Tratamiento de meningitis tuberculosa en paciente HIV negativo, posible reacción paradojal / Possible paradoxical reaction to treatment of tubercular meningitis in an HIV negative patient

La respuesta paradojal al tratamiento tuberculoso es la aparición de manifestaciones clínico-radiológicas nuevas, o el empeoramiento de las previas, luego de una mejoría inicial con el tratamiento específico. Se puede observar en 6-30% de los casos de tuberculosis meníngea. Es una reacción inmunológica exagerada y debe tenerse presente ya que su tratamiento se basa en el uso de inmunomoduladores y no en el cambio de las drogas antituberculosas. Presentamos el caso de una paciente adulta HIV negativa con meningitis tuberculosa que, luego de una adecuada respuesta inicial al tratamiento, intercurre a las 10 semanas con una reacción paradojal tratada satisfactoriamente con corticoides.

The paradoxical response to tuberculosis treatment consists in the appearance of new clinical or radiologic manifestations or worsening of previous injuries after an initial improvement with anti-tuberculosis therapy. It can be observed in 6 to 30 percent of the cases of tubercular meningitis. It is the consequence of an exaggerated immune reaction that should be considered since the treatment is based on the use of immunomodulators and not in the change of anti-tuberculous drugs. We present the case of an HIV negative adult with tuberculous meningitis with a good initial response to specific therapy who showed, 10 weeks later, a paradoxical reaction to treatment that responded successfully to corticosteroids.

Evaluation of Lionex TB kits and mycobacterial antigens for IgG and IgA detection in cerebrospinal fluid from tuberculosis meningitis patients

To evaluate commercial Lionex TB together with four antigens of Mycobacterium tuberculosis (MPT-64, MT10.3, 16 kDa and 38 kDa) for IgG and IgA cerebrospinal fluid (CSF) detection in the diagnosis of tuberculosis meningitis (TBM) with CSF negative acid-fast bacilli staining, 19 cases of TBM, 64 cases of other infectious meningoencephalitis and 73 cases of other neurological disorders were tested by enzyme linked immunosorbent assay. IgA-MPT-64 and IgG Lionex showed the highest sensitivities, specificities, positive predictive value and negative predictive value (63.2 percent, 47.4 percent; 95 percent, 93.7 percent; 40 percent, 98 percent and 28.4 percent, 97.1 percent, respectively). However, while grey zone was 12.7 percent and 6 percent, respectively, lowering sensitivity but maintains high specificity (> 95 percent). High protein concentration in CSF was associated with antibody positivity CSF/HIV+ which did not influence the sensitivity of both tests. To our knowledge, this is the first description of IgA-MPT-64 and IgG Lionex antibodies in CSF-TBM and, although there is good specificity, adjustments are needed based on antigen composition to enhance sensitivity.

CD4+ cell counts in patients with different clinical manifestations of tuberculosis

Tuberculosis is the prototype of infections that require a cellular immune response for their control. It has been shown that CD4+ T-lymphocytes are most important in the protective response against Mycobacterium tuberculosis. CD8+ T-lymphocytes are also important for effective T-cell immune response. This study compares CD4+ and CD8+ baseline values in patients with different manifestations of tuberculosis. CD4+ and CD8+ in three groups of patients with tuberculosis (pulmonary, lymphadenitis, meningitis/milliary involvement) and a group of healthy volunteers were enumerated using flowcytometry. Twenty-six patients with pulmonary tuberculosis, 10 with adenitis, 16 with meningitis or milliary tuberculosis and 16 healthy volunteers entered the study. Mean CD4 in meningitis/milliary group was significantly lower than all other groups (p<0.05). Mean CD4 counts of patients with pulmonary tuberculosis was also significantly lower than control group (p=0.01). Mean CD8 in meningitis/milliary group was significantly lower than control group (p=0.02). No relation was found between results of TSTs and CD4 values in three groups. CD4 depletion is an expectable phenomenon in patients with tuberculosis. This study shows that patients with more severe form of disease had the lowest number of both CD4 and CD8 cells which can be a sign of suppressed cellular immunity in these patients.

ELISA of IgG antibody to Mycobacterium tuberculosis antigen-5, PPD in CSF in tuberculous meningitis patients.

IgG antibody to M. tuberculosis antigen-5 and tuberculin purified protein derivative (PPD) was measured by enzyme linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) specimens of 55 patients with tuberculous meningitis (TBM) and 55 patients with non-tuberculous neurological diseases (control group). The geometric mean antibody titre in CSF specimens of TBM patients was 82.4 with antigen-5 and 96.5 with PPD. In the control group, the geometric mean antibody titres for these antigens in CSF specimens were 4.6 and 10.8 respectively. The antibody titres did not show any correlation with tuberculin reactor status, duration of chemotherapy and IgG levels in CSF specimens in patients with TBM. At dilution end point 1:80, specificity of the assay was 100 per cent with antigen-5 and sensitivity of the assay was 70.9 per cent. False positivity observed in the control group with PPD antigen could be eliminated in 1:80 dilution in the assay with antigen-5. Antigen-5 is more specific than PPD antigen for the diagnosis of tuberculous meningitis.

Adult tuberculous meningitis. An immunological study.

In adult tuberculous meningitis (10), delayed skin hypersensitivity to DNCB was significantly impaired, whereas to tuberculin not altered. Lymphocyte migration (LMI) index was lower in comparison with pulmonary tuberculosis (20) and healthy adults (20). Lower LMI index was statistically not significant than pulmonary tuberculosis. Serum IgG and IgM levels were higher than in healthy adults. In comparison with pulmonary tuberculosis, only IgM levels were raised. We conclude that in adult tuberculous meningitis, cell mediated immune response is impaired and non-specific antibody response is increased than pulmonary tuberculosis and healthy adults.

Inmunoglobulinas en líquidos cefalorraquídeo y suero de pacientes con meningitis tuberculosa / Inmunoglobulins in cerebrospinal fluid and serum of patients with tuberculous meningitis

Se realizaron determinaciones de las concentraciones séricas y en líquido cefalorraquídeo de IgG, IgA, e IgM por medio de nefelometría y se calcularon los valores absolutos y normalizados con base en los valores esperados en población normal, así como con el índice LCR/suero en: a) veinte pacientes con meningitis tuberculosa (M-TBC) comprobados por hallazgos bacteriológicos y/o autopsia; b) ocho pacientes con cuadro clínico de meningitis tuberculosa, en los cuales no se encontró el microorganismo; c) catorce pacientes cuyas evolución clínica se asemejó a la meningitis tuberosa pero luego se esclareció otra patologia y d) como controles 16 sujetos sin sintomatología ni signología meníngea y con citoquímico normal del LCR. Teniendo como base los valores establecidos en el grupo control, se apreció un gran aumento de las tres proteínas estudiadas en LCR en sus índices respectivos en los grupos de M-TBC. En el gupo con otros diagnósticos la IgA presentó valores muy elevados en LCR, mientras que para la IgG y la IgM los aumentos fueron moderados. Las concentraciones séricas de IgG e IgA fueron normales en todos los grupos de pacientes y la de IgM presentó un ligero aumento en M-TBC y en otras patologías. La edad en los controles correlacionó con los valores de IgG en el LCR y en menor grado con los de IgA e IgM. Igualmente los índices de IgG e IgM correlacionaroan con los de IgA en los pacientes con M-TBC y otros diagnósticos. La elevación de las Igs en LCR no parece ser de ayuda en el diagnóstico diferencial de la M-TBC, pero sí explica parcialmente la inmunopatolgénesis de la reación inflamatoria a nivel de SNC