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).