were 6.0 in vaccine recipients and 2.3 in control patients (P<.001). Stimulation indices were >/=3.0 in 19 vaccine recipients (86%) and 7 control patients (32%; P=.001). A 5-dose series of vaccination with inactivated M. vaccae is safe in HIV-infected patients and induces lymphocyte proliferation responses to the vaccine antigen. M. vaccae vaccine is a candidate for the prevention of tuberculosis in HIV infection.