A two years old child of Rumanian origins, born in Italy to a TB-affected mother, was admitted to our division because of persistent fever (39 C). Chest radiography revealed a typical miliary reticulo-nodular pattern (Figure 2).
IGRA tests, as well as Ziehl Neelsen staining of the smears, cultures and nucleic acid amplification (collected by undertaking three early morning gastric aspirate for up to three consecutives days), gave positive results for Mtb. Anti-TB therapy with INH, RMP, PZD and Etambutol (ETM) was begun.
Nevertheless, only few hours after the beginning of therapy, the patient presented drowsiness and a diminished level of consciousness, horizontal nystagmus, trismus, frontal release signs (suck), miosis with loss of reaction to light. Cerebrospinal fluid examination was performed and revealed the presence of Mtb nucleic acid. A non-contrast head CT scan showed two hypodense space-occupying lesions in the subcortical white matter and in the knee of the right internal capsule.
TB meningitis was therefore diagnosed and corticosteroid therapy was begun with a rapid improvement of his clinical conditions. However, a left hemiparesis appeared. Contrast-enhanced brain magnetic resonance imaging (MRI), performed one week after, showed meningeal enhancement, a reduced measures of the space-occupying lesion in the subcortical white matter, abnormal enhancement of basal cisterns and decreased diameter of the focalised lesion of the right internal capsule knee (Figure 3). A few weeks later, the child presented vomiting, apathy and drowsiness. The non-contrast head CT scan highlighted the presence of obstructive hydrocephalus and signs of intracranial hypertension (enlarged ventricles and peri-ventricular hypodensities).
The child underwent ventricular-peritoneal derivation and symptoms resolution was achieved.
The last contrast-enhanced MRI showed enlarged ventricles with no signs of intracranial hypertension and the presence of a focal lesion at the knee of the right internal capsule. An angio-RMI study showed no vascular abnormalities. To date, the patient shows good clinical conditions, although the left hemiparesis, requiring long term physiotherapy, is still present.
An erosion of a parenchymal focus of TB into a blood or lymphatic vessel may result in dissemination of the bacilli and in a miliary pattern, with small nodules on the chest x-ray. The TB meningitis is the most severe extra-pulmonary TB-related complication, that results from hematogenous spread of primary or postprimary pulmonary disease or from the rupture of a subependymal tubercle into the subarachnoid space in a time of 3-6 months generally. A lot of cases show old pulmonary lesions or miliary pattern on chest radiograph. In fact, it's accepted a close concordance between TB meningitis and miliary TB in young children.
Because of the haematogenous spread of bacilli during a lung miliary pattern, it is important to considerate the possibility of an extra-pulmonary involvement.
In clinical practice two different types of Central Nervous System involvement may develop: tuberculoma and meningitis.
Tuberculoma usually shows a good response to treatment, with resolution of acute signs and symptoms, even if with the possibility of sequelae depending on the first focal lesion. In contrast, the treatment of a meningeal involvement is still a clinical challenge. In fact, in our case, the anti-tubercular therapy was effective against lung and brain lesions, but the meningeal involvement showed a progression, up to meningeal thickening and hydrocephalus.
The accelerating clinical illness usually correlates with the development of hydrocephalus, as in the present case. Even the use of high-dose corticosteroids may not stop meningeal inflammation. However, clinical trials demonstrated that corticosteroids should be routinely used in HIV-negative patients with TB meningitis to reduce death and disabling residual neurological deficits among survivors, although sometimes more aggressive anti-inflammatory drugs may be needed. Sometimes profound abnormalities in electrolyte metabolism may be observed, due to salt wasting syndrome or development of syndrome of inappropriate antidiuretic hormone secretion. We concluded the management of our patient with an angio-RMI study. TB can be considered as a vasculitis, and a significant percentage of children with TB generally presents ischemic brainstem lesions. Moreover, studies are necessary to show the exact meaning of these lesions, their implication for the patient's management and the possible use of anti-inflammatory and of anti-platelets agents to prevent neurological lesions and sequelae.
The present case deals with a premature female infant, born in Italy from a Nigerian mother with HIV infection and pulmonary TB during pregnancy. The infant came to our attention, after having been in another hospital, because of pulmonary TB and HIV infection.
At birth, she had an episode of asphyxia and was transferred to a Neonatal Intensive Care Unit (NICU). Two months after discharge from NICU, the child presented with weight loss, diarrhea, dehydration and acute severe dyspnea. Admitted to the Pediatric Intensive Care Unit, she was intubated and ventilated. Here the diagnosis of congenital HIV and TB was achieved on the bases of positive bacterioscopic analysis and PCR on the bronchoalveolar lavage, positive IGRA, positive bacterioscopic and cultures analysis on urine, positive cultures on the gastric aspirates and the presence of typical lesions in pulmonary CT scan. Abdominal US revealed two hypoechoic hepatic lesions and a hypoechoic spleen area. A case of congenital TB was then suspected because of urine positivity for Mtb and both liver and spleen hypoecoic lesions.
She was admitted to our division in order to continue the anti-TB (INH, PZD, and ETM), corticosteroid and highly-active anti-retroviral therapy (HAART). An antibiotic prophylaxis with cotrimoxazole was also begun.
The 6 months follow up shows a child in good clinical conditions.
Congenital TB is a rare manifestation of TB.
Clinical manifestations of congenital and neonatal TB are non-specific, they usually present like neonatal sepsis and diagnosis is often delayed. Low birth weight and prematurity are common features of HIV and TB infected neonates born to HIV-infected mothers with TB.
Cantwell et al proposed diagnostic criteria for congenital TB. Among them we mention the onset of TB clinical manifestations in the first two weeks of life, the presence of a primary focus or granulomas in the liver and the demonstration of placenta and genital area contamination. These criteria increase diagnostic sensitivity, but the diagnosis remains difficult since confirmation of the primary complex or detection of granulomas in the liver has to be carried out by biopsy, which is not always available. In our case a liver biopsy was never performed.
The co-infection between TBC and HIV really represents a clinical challenge for physicians, especially in childhood. Impressively, HIV-infected children demonstrate an increased risk of rapid disease progression, unsatisfactory treatment response and TB recurrence; moreover, TB mortality is six times higher among HIV-infected children than among uninfected ones. It has been showed that a close link exists between clinical developments of these two infectious diseases. On one hand TB is able to induce a quicker progression of HIV disease by increasing viral replication and reducing CD4+ T-cells counts. On the other hand, since protective immunity to TB infection depends on the CD4+ T-cell subset, HIV infected children with decreased CD4+ T-cells count are at greater risk of TB disease progression.
TB treatment of HIV-infected children is a challenge, too. The lack of clinical trials in children creates concerns regarding common toxicities, drug interactions, side effects and the best time for the introduction of HAART following TB diagnosis. In fact, the management of TB in HIV-infected children usually deviates from standard protocols. Despite local and international guidelines, therapy often has to be individualized.
Regarding the best time to introduce HAART, WHO recommends to begin the treatment at different time points, starting earlier in the more immunocompromised children or where response to TB treatment is poor.
The management of TB-HIV co-infected children is of special difficulty due to the peculiar immunologic background and the extensive drug-drug interaction, and so requires a broader and specific discussion, which is above the purpose of this manuscript.
The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee.
Informed consent has been obtained from all individuals included in this study.