University of Zambia Medical Library
HIV/AIDS and Tuberculosis (AIDS in Zambia Bibliography #85-100)
- (#85) "Prevalence of HIV infection among patients with leprosy and tuberculosis in rural Zambia"
Meeran, K. (1989) British Medical Journal, 298, pp 364-365
Geographical area: Chikankata, Southern Province; Key words: TB, Leprosy, mycobacteria; Location: UNZA Medical Library
Mycobacterial infections have been associated with HIV infection. Much evidence exists
of tuberculosis as a presenting feature of HIV infection or AIDS-related complex. High
grade pathogens such as Mycobacterium tuberculosis develop early whereas low grade
pathogens such as Mycobacterium avium-intracellulare emerge only when immune
deficiency is more advanced. There are few reports of a direct association between HIV
infection and leprosy, though clinical leprosy has long been associated with a defect in
cell mediated immunity. I studied patients in Zambia to see whether an association
between leprosy and HIV infection existed similar to that shown for tuberculosis.
Subjects, methods, and results: The study comprised subjects presenting to Chikankata
Salvation Army Hospital from October to December 1987. This is a busy, 240 bed rural
hospital in the Southern province of Zambia. Patients presenting with leprosy and
tuberculosis and blood donors and surgical patients were included. A full history was
taken from patients about the onset of symptoms and progression of disease. Personal
details such as age, sex, and area of residence were also recorded.
Venous blood samples were allowed to clot and the serum separated by centrifugation.
Antibodies to HIV were detected with the Wellcozyme VK5 1 competitive enzyme
linked immunosorbant assay (ELISA). Non-repeatable false positive results are known
to occur with competitive ELISAs, so all tests that did not give an obvious negative
result were repeated on another sample of blood taken from the patient at least one week
later. Thus all positive results were confirmed. In addition, many samples were retested
with both the Fujirebio HIV agglutination assay (in which agglutination indicated a
positive result) and Elavia (a non-competitive ELISA) kit.
No patients from urban areas had leprosy. Of 18 new patients with leprosy, six (33 per
cent) were positive for HIV antibody. Of 54 patients with suspected tuberculosis, 27 (50
per cent) were positive for HIV antibody. 18 of the 54 had active pulmonary
tuberculosis, with results of smears of sputum positive for acid fast bacilli, and eight of
these (44 per cent) were also positive for HIV antibody. By comparison, only seven out
of 63 blood donors (11 per cent) and two out of 42 surgical patients (5 per cent) were
positive for HIV antibody.
The prevalence of HIV infection was significantly higher among patients with leprosy
than among blood donors (p<0.05) or surgical patients (p<0.01). Some patients came
from Lusaka, which may have a higher prevalence of HIV infection than rural Zambia.
When the analysis was restricted to rural residents, patients with leprosy still had a
higher prevalence of HIV infection than surgical patients or blood donors (p<0.001).
Comment: The present study may have been subject to serious limitations in the
selection of cases and controls. In particular, patients with leprosy and tuberculosis who
presented to hospital were probably not typical of all patients with these diseases. The
patients with leprosy tended to have serious symptoms, such as paralysis or neuritis,
rather than a single skin lesion. Thus the results may indicate an increased number of
self referrals to hospital among patients with HIV infection. Because of the small
number of patients sampling error cannot be discounted. In addition, the controls were
not matched to the cases at the time of the study, though some attempt was made to take
this into account in the analysis. Nevertheless, the study suggests that as with
tuberculosis there may be an association between leprosy and HIV infection which
would have serious implications for programmes to control leprosy. Further
epidemiological studies should be conducted to confirm this association and to monitor
any change in the epidemiological characteristics of leprosy. -
- (#86) Impact of HIV on Tuberculosis in Zambia: A Cross-Sectional Study
Elliot. A.M., Luo, N., Tembo, G., Halwiindi, B., Steenbergen, G., et al.
(1990) British Medical Journal Vol. 301(6749); 1990; pp 412-5
Geographical area: Lusaka;
Key words: TB;
Location: UNZA Medical Library
Objective: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa.
Design: Cross-sectional study.
Setting: Outpatient clinic in a teaching hospital, Lusaka, Zambia.
Patients: 346 Adult patients with tuberculosis.
Results:
Overall, 206 patients (95 per cent confidence internal 54 per cent to 65 percent) were positive for HIV in one or both assays used. The peaks for both tuberculosis
and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of
patients with confirmed pulmonary tuberculosis, 73/149 (49 per cent; to 57 per cent)
were positive for HIV; 67/83 (81 per cent; 70 per cent to 89 per cent), patients with
pleural disease and 16/19 (84 per cent; 60 per cent to 97 per cent), patients with
pericardial disease were positive. HIV-positive patients with positive sputum culture
were less likely to have had a positive sputum smear, and their chest x-ray films less
often showed classic upper zone diseases or cavitation. Of 72 patents who fulfilled
clinical criteria for AIDS, 17 were negative for HIV.
Conclusions: The high prevalence of HIV in patients with tuberculosis suggests that
an epidemic of reactivating tuberculosis is arising in those who are infected with HIV.
-
- (#87) The impact of human immunodeficiency virus on tuberculosis in Zambia: Infectivity
Pobee, J., Nunn, P., Hayes, R., McAdam, K., (1991) Paper presented at the
VIIth International Conference on AIDS, Florence, 1991.
Geographical area: Lusaka;
Key words: TB, BCG;
Location: unknown
Objectives: To compare the infectivity of HIV-positive and HIV-negative patients to their household contacts.
Methods:
353 contacts, both adults and children, of tuberculosis patients with positive sputum smear, and or culture were examined by Mantoux test (2TU). Those who consented (180 individuals) were also examined for HIV antibody. Thirty-nine
were excluded because the Mantoux was not read.
Results:
17 (10 per cent) contacts (1 aged less than 1 year; 16 aged 17 years or more) were HIV-positive.
| Index case/ HIV status | Total contacts | Total contacts with
Mantoux > 5mm | Contacts with active tuberculosis |
|---|
| HIV-Negative | 125 | 90 (72%) | 5 (4%) |
|---|
| Hiv-Positive | 187 | 100 (54%) | 9 (5%) |
|---|
The results showed a higher frequency of Mantoux positivity among contacts of HIV
negative tuberculosis patients (p =0.02). The finding was independent of age,
presence of BCG scar and HIV status of the contact.
Conclusion:
The evidence suggests that pulmonary tuberculosis is less infectious in HIV-positive patients.
-
- (#88) Preventive tuberculosis chemotherapy with isoniazide among persons affected with human immunodeficiency virus
Wadhawan, D., Hira, S., Mwansa, N., Tembo, G., Perine, P., (1991) Paper
presented to the VIIth International Conference on AIDS, Florence, 1991.
Geographical area: Lusaka;
Key words: TB, chemotherapy;
Location: unknown
Objectives:
To determine efficacy of isoniazide (INH) prophylaxis in prevention of Mycobacterium tuberculosis disease in adult Zambians infected with HIV-1.
Methods:
A randomised, single-blind, placebo controlled study was conducted at the
University Teaching Hospital (UTH), in Lusaka, Zambia. Nonpregnant adults with
Western blot confirmed HIV-1 infection and the absence of active tuberculosis were
recruited. Group 1. 352 patients received INH 300mg by mouth daily with vitamin B
complex (BCo) tablet daily for six months and subsequently BCo for 24 months. Group
2. 297 patients received BCo tablet daily for 30 months. Patients in both groups were
examined every 3 months and chest radiographs done every 6 months. Active
tuberculosis was diagnosed by radiographs, sputum culture or tissue biopsy.
Results:
Patients in both groups were comparable by age, sex and staging of HIV-disease as done by Walter Reed Classification. Group 1. 298 patients were followed for 293 patient years and 23 died during follow up. Three developed active tuberculosis.
Group 2. 246 patients were followed for 262 patient years; 27 died and another 20
developed active tuberculosis during follow up. All those who developed active
tuberculosis were in Walter Reed Stages III and IV at the time of recruitment.
Stratifying patients in WRIII and WRIV, the annualised incidence of active
tuberculosis among patients on BCo (placebo) was 16.2/patient years as compared to
1.8/pt yr among those on INH prophylaxis (p =0.001).
Conclusion:
INH prophylaxis significantly reduces the incidence of active tuberculosis. Prophylaxis did not delay the disease progression or reduce mortality.
-
- (#89) HIV Infection in Newly Diagnosed Tuberculosis Patients in Ndola, Zambia
Simooya, O.O., Maboshe, M.N., Kaoma, R.B., Chimfwembe, E.C.,
Thurairajah, A., et al. (1991) Central African Journal of Medicine
Vol.37(1);1991; pp 4-7
Geographical area: Ndola;
Keywords: Tuberculosis;
Location: UNZA Medical Library
Between June and December 1987, 131 patients newly admitted to the tuberculosis
wards of the Ndola Central Hospital, underwent a history and examination, chest
radiography, sputum examination an enzyme linked immuno sorbet assay (ELISA)
(Wellcome), for human immuno deficiency virus (HIV) antibodies. For all sera testing
positive, the ELISA was repeated on two different occasions before HIV seropositivity
was confirmed. Eighty-three patients (67 per cent) had tubercle bacilli on microscopy,
whilst 76 patients (58 per cent) were HIV-positive (7 patients had no sputum on
admission). Nine patients (7 per cent) had signs of disseminated tuberculosis while the
rest had evidence of pulmonary tuberculosis. Four patients (3 per cent) had normal
chest radiography, whereas the remainder had intrapulmonary lesions in their films. No
association was found between presence or absence of bacilli and HIV seropositivity
(P>0.05). HIV seropositive tuberculosis patients were more likely to be younger and
female when compared to HIV seronegative tuberculosis patients (P<0.05). It was
concluded that HIV infection is common in newly diagnosed tuberculosis patients and
that young and female patients are more likely to be HIV seropositive than their male
counterparts.
-
- (#90) Prevention of HIV Related Tuberculosis in Zambia
Mwinga, A. (1992) ongoing research
Geographical area: Lusaka;
Keywords: Tuberculosis, chemoprophylaxis;
Location: unknown
On-going clinical trial study which commenced in March l992. The objective of this
study is to determine whether chemoprophylaxis is effective and which of two different
drug regimens works better. The next phase of the study will be to examine the
feasibility and cost-effectiveness of different strategies for implementing
chemoprophylaxis. The aim is to recruit 900 individuals who are HIV-positive but have
not got tuberculosis and to treat them with one of these regimens; isoniazid alone for
six months, pyrazinamide and rifampicin together for three months or an inactive
placebo. Subjects will then be followed up carefully for up to three years and the
frequency with which tuberculosis develops in each group will be compared. The
choice of treatment is randomised and the drugs have been made up specially to look
identical so that there is no possibility for bias in deciding with is more effective. A
placebo is necessary to provide a valid comparison. -
- (#91) Interaction between Bovine and Human Tuberculosis in Southern Province
Cook, A. (1992) Study in progress
Geographical area: Southern Province;
Key words: Bovine TB, TB;
Location: unknown
Zambia, like other countries in the region, has seen a rising incidence of
tuberculosis in humans over the past few years. Much of the increase may
be due to the epidemic of HIV infection in the area. HIV infection increases
the likelihood of reactivating dormant infection but also increases
susceptibility to disease following recent infection. Prior to effective
tuberculosis control in cattle in developed countries, the positive correlation
between prevalence of human and bovine infection was well recognised.
Up to 6 per cent of human pulmonary tuberculosis and more than 20 per
cent of extrapulmonary cases were attributed to infections of bovine origin.
The prevalence of tuberculosis among traditionally owned cattle in Zambia
is unknown. Mycobacterium bovis has rarely been found in human cases
but extrapulmonary specimens are rarely cultured and both M.bovis and
M.tuberculosis are able to infect both cattle and humans. -
- (#92) How safe is BCG vaccination in children born to HIV-positive mothers?
Athale, U.A., Luo, C.M., Chintu, C. (1992) The Lancet, Vol 340, pp 434-435
Geographical area: Lusaka;
Key words: TB, BCG, paediatric AIDS;
Location: UNZA Medical Library
Objectives:
To determine why the clinical presentation of tuberculosis is so
different in HIV-infected children, and whether these children can develop
"BCGaemia" after vaccination, whereby the strain of BCG vaccine propagates,
disseminates, and causes infection and death.
Methods:
As far as possible, for every patient with a clinical diagnosis of
tuberculosis, we try to obtain microbiological confirmation (sputum, gastric lavage,
or biopsy examination).
Results:
At our hospital the frequency of HIV is 25 per cent in inpatients aged 6
months to 5 years. 37-50 per cent of paediatric and 60 per cent of adult patients with
tuberculosis were infected with HIV-1. In control children, 10.7 per cent had HIV-1,
87 per cent of patients with tuberculosis had been immunised. Since 91 per cent of
controls were immunised, protection by BCG is low. In 30-40 per cent of babies born
to HIV-positive mothers can be infected with HIV-1, BCG could disseminate in an
immuno-suppressed host, and it is difficult to diagnose AIDS in new born babies.
Conclusions:
- Is it advisable to immunise all babies at birth with BCG vaccine;
irrespective of their or their maternal HIV-antibody status?
- How ethical is it to
immunise all when the incidence of HIV infection is high?
- We suggest immunising
children at 1 year of age, because by then full-blown AIDS or HIV infection will be
evident and provide the basis for the exclusion from immunisation.
- (#93) The Zambia AIDS-related Tuberculosis (ZAMBART): Clinical Trial Study
Elliot, A., Pobee. J., McAdam. K. (1992) ongoing research
Geographical area: Lusaka;
Key words: TB, chemoprophylaxis;
Location: UNZA Medical Library
The Zambia AIDS-related tuberculosis (ZAMBART) is a clinical trial study This
research assessed both the association between HIV and tuberculosis in Zambia and
subsequently at the effects of HIV on presentation, management, outcome and
infectiousness. There are two main studies. The first was trying to prevent tuberculosis
in HIV-infected individuals by chemoprophylaxis. The second, was a laboratory based
study, looking at the mechanisms by which tuberculosis occurs and recurs in HIV-infected individuals using DNA fingerprinting.
The principal findings were:
- HIV and tuberculosis are closely associated. About 70 per cent of
patients with tuberculosis, seen at UTH, are also infected with HIV.
- Clinical features may be unusual, with more extrapulmonary disease,
particularly in lymph nodes, pleura and pericardia.
- Tuberculosis responds satisfactorily to treatment although many
patients die soon, presumably of other HIV-related causes.
- Thiacetazone, a cheap anti-tuberculous drug that has been widely used
in Zambia, is associated with an unacceptably high rate of skin reactions
some of which are severe and even fatal.
- Relapse of tuberculosis after treatment is more common amongst those
patients also infected with HIV.
- Patients with HIV-related pulmonary tuberculosis are probably less
infectious than those not infected with HIV.
-
- (#94) Tuberculosis: the neglected epidemic
Mouli C., Walker, L., Chondoka, S., Mwananyambe, N., (1992), Paper
presented to the VIIIth International Conference on AIDS, Amsterdam,
1992.
Geographical area: Kitwe;
Key words: TB, awareness;
Location: unknown
Problem statement:
There has been a dramatic increase in the incidence of new
cases of tuberculosis in Zambia (from 6,744 recorded new cases in 1985 to 16,863
in 1990). The overwhelming increase in TB coincides with the AIDS epidemic that
has struck Zambia. Studies have shown that 72 per cent of all new cases of TB are
HIV related. However, the poor economic situation has contributed to this too by
reducing the purchasing power of the people and weakening the Health Ministry's
ability to carry out effective TB prevention and control work.
Description of project:
Our project has employed a three pronged approach to tackle
this problem: - We produced a leaflet entitled "What everyone should know about
TB" directed at patients with TB and their relatives. This has been distributed to
hospitals all over the province and is used in defaulter prevention education.
- We
have sponsored several workshops to enable doctors, nurses and clinical officers in
our province to update their knowledge and thrash out common problems together.
- Our "AIDS and the workplace" leaflet deals with TB in some detail. Blue/white
collar workers are told that TB is a curable disease even if associated with HIV
infection.
Results:
Our 3 pronged approach has helped to; - Improve the knowledge, skills
and commitment of our health workers.
- Encourage patients to complete their
courses of treatment.
- Increase awareness and concern about TB in the community.
Conclusion: A great deal of clinical research has been carried out on the subject of
TB and AIDS. However, health, promotion work in this area is virtually non-
existent. To be meaningful, AIDS health promotion work must move beyond
promoting safer sex to respond to the community needs.
-
- (#95) The Application of DNA Fingerprinting to Study the Pathogenesis of HIV-related tuberculosis
Godfrey-Faussett, P. (1992) Ongoing clinical study
Geographical area: Lusaka;
Key words: TB;
Location: unknown
A clinical study for 500 isolates of M. Tuberculosis in Zambia aimed at defining the
amount of heterogeneity between strains from different regions. The objective is to
establish a DNA fingerprinting laboratory within the Pathology Department at UTH
and use it to address questions about the mechanisms by which tuberculosis arises
relevant to Zambia and other countries in the region. The findings reveal that the rate
of recurrence of tuberculosis after successful treatment is higher in patients who are
HIV- positive than those who are negative. The first aim is to compare the isolates from
patients with recurrent disease with those stored from their first episode. If pairs of
isolates are identical it suggests true relapse which implies a need for more effective or
longer treatment regimens. If pairs are distinct, it suggests that infection with a new
strain has occurred and appropriate control measures would be to try to separate
patients with tuberculosis, for instance by providing as much treatment as possible at
home rather than in hospitals or clinics where cross-infection could be occurring.
Isolates of M.Tuberculosis from all patients with proven tuberculosis in Lusaka in 1992
have been stored in duplicate by the staff of the Chest Diseases Laboratory. A random
batch of these have been subcultured to check that they remain viable, with only a low
contamination rate. -
- (#96) Tuberculosis and immunodeficiency in HIV-1 infected patients in Africa
Elliot, A.M., Hayes, R.J., Luo, N., Pobee, J.O.M., McAdam, K.P. (1993)
The Lancet, 342, p1053 (letter)
Geographical area: Lusaka;
Key words: TB;
Location: UNZA Medical Library
The association between pleural tuberculosis and HIV-1 infection is examined. The
findings of a study by Elliot et al (1993) in 182 HIV-1 positive patients in Zambia
suggest that patients with extra-pulmonary disease might be less immuno-suppressed
than those with pulmonary disease. The most striking differences were seen when
HIV-1 positive patients with pleural disease alone were compared with other HIV-1
positive patients, indices being consistently more favourable among those with
pleural disease. Besides, those with pleural effusions as the sole site of infection had
a slightly better survival than HIV-1 positive patients, although the difference was
not significant (Cox proportional hazards analysis, hazard ratio, allowing for age and
sex, 0.69, p = 0.13). With these observations the authors speculate that TB pleurisy
maybe a manifestation of primary tuberculous infection in patients with HIV
occurring in individuals whose immune system though sufficiently impaired to allow
disease to develop, retain sufficient CD4 cells to mount a major lymphocytic
inflammatory response. HIV associated extra-pulmonary TB might be
immunologically heterogenous and that, rather than the use of broad groupings,
further immunological analysis of patients disease at specific sites is warranted.
-
- (#97) Tuberculosis and HIV infection
Godfrey-Faussett, P., Mwinga, A., Raviglione, M., Hosp, M., Baggaley, R.,
et al. (1993) The Lancet 342, pp 1368-1369
Geographical area: Lusaka;
Key words: TB, chemoprophylaxis;
Location: UNZA Medical Library
The authors argue with Reeve's comment (Lancet Sept.11, p.676) that
"chemoprophylaxis in Africa will never be economically or practically viable". They
maintain that further study of preventive therapy is warranted due to the large number
of patients with both Mycobacterium tuberculosis infection and HIV infection and
because of the unusually high risk of TB in such patients. The cost of drugs used to
treat TB in developing countries is $55-75, whereas a year's course of prophylactic
isoniazid costs $2.75. If prophylaxis reduces the risk of TB to around 2.5 per cent
/person/year for each person given preventive therapy, the TB control programme
would save $8.80. Thus it is not economically viable not to use preventive therapy.
The savings would not be so great if the costs of testing for HIV-infected in Africa
were included. Reeve raises the possibility that poor compliance may lead to drug
resistance. However a real concern is that poor screening might allow patients with
active TB to start on preventive therapy, which might still select out resistant
organisms. Nonetheless it may still be cost-effective to exclude active disease before
initiation of preventive therapy. Although treatment for HIV-related TB is successful
recurrence of TB was 34 times greater in HIV-infected patients than in HIV sero-negative patients. Efforts must be directed towards early diagnosis and treatment of
sputum positive cases. These should be combined with studies to assess the place of
preventive therapy in Africa, with an emphasis on funding preventive therapy from
budgets for care of HIV-infected individuals.
-
- (#98) Chemoprophylaxis in the prevention of HIV-related tuberculosis in Zambia
Mwinga, A., Pobee, J., Luo, N., Porter, J., McAdam, K.P.W.J., (1993) Paper
presented to the IXth International Conference on AIDS, Berlin, 1993.
Geographical area: Lusaka;
Key words: Chemoprophylaxis, tuberculosis;
Location: unknown
Objectives:
To compare efficacy of twice weekly regimens of isoniazid, rifampicin and
pyrazinamide of placebo in the prevention of HIV-related tuberculosis.
Methods:
Consenting individuals from two clinics in Lusaka, Zambia were enrolled
in the study, commenced on one of the regimens, and followed up at regular intervals.
Results:
61 patients were enrolled in the study and the follow up period has now
reached two years. 54 per cent of the patients completed the course of treatment and
48 per cent reached two years follow up. One episode of tuberculosis occurred during
the follow up period. Major problems encountered were with determining eligibility
for enrollment into the study and follow up.
Conclusions:
Chemoprophylaxis in an area with a high rate of dual TB/HIV infection
may need to be considered in terms of a community approach in order to increase
compliance. -
- (#99) Cutaneous reactions to thiacetazone in Zambia - implications for tuberculosis treatment strategies
Kelly, P., Buve, A., Foster, S., McKenna, M., Donnelly, M., et al. (1994)
Transactions of the Royal Society of Tropical Medicine and Hygiene 88, pp
113-115
Geographical area: Monze, Southern Province;
Key words: TB;
Location: UNZA Medical Library
Tuberculosis in patients infected with human immunodeficiency virus (HIV) is a growing
threat to public health in Africa. Thiacetazone, one of the continent's most widely used
antituberculous agents, may lead to severe cutaneous reactions in the HIV infected
individual. We describe the impact of this reaction on the tuberculosis (TB) control
programme of a district hospital in Zambia in 1990, and examine the cost implications
of changing the standard treatment regime. We carried out a retrospective survey of
records of all patients beginning TB treatment in 1990, together with HIV test results and
the cost of all treatments given. From this we derived estimates of costs of different
regimes which are and could be used in TB control in Zambia. Severe reactions occurred
in 18.7 per cent of all HIV seropositive patients receiving thiacetazone, fatally so in 1.2
per cent (odds ratio 16.6). The greatest part of the cost of the current regime is that
attributable to the in-patient stay; we estimated that 29.4 per cent of patients would be
unable to receive drugs as out-patients but, even allowing for this, rifampicin-based
regimes given to outpatients where possible would not cost more than the current
strategy. We conclude that ethical and economic considerations support a change to
rifampicin-based regimes in areas of Africa where HIV seroprevalence is high.
-
- (#100) Tuberculosis and slim disease in Africa
Godfrey-Faussett, P., Mwinga, A., Hosp, M., Baggaley, R., Porter, J., et al.
(1994) British Medical Journal, 309, pp 1230-1231.
Geographical area: NA;
Key words: Tuberculosis;
Location: UNZA Medical Library
The cost-effectiveness of preventive treatment for TB in Africa continues to excite
controversy. Preventive treatment is likely to be effective in reducing the incidence of
active TB in those infected with both HIV and Mycobacterium tuberculosis. Without
data on how feasible or efficacious treatment is, it is not possible to derive cost-benefit
analyses. Simple calculations however, make it clear that giving 4 patients treatment
might be hoped to prevent 1 case of disease, which would result in a saving of drug
costs. In Zambia donors are funding the HIV testing of up to 5 per cent of the adult
population of Lusaka. If preventive treatment for TB proves efficacious it will be the
first medical intervention that can be offered to HIV seropositive persons, and the costs
of counselling and tests will be met for reasons other than to provide preventive
treatment. Early diagnosis and better management of TB will eventually reduce the
burden of TB infection in the community but cannot be expected to make much
immediate impact on the incidence of and associated mortality from slim disease. To
define the efficacy and to find innovative ways of delivering preventive treatment and
monitoring its cost and impact should be among the priorities of nations where the
distribution of HIV infection and TB overlap.
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