In this study, PTB frequency was found to be 5.4% of all the forms of tuberculosis. This markedly contrasts with 81.4% found in the general population in our country and with 80% of cases published in other pediatric series [10, 11]. This could be explained based on inclusion of only children without clinical signs of extra pulmonary disease and for the fact that PTB patients are only hospitalized when they present the severe form of the disease. It is worthwhile to point out that in this age group, the systemic form of the disease is important, reason why the exclusion drastically affected the frequency.
In this study, a greater percentage of PTB case (51.7%) was found in less than five-year old group which drastically reduced in older patients above 15 years. This coincides with 60% reported in the literature for less than 15-year-old patients indicating that in pediatric population, the risk of developing the disease is greater in the first years of life [12]. We did not find significant differences in age-disease distribution among the patients however; the period covering the first 6 years witnessed a greater number of cases with a reduction of up to 85% in the following years. This could explain the declining number of cases reported in the general population.
Even though acquired immunodeficiencies constitute a risk factor for the development of tuberculosis, in our series, only two cases had HIV (2.3%), which is comparable to nearly 3% reported in developed countries [9, 13] and sharply contrasts with 12 to 37% reported in developing countries [14, 15]. The explanation of this is farfetched, even when it has been reported that in adult patient with HIV, reactivation constitutes the most important pathogenic mechanism of tuberculosis, and that in countries with less prevalence of the disease, tuberculosis in general is acquired at later ages and reactivation is a very rare event in children, which could explain the low prevalence of HIV in this series [10].
Epidemiological contact of TB was found in 41.9% of our PTB cases with children less than one-year old accounting for 52.8% of the cases but with lesser contacts established. As usual, the source of infection was associated in most cases (75%) to the “caretaker”. The percentage of familiar contacts was significantly less in children of 15-year old and more due to increased extra domiciliary contacts in this age group. However, in the present series, we did not find such contacts, similar to what is reported in other series [16].
The protective clinical efficacy of BCG vaccine has been a matter of controversy, although it is accepted that this is greater for miliary and meningeal TB than for pulmonary form [17, 18]. In this study, it is important to note the tendency of greater number of positive cultures in patients with history of BCG immunization, where we supposed to have a lesser mycobacterial replication and in consequence a lesser number of bacilli.
In our series, all the patients were symptomatic when the diagnosis was made, similar to that described by Vallejo et al. in Texas, where in a series of 47 infants, 79% of the cases, were diagnosed by the presence of symptoms, and only19% was by epidemiological history [16]. However, this data contrasts with the reports of Sánchez-Albisua et al. in Madrid, where in a series of 173 children under 15 years, 59% of the cases were identified by contact [17], probably in relation to an active search of the contacts, situation that allows the identification of cases in very early stages of the disease [19].
We found nonspecific signs and symptoms with fever and cough being the most consistent clinical manifestations, independently of age, which account for 94.3% of the reason for medical consult. Nonetheless, loss of weight was seen in most of the patients independently of the age. Expectoration and hemoptysis were significantly more frequent in the group older than 14 years, which is similar to the findings in adults with PTB [20]. PPD was positive in an important proportion of the cases (59.2%), mostly in children older than 1 year. Again, this is similar to that reported by other authors (35-60%), probably due to inclusion of only patients with PTB in our series which is different from other series where different forms of tuberculosis (extra pulmonary or disseminated) were included with positive PPD of 32% to 50% [21, 22].
It is of interest to note that in this study PPD was negative in 2 (including a patient with positive culture) of the 3 patients older than 15 years with normal state of nutrition and one with an identified anergizing disease which could be attributed to lack of PPD response as stated by other authors who found lack of response to PPD in approximately 10% of the patients without any underlying disease with tuberculosis documented by culture [21].
Radiological studies play an important role in the diagnosis of tuberculosis in pediatric age. Although there can be some differences in its interpretation, the findings suggestive of PTB in children under 5 years old are of great support for its diagnosis. In this series, the image of consolidation was a frequent finding in all age groups and was significantly more frequent in patients older than 5 years, in contrast with mediastinal lymphadenopathies, which were present in children below this age coinciding with what was reported by other authors. The miliary pattern was seen in only 6.9% of the cases, mainly in patients below 5 years old, with a clear prevalence in those less than 1 year old, in whom the disseminated disease is more frequent. Pleural effusion is infrequent in pediatric age but in our series it was seen in 14.3% of the cases [23]. The presence of calcifications and caverns were significantly more frequent in patients above 14 years old due to the fact that it is an infrequent complication of primary tuberculosis [10, 12, 16, 21–23]. It has been identified that the presence of fever and cough of 2 or more weeks, plus a positive PPD of 10 or more millimeters, have a positive predictive value of 73% with a sensitivity of 44% for tuberculosis confirmed by culture [24]. Based on this, it was suggested that children fulfilling 2 of these 3 criteria should be evaluated with chest X-ray and ZN positive [24, 25].
The microbiological diagnosis is denoted with difficulties because the sensitivity of ZN positive is from 20 to 25%. In this study however, ZN was positive in 51.7%. With respect to this, it is important to note that this was performed in children older than 5 years old in whom PTB forms such as caverns contain a greater number of mycobacteria in contrast with the type of lesions found in children less than this age where the TB is habitually paucibacillary. Mycobacterium identified by culture is present in 30.4% of the cases. These results are comparable to variations in different reports, where culture was found positive in 20 to 75% of cases [20, 26, 27]. PCR value in diagnosis of tuberculosis in pediatrics is still controversial due to the false positives, mainly in countries with high endemicity for tuberculosis, and to the false negatives that are reported. In this study it was positive in 83.3% of the cases documented by culture [28–30].
Antituberculous treatment was well tolerated in most cases. Patients responded well to the treatment even when there was one death, precisely a boy with HIV and multidrug resistant tuberculosis without adherence to treatment. The other 2 deaths were not attributable to tuberculosis. 54.1% of the children were treated for 6 months with clinical and radiological response similar to those who were treated from 9 to 24 months (treatment for such long periods of time was administered in patients with underlying immunosuppressive diseases), without clinical evidence of related complications.