Discussion
Drug resistant TB has been one of the most important public health
challenges that we have faced since the early 1990s [25]. Due to the
fact that Iran is TB endemic, as well as its proximity to TB high burden
countries, several cases of DR-TB (Drug resistance TB) are reported
annually in this country [26-28]. Based on the existing information
for the new and previously reported treated cases, the MDR-TB prevalence
in Iran is reported to be 2.48% and 5%, respectively [22]. Reports
on DR-TB indicate its annual increase due to the spread of MDR-TB
strains worldwide, and in particular in the Middle-East region [29].
One of the most important DR-TB problems is the high mortality rate in
DR-TB cases and the increase of primary drug-resistant TB cases
[30]. Currently, 5 different types of DR-TB have been reported,
including mono-resistance TB, poly resistance TB, multi-drug resistance
TB (MDR-TB), extensively-drug resistance TB (XDR-TB) and totally-drug
resistance TB (TDR-TB), for which monitoring, controlling and preventing
the prevalence of MDR-TB, XDR-TB and TDR-TB are of great importance
[31].
The present study was a rare report about cervical lymphadenitis caused
by primary MDR-TB strain in an infant that was born from TB patient
mother. The infant was considered as MDR-TB case, while his mother was
susceptible to the first line anti-TB drugs. Fingerprinting of infant
and mother isolates showed that the mother was infected with multiple
strains, whereas the child was infected with the strains of the Beijing
genotype family. Therefore, it is more probable that the infant was
infected from mother as the congenital route. The MDR-TB strain for the
present case belonged to Beijing genotype family, which was confirmed
previously in the published Iranian reports. In a systematic review and
meta-analysis on the Iranian MDR-TB cases, Tarashi et al. (2017) found
that the distribution of Beijing genotype family is predominant
genotypes among the MDR-TB Iranian cases [32-33].
Congenital tuberculosis is occurred as a result of umbilical vein into
utero, perinatal route via ingestion or aspiration of infected amniotic
fluid or direct contact with the infected parental genital lesions.
Infected placenta is mainly the route of congenital TB in neonates that
can transmit Mtb strains to the fetal liver or lungs [34-35].
The primary TB infection symptoms can be presented as pulmonary
complication disseminated to the internal organs, cutaneous or central
nervous system [36]. According to review of the literature, Cantwell
et al. (1994) found that the age range presenting the congenital TB
symptoms is between 24-84 days. We observed the sign of TB in our case
at 55 days after his birth [37]. We also found that the mother was
infected by multiple Mtb strains. Thus, the possibility of
confronting with a congenital TB case is higher, although the boy infant
had not responded to the first-line anti tuberculosis drugs, as opposed
to his mother. Infants are more susceptible to tuberculosis due to their
lack of sufficient immunity system. There are some reports about the
cervical tuberculosis lymphadenitis in children below 1-year of age. We
report the first case of MDR-TB cervical lymphadenitis infection, which
could have occurred due to spontaneous mutations in response to the
inadequate anti-TB therapy as well as primary resistance to the Beijing
strains in Iran [38-40].
Cervical tuberculosis lymphadenitis is one of the most prevalent forms
of extra-pulmonary TB that often occurs in immunocompromised cases
[23]. Although Mtb often affects the lungs, in the
immune-compromised cases, particularly children and HIV-infected people,
TB bacilli are spread through through the lymphatic system due to the
lack of an efficient and effective TB bacilli immune system, often
occurring in the form of Cervical tuberculosis lymphadenitis [23,
41-42]. Despite the fact that the CTL cases caused by DR-TB are very
limited, but the epidemiologic importance and diagnostic difficulties of
managing and treatment of these cases are quite challenging because of
the lack of specific guidelines for the treatment, especially in the
immunocompromised patients, who do not usually have granulomatous
inflammation due to immune dysfunction. Moreover, PPD results in these
patients are negative due to a weakened immune system [23, 42].
Based on the available evidence, lung CXR is usually normal in cervical
tuberculosis lymphadenitis patients, with merely showing the
abnormalities in 24-46% of these patients [43]. So far, limited
cases of cervical tuberculosis lymphadenitis caused by DR-TB strains
have been reported, most of whom are in the TB endemic countries (Table
1).
According to the review of the literature, lymphadenopathy is the most
prevalent form of TB in the endemic TB countries, whereas infection with
DR-TB strains is rare in these countries [23], although regarding
the increased prevalence of DR-TB, increasing the number of these cases
is not unexpected in the coming years [22,42]. The most common
clinical manifestations and symptoms of cervical tuberculosis
lymphadenitis include single or multiple painless lumps,
lymphadenopathy, fistula formation (in some cases), weakness, low grade
of fever, coughing and pulmonary hilar lesion (if being involved and in
case of primary lung infection) [43-44]. Cervical tuberculosis
lymphadenitis may lead to misdiagnosis in cases with negative PPD
results, lack of evidence of lung involvement, absence of granuloma
formation in some cases, and coinfection with HIV or immune-disorder
[45]. However, no relapse in the untreated patients is observed and
mortality rate is reported to be low in the DR-TB cervical lymphadenitis
patients, although it is not being fatal if promptly diagnosed and
treated (Table 1).
Fine needle aspiration is a precise and reliable tool for cervical
tuberculosis lymphadenitis detection, that based on available sources,
their sensitivity and specificity are about 88% and 96%, respectively,
based on available sources [46]. However, according to Deveci et al.
(2016), the sensitivity of acid-fast staining and culture methods for
cervical tuberculosis lymphadenitis detection are estimated to be about
46-78% and 10-69%, respectively [47]. Culture also takes about 6-8
weeks due to the slow growth nature of Mtb and is not quite
appropriate. However, the molecular methods, particularlyIS6110 -PCR, are able to detect the cervical tuberculosis
lymphadenitis cases in a very short time with acceptable accuracy
[45-47]. According to the previous studies, the positive results of
PCR obtained by FNA on the cervical tuberculosis lymphadenitis samples
were high, being 71.4%, 76.4% and 92.1%, respectively in the three
fulfilled studies [48-49]. Drug-resistant-TB (DR-TB) CTL treatment
had a low mortality rate despite the lack of standard guidelines, and it
seems that combination therapy, including sinus drainage and
anti-tuberculosis drugs based on drug susceptibility testing, to have
satisfactory results and usually relapse in these cases (Table 1).