Unusual sex differences in tuberculosis notifications across Pakistan and the role of environmental factors.

In developing countries, only one-third of new tuberculosis cases notified are from women. It is not clear whether tuberculosis incidence is lower in women than men, or whether notification figures reflect under-detection of tuberculosis in women. Pakistan, however, presents an unusual pattern of sex differences in tuberculosis notifications. While 2 of the 4 provinces (Sindh and Punjab) report more notifications from men (female to male ratios 0.81 and 0.89 respectively in 2009), the other 2 provinces (Khyber-Pakhtunkhwa and Balochistan) consistently report higher numbers of smear-positive tuberculosis notifications from women than men (1.37 and 1.40). No other country is known to have such a large variation in the sex ratios of notifications across regions. Large variations in female to male smear-positive notification ratios in different settings across a single country may indicate that environmental factors, rather than endogenous biological factors, are important in influencing the observed sex differences in tuberculosis notifications.

Smoking and HIV associated with subclinical tuberculosis: analysis of a population-based prevalence survey.

BACKGROUND: Despite multiple tuberculosis (TB) prevalence surveys reporting a relatively high frequency of bacteriologically confirmed, active TB among individuals reporting no typical symptoms of disease, our understanding of this phenomenon is limited.OBJECTIVE: To quantify the epidemiological burden and estimate associations between individual-level variables and this "subclinical" presentation.METHODS: We performed a secondary analysis of TB prevalence survey data from the South African communities of the Zambia, South Africa Tuberculosis and AIDS Reduction trial. Generalized estimating equations were used to estimate the association between individual-level demographic, behavioral, socio-economic, and medical variables and the risk of bacteriologically positive TB among participants not reporting any symptoms consistent with active TB.RESULTS: The crude prevalence of TB was 2222.1 cases per 100 000 population (95% CI 2053.4-2388.5); 44.7% (295/660) of all documented prevalent cases of TB were subclinical. Current tobacco smoking (OR 2.37, 95% CI 1.41-3.99) and HIV-positive status (OR 3.26, 95% CI 2.31-4.61) were significantly associated with subclinical TB.CONCLUSION: Individuals who smoke or have HIV may be at increased risk of active TB and not report typical symptoms consistent with disease. This suggests possible shortcomings of symptom-based case finding which may need to be addressed in similar settings.

High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies.

BACKGROUND: There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or =12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. METHODS: The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004-2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. RESULTS: There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151-2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 56-75 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17-34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89-433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10-18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6-34). CONCLUSIONS: This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guérin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic.

Disseminated bacille Calmette-Guérin disease in HIV-infected South African infants.

OBJECTIVE: To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged

Comparison of four culture systems for Mycobacterium tuberculosis in the Zambian National Reference Laboratory.

SETTING: National TB Reference Laboratory, Zambia. OBJECTIVE: To compare four TB culture systems when used in a resource-limited setting. DESIGN: Comparison of four culture systems: automated Mycobacterium Growth Indicator Tube (AMGIT) 960, manual MGIT (MMGIT) and two Löwenstein-Jensen (LJ) culture media-commercial (CLJ) and homemade (HLJ). RESULTS: A total of 1916 sputum specimens were received, of which 261 (13.6%) were positive on microscopy. Mycobacterium tuberculosis complex (MTC) was isolated on at least one of the media in 410 (21.4%) specimens: MMGIT recovered 336 (17.5%) MTC, AMGIT 329 (17.2%), CLJ 192 (10.0%) and HLJ 184 (9.6%). The median time to detection for smear-negative specimens was 14 days for AMGIT, 16 days for MMGIT and 34 days for both LJ. Isolation of non-tuberculous mycobacteria (NTM) was more frequent in both MGIT systems (3.5%) than in CLJ (0.9%) and HLJ (0.8%). Contamination rates were high: 29.6% on AMGIT, 23.8% on MMGIT, 14.9% on CLJ and 12.5% on HLJ. CONCLUSION: Despite high contamination rates, either MGIT system considerably improved both the yield and the time to detection of MTC compared to LJ media. Investments in infrastructure and training are needed if culture is to be scaled up in low-income settings such as this.

A multidisciplinary method to map potential tuberculosis transmission 'hot spots' in high-burden communities.

BACKGROUND: Global control of the tuberculosis (TB) epidemic remains poor, especially in high-burden settings where ongoing transmission sustains the epidemic. In such settings, a significant amount of transmission takes place outside the household, and practical approaches to understanding transmission at community level are needed. OBJECTIVE: To identify and map potential TB transmission 'hot spots' across high-burden communities. SETTING AND DESIGN: Our method draws on data that qualitatively describe a high-burden community in Cape Town, South Africa. Established transmission principles are applied to grade the potential TB transmission risk posed by congregate settings in the community. Geographic information systems (GIS) technology then creates a visual map, locating potential transmission 'hot spots' in the community. RESULTS: Drinking places (shebeens), clinics and churches (often gatherings in confined homes) emerge as gathering places that potentially pose a high transmission risk, particularly if located in overcrowded and impoverished areas of the community. CONCLUSION: This proof-of-concept study demonstrates that combining qualitative techniques with GIS mapping may improve our understanding of potential TB transmission within a community and guide public health interventions to enhance TB control efforts.

Cost of tuberculosis diagnosis and treatment from the patient perspective in Lusaka, Zambia.

SETTING: Urban primary health centres in Lusaka, Zambia. OBJECTIVES: 1) To estimate patient costs for tuberculosis (TB) diagnosis and treatment and 2) to identify determinants of patient costs. METHODS: A cross-sectional survey of 103 adult TB patients who had been on treatment for 1-3 months was conducted using a standardised questionnaire. Direct and indirect costs were estimated, converted into US$ and categorised into two time periods: 'pre-diagnosis/care-seeking' and 'post-diagnosis/treatment'. Determinants of patient costs were analysed using multiple linear regression. RESULTS: The median total patient costs for diagnosis and 2 months of treatment was $24.78 (interquartile range 13.56-40.30) per patient--equivalent to 47.8% of patients' median monthly income. Sex, patient delays in seeking care and method of treatment supervision were significant predictors of total patient costs. The total direct costs as a proportion of income were higher for women than men (P < 0.001). Treatment costs incurred by patients on the clinic-based directly observed treatment strategy were more than three times greater than those incurred by patients on the self-administered treatment strategy (P < 0.001). CONCLUSION: Clinic-based treatment supervision posed a significant economic burden on patients. The creation or strengthening of community-based treatment supervision programmes would have the greatest potential impact on reducing patients' TB-related costs.

Costs and cost-effectiveness of tuberculosis cultures using solid and liquid media in a developing country.

SETTING: The expansion of culture has been proposed to aid tuberculosis (TB) control in developing countries. OBJECTIVES: To examine the cost and cost-effectiveness at the Zambian National TB Reference Laboratory of homemade and commercially produced Löwenstein-Jensen culture (HLJ and CLJ) as well as automated and manually read liquid culture (AMGIT and MMGIT). DESIGN: Costs were estimated from the provider's perspective and based on the average monthly throughput. Cost-effectiveness estimates were based on yield during the study period. RESULTS: All techniques show comparable costs per culture (between US$28 and $32). Costs per Mycobacterium tuberculosis specimen detected were respectively US$197, $202, $312 and $340 for MMGIT, AMGIT, CLJ and HLJ. When modelled for the maximum throughput, costs were above US$95 per M. tuberculosis specimen detected for all techniques. When only performed among smear-negative specimens, costs per additionally identified M. tuberculosis would be US$487 for MMGIT and higher for other methods. CONCLUSION: Based on cost-effectiveness grounds, liquid media compare well with conventional solid media, especially where yield of MGIT is substantially higher than that of LJ media. The results indicate high overall costs per culture; the expansion of culture to decentralised levels with lower throughputs may result in even higher costs.

Secondary analysis of tuberculosis stigma data from a cluster randomised trial in Zambia and South Africa (ZAMSTAR).

SETTING: Zambian and South African TB and HIV Reduction (ZAMSTAR) cluster-randomised trial (CRT) communities, 2006-2009. OBJECTIVES: To develop TB stigma items, and evaluate changes in them in response to a household intervention aimed at reducing TB transmission and prevalence but not tailored to reduce stigma. DESIGN: TB stigma was measured at baseline and 18 months later among 1826 recently diagnosed TB patients and 1235 adult members of their households across 24 communities; 12 of 24 communities were randomised to receive the household intervention. We estimated the impact of the household intervention on TB stigma using standard CRT analytical methods. RESULTS: Among household members, prevalence of blame and belief in transmission myths fell in both study arms over time: adjusted prevalence ratios (aPRs) comparing the household intervention with the non-household intervention arm were respectively 0.61 (95%CI 0.26-1.44) and 0.77 (95%CI 0.48-1.25) at 18-month follow-up. Among TB patients, at baseline a low percentage experienced social exclusion and poor treatment by health staff and a relatively high percentage reported 'being made fun of', with little change over time. Disclosure of TB status increased over time in both study arms. Internalised stigma was less prevalent in the household arm at both baseline and follow-up, with an aPR of 0.85 (95%CI 0.41-1.76). Variability in stigma levels between countries and across communities was large. CONCLUSION: Robust TB stigma items were developed. TB stigma was not significantly reduced by the household intervention, although confidence intervals for estimated intervention effects were wide. We suggest that stigma-specific interventions are required to effectively address TB stigma.

Health care workers' gender bias in testing could contribute to missed tuberculosis among women in South Africa.

SETTING: Eight communities with high tuberculosis (TB) prevalence, Western Cape, South Africa. OBJECTIVE: To identify sex differences in TB health-seeking behaviour and diagnosis in primary health care facilities and how this influences TB diagnosis. DESIGN: We used data from a prevalence survey among 30,017 adults conducted in 2010 as part of the Zambia, South Africa Tuberculosis and AIDS Reduction (ZAMSTAR) trial. RESULTS: A total of 1670 (5.4%) adults indicated they had a cough of ⩾2 weeks, 950 (56.9%) of whom were women. Women were less likely to report a cough of ⩾2 weeks (5.1% vs. 6.4%, P < 0.001), but were more likely to seek care for their cough (32.6% vs. 26.9%, P = 0.012). Of all adults who sought care, 403 (80.0%) sought care for their cough at a primary health care (PHC) facility (79.0% women vs. 81.4% men, P = 0.511). Women were less likely to be asked for a sputum sample at the PHC facility (63.3% vs. 77.2%, P = 0.003) and less likely to have a positive sputum result (12.6% vs. 20.7%, P = 0.023). CONCLUSION: The attainment of sex equity in the provision of TB health services requires adherence to testing protocols. Everyone, irrespective of sex, who seeks care for a cough of ⩾2 weeks should be tested.

Coverage of clinic-based TB screening in South Africa may be low in key risk groups.

The South African Ministry of Health has proposed screening all clinic attendees for tuberculosis (TB). Amongst other factors, male sex and bar attendance are associated with higher TB risk. We show that 45% of adults surveyed in Western Cape attended a clinic within 6 months, and therefore potentially a relatively high proportion of the population could be reached through clinic-based screening. However, fewer than 20% of all men aged 18-25 years, or men aged 26-45 who attend bars, attended a clinic. The population-level impact of clinic-based screening may be reduced by low coverage among key risk groups.

Le Ministère de la Santé d'Afrique du Sud a proposé de dépister la tuberculose (TB) chez tous les patients visitant un centre de santé. Parmi d'autres facteurs, le sexe masculin et la fréquentation des bars sont associés à un risque plus élevé de TB. Nous montrons que 45% des adultes dépistés dans la province du Cap Ouest s'étaient rendus dans un centre de santé au cours des 6 derniers mois et c'est pourquoi une proportion relativement élevée de la population pourrait être atteinte à travers un dépistage en centre de santé. Cependant, moins de 20% de tous les hommes âgés de 18­25 ans, ou des hommes âgés de 26­45 ans qui fréquentent les bars, se rendent dans un centre de santé. L'impact sur la population de ce type de dépistage pourrait donc être réduit par une faible couverture parmi les groupes à risque majeur.

El Ministerio de Salud de Suráfrica propuso una detección sistemática de la tuberculosis (TB) a todas las personas que acudían a los consultorios. Entre los factores asociados con un mayor riesgo de padecer TB están el sexo masculino y la frecuentación de bares. El presente artículo pone de manifiesto que 45% de los adultos encuestados en la Ciudad del Cabo había acudido a un establecimiento de salud en los últimos 6 meses, por lo cual se pudo llegar a una proporción relativamente alta de la población mediante esta detección sistemática. Sin embargo, menos del 20% de todos los hombres entre los 18 y los 25 años, o entre los 26 y los 45 años de edad que frecuenta los bares, acudió a los establecimientos de salud. La repercusión a escala de la población de una detección sistemática realizada en los consultorios podría verse atenuada por una baja cobertura de los grupos más vulnerables.

'Kuyendela odwala TB'--visiting TB patients: the widening role of home-based care organisations in the management of tuberculosis patients in Lusaka, Zambia.

OBJECTIVE: To explore the widening role of home-based care (HBC) organisations in the management of TB patients in Lusaka, Zambia, in 1999. DESIGN: In a purposeful sample of eight HBC organisations and 1 hospice in Lusaka, 142 TB patients under HBC, 54 care givers, 42 TB patients not under HBC and 9 managers were interviewed. RESULTS: At least 50% of TB patients in Lusaka are cared for by HBC. The role of HBC in management of TB patients included food aid, practical and emotional support through the visits of voluntary care givers and, often, medical advice and treatment. TB diagnosis is carried out within the government health facilities. Five HBC organisations supplied anti-tuberculosis drugs, and three tried to carry out direct observation of treatment. The majority of the TB patients said their situation improved under HBC. Management was undermined by poor record keeping, sporadic anti-tuberculosis drug supplies, stigmatising preventive messages, limited supervision of care givers and poor coordination with the District Health Services. CONCLUSION: HBC organisations have become a key partner in TB control, looking after half the TB patients in Lusaka from diagnosis onwards, and complementing the public system. However, the quality of their management of TB and their partnership with government need to improve.

Modelling the economic benefits of tuberculosis preventive therapy for people with HIV: the example of Zambia.

OBJECTIVE: To assess the economic benefits and costs of providing isoniazid preventive therapy for tuberculosis (TB) in HIV-infected persons in Zambia. DESIGN: A spreadsheet model incorporating variables drawn from published studies and unpublished data. SUBJECTS: Data drawn from a number of different studies and published literature involving a range of subjects. SETTING: Zambia. RESULTS: Using data primarily from Zambia we have modelled the costs and benefits of a TB preventive therapy programme using daily isoniazid for 6 months. The basecase scenario assumes recruitment at a voluntary testing and counselling site where HIV seroprevalence is 30%; persons with HIV have a 25% probability of developing active TB during their lifetime; two additional cases of TB would be prevented per person completing a course of preventive therapy; compliance would be 63%, and the efficacy of the isoniazid in preventing active TB of 60%. The costs under this scenario would exceed the benefits by a factor of 1.16 [benefit: cost ratio (BCR) of 0.86]. However, if preventing one case of TB prevented an additional five cases, the benefits would exceed the costs by a significant margin (BCR of 1.71). Other scenarios indicate that the targeted preventive therapy of persons with HIV whose occupation or living situation places them in contact with a large number of others (teachers and students, health personnel, military and police, miners, prisoners, etc.) would yield significant net benefit. The operational challenge for TB preventive therapy is thus to identify and target large numbers of such persons.

PIP: The authors used available data from selected published literature to assess the economic costs and benefits of providing daily isoniazid preventive therapy for tuberculosis (TB) for 6 months in HIV-infected persons in Zambia. The base case scenario assumes recruitment at a voluntary testing and counseling site where HIV seroprevalence is 30%, HIV-infected individuals have a 25% probability of developing active TB during their lifetime, two additional cases of TB would be prevented per person completing a course of preventive therapy, compliance would be 63%, and an efficacy of isoniazid in preventing active TB of 60%. The costs under that scenario would exceed benefits by a factor of 1.16, or a benefit/cost ratio (BCR) of 0.86. However, if preventing one case of TB prevented an additional five cases, the benefits would exceed the costs by a BCR of 1.71. Other scenarios indicate likely significant net benefits from the targeted preventive therapy of HIV-infected persons whose occupation or living situation brings them into contact with a large number of other people.

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.

Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex workers in Nairobi, Kenya.

OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV-related tuberculosis in a female cohort, and to investigate the relative importance of recently transmitted infection and reactivation in the pathogenesis of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of female sex workers in Nairobi were enrolled in a prospective study. Women were followed up regularly and seen on demand when sick. METHODS: Between October 1989 and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women. Standard protocols were used to investigate common presentations. Cases of tuberculosis were identified clinically or by culture. All available Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS: Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV-infected women; no disease was seen in seronegative sex workers (P = 0.0003). The overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV-infected participants. In purified protein derivative (PPD) skin test-positive women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years in PPD-negative women. Twenty incident cases (41%) were clinically compatible with primary disease. DNA fingerprint analysis of strains from 32 incident cases identified two clusters comprising two and nine patients; allowing for index cases, 10 patients (28%) may have had recently transmitted disease. Three out of 10 (30%) patients who were initially PPD skin test-negative became PPD-positive. Taken together, 26 incident cases (53%) may have been recently infected. DNA fingerprint analysis also identified two (50%) of the four recurrent tuberculosis episodes as reinfection. CONCLUSIONS: Substantial recent transmission of tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers. It may be incorrect to assume in other regions of high tuberculosis transmission that active HIV-related tuberculosis usually represents reactivation of latent infection.

PIP: A 3-year (1989-92) prospective study of 587 HIV-positive and 132 HIV-negative commercial sex workers in Nairobi, Kenya, revealed substantial recent transmission of tuberculosis in the HIV-infected group. The cohort was enrolled at a community clinic that provides counseling, sexually transmitted disease services, and free condoms. In HIV-positive women, 49 incident and 4 recurrent episodes of tuberculosis were diagnosed during the study period; there were no tuberculosis cases among HIV-negative women. The overall incidence rate of tuberculosis was 34.5/1000 person-years among HIV-positive women. 20 incident cases (41%) met the clinical case definition of primary disease. DNA fingerprint analysis of strains from 32 incident cases suggested 10 women (28%) may have had recently transmitted disease. 3 of 10 women who were initially purified protein derivative (PPD) skin test-negative became PPD-positive. Clinical presentation, tuberculin skin testing, and strain clustering data all independently suggested that substantial Mycobacterium tuberculosis transmission was occurring in HIV-infected prostitutes during the study period. As many as 26 (53%) of the 49 patients with incident disease may have recently acquired tuberculosis and DNA fingerprint analysis identified 2 (50%) of the 4 recurrent tuberculosis episodes as reinfection. These findings challenge the assumption that tuberculosis in HIV-infected individuals represents reactivation of latent endogenous infection.

Non-Hodgkin's lymphoma associated with the acquired immune deficiency syndrome: a report of five cases.

We report a series of five HIV positive patients with histologically proven non-Hodgkin's lymphoma. The paper illustrates the difficulties experienced in both the clinical diagnosis and its histological confirmation. In this series we have confirmed the predominance of aggressive histological variants and the high frequency of extra-nodal involvement. The prognosis despite treatment was poor; only one patient entered complete remission and the mean survival was only 4.3 months.

Barriers to tuberculosis control in urban Zambia: the economic impact and burden on patients prior to diagnosis.

SETTING: Chest Clinic, University Teaching Hospital, Zambia. OBJECTIVE: To study the pre-diagnosis economic impact, burden, and barriers to care-seeking for tuberculosis patients in urban Zambia. DESIGN: In-depth interviews conducted over a 9-week period with adult in-patients and out-patients registering with new pulmonary tuberculosis; data analysis using Epi Info. RESULTS: Interviews were completed by 202 patients: 64% normally worked, but 31% stopped due to their tuberculosis, with an average of 48 days off. The mean duration of illness prior to their tuberculosis registration was 63 days, with 64% of patients delaying in presenting to the Chest Clinic. Of these, 38% blamed money shortages for their delay. In seeking diagnosis, patients incurred a mean total cost equivalent to 127% of their mean monthly income (pounds sterling UK 40 [$US 59]); direct expenditures represented 60% of this cost. In addition, patients lost, on average, 18 work days prior to diagnosis. Care-givers incurred costs equivalent to 31% of the mean monthly income (pounds sterling UK 10 [$US 15]). CONCLUSION: The economic burden of tuberculosis on patients creates barriers to prompt diagnosis which may lead to continuing transmission of the infection. Important economic barriers include transportation expenditure, cost of 'special food', and lost income. These barriers may be reduced through interventions that reduce the number of health encounters, travel distances and duration of illness before diagnosis.