There was no significant difference in the demographic characteristics (age, gender, ethnicity, monthly income and nutritional status) between the 13 patients with tuberculosis and HTLV-1 infection and 25 patients with only tuberculosis. A large proportion of case (54%) and control patients (64%) were underweight (body mass index
18.4) and the use of alcohol was also similar in both groups. The clinical manifestations, response to TST and the presence and quantification of acid-fast bacilli (AFB) in the sputum in the two groups are shown on Table
. The presence of fever, asthenia, anorexia and weight loss were similar in the two groups (p
0.05). In both groups the frequency of hospitalization for tuberculosis, previous tuberculosis and treatment abandonment for tuberculosis was high. There was no difference regarding the frequency of responders to the TST as well as the size of induration. At the time of admission, two patients with HTLV-1 infection and tuberculosis had been receiving therapy for tuberculosis for 28 and 35
days, respectively; in both, the sputum test was negative. However, previous to the therapy, both were documented to have AFB in the sputum, which also grew M. tuberculosis
They were admitted because of toxicity to anti-tuberculosis drugs. No difference in the bacillary load was observed in the two groups at admission. The drug sensibility test revealed one M. tuberculosis
isolate with multidrug resistance and another with resistance to isoniazid and streptomycin among the cases. In the control group, there was one isolate with resistance to isoniazid, rifampicin and ethambutol and one with resistance to streptomycin. The findings of the chest x-rays were similar in the 2 groups. Cavitation was observed in more than 60% of the patients with or without HTLV-1 infection. Fibrosis and atelectasis occurred in about 50% of the cases and controls. Parenchymal destruction was higher (15.3%) in patients with HTLV-1 infection and tuberculosis than in patients with only tuberculosis. The radiologic findings in patients with HTLV-1 and tuberculosis were not compatible with those observed in patients with T cell impairment. The most common findings were fibrosis, atelectasis, pleural thickening and cavitation. All of them were similar in the two groups but the parenchymal destruction lesions were 3.5 fold higher in patients with HTLV-1 infection and tuberculosis than in patients only with tuberculosis.
Clinical and microbiologic characteristics of tuberculosis patients with or without HTLV-1 infection
The therapy for tuberculosis was similar in both groups. The majority of the patients received rifampicin, isoniazid and pyrazinamide. In 33.3% of the cases and in 28% of the controls, patients also received ethambutol. Alternative drugs were given to 15.4% of the cases and to 8% of controls.
shows the survival analysis of patients whose sputum test became negative after 10 and 20
days of therapy. As previously stated, two patients with HTLV-1 infection and tuberculosis were already on therapy and the sputum test was negative. On day 10, while 50% of the patients with tuberculosis and HTLV-1 still had AFB in the sputum, almost 90% of patients with tuberculosis only remained eliminating bacilli. At day 20, 36.4% of the patients with HTLV-1 infection and tuberculosis and 75% of those with tuberculosis only were smear test positive for AFB (p
0.07; Kaplan-Meier test). However, sputum test conversion occurred faster in patients with HTLV-1 infection and tuberculosis.
Figure 1 Survival analysis of sputum smear conversion for acid-fast bacilli during tuberculosis treatment. Tuberculosis patients with and without HTLV-1 infection, who remained test positive by acid-fast bacilli (AFB) smear microscopy after 10 and 20days (more ...)
The main side effects observed were hepatotoxicity and gastric intolerance (nausea, abdominal pain and vomit) observed in, respectively, 38.5% and 23.1% in the cases and in 28% and 36% in the controls (p
0.05). While death was observed in 2 (15.4%) of the patients with HTLV-1 infection and tuberculosis, none of the patients died in the group only with tuberculosis. Death occurred in one woman and one man. They both had cavitary lung disease, fibrosis, atelectasis and tissue destruction on chest x-rays. Death was due to acute respiratory insufficiency in one case and sepsis in the other.
Regarding HTLV-1 infection, the majority of the cases were HTLV-1 carriers. Four patients had overactive bladder that is considered to be an oligosymptomatic form of HAM. The proviral load was quite variable ranging from 8079 to 499742 copies/106cells.
The spontaneous and PPD induced TNF-α and INF-γ production in supernatants of PBMC are shown in Figure
. In cultures without stimulus, the median TNF-α level among the group with HTLV-1 infection and tuberculosis (368
pg/mL) ranging from 128 to 5527
pg/mL was higher (p
0.004) than that observed in patients with only tuberculosis (73
pg/mL), which ranged from 0 to 738
A). In cultures stimulated with PPD, the median and range of TNF-α level in the co-infected patients, 0
pg/mL (0 – 2295
pg/mL), was lower (p
0.01) than in patients with only tuberculosis, which was 386
pg/mL (0 – 3847
B). The production of IFN-γ in unstimulated cultures in patients with HTLV-1 infection and tuberculosis 732
pg/mL (0 – 2677
pg/mL) was higher (p
0.004) than in patients with only tuberculosis, which was 15
pg/mL (0 – 444
C). There was no difference between the groups in the production of IFN-γ in PPD stimulated cultures (Figure
D). There was no difference (p
0.05) in the production of IL-10 in both unstimulated and PPD stimulated cultures; majority of the co-infected patients (60%) and 45% of patients with tuberculosis without HTLV-1 infection had no detectable IL-10 production (data not shown). Addition of anti-IL-10 monoclonal antibody also did not enhance IFN-γ production (p
0.05) in either group (data not shown).
Figure 2 TNF-α and IFN-γ production with or without stimulus with PPD. TNF-α and IFN-γ production was determined by ELISA in supernatants of PBMC culture from co-infected patients and patients with tuberculosis only unstimulated (more ...)
The expression of mRNA for IL-12 in unstimulated cultures and the production of IFN-γ in PBMC cultures stimulated with PPD and in cultures with PPD plus exogenous addition of IL-12 are shown in Figure
. The expression of mRNA for IL-12 in unstimulated cultures was lower in tuberculosis patients with or without co-infection with HTLV-1 than in seronegative controls (Figure
A). Exogenous addition of IL-12 in cultures stimulated with PPD enhanced IFN-γ production similarly in both groups (Figures
, B and C).
Figure 3 Expression of mRNA for IL-12 and IFN-γ production after exogenous addition of PPD plus IL-12. mRNA for IL-12 was determined by RT-PCR in unstimulated cultures of PBMC from seronegative healthy subjects, co-infected patients, and patients with (more ...)