Primary EBV infection is usually asymptomatic and may progress to benign lymphoproliferative disease called infectious mononucleosis (IM), especially in late childhood or early adulthood in developing countries [<link rid="bib4">4</link>].
Infectious mononucleosis is characterized by significant clinical polymorphisms in which factors such as age, immune status and comorbidities have been described as parameters in clinical evolution, which can vary from asymptomatic infection to more severe conditions. It can be evidenced by acute complications, such as multiple organ failure, disseminated intravascular coagulation, ulcer/perforation of digestive tract, coronary artery aneurysm, lymphomas and lymphohistiocytes and EBV-associated hemophagocytosis [<link rid="bib19">19</link>, <link rid="bib20">20</link>].
Mendoza et al. (2008) confirmed that EBV infection has an incubation period ranging from 4–6 weeks with prodromal symptoms of asthenia, anorexia, headache and chills, which often precede the signs and symptoms of mononucleosis: such as fever (which can reach 39–40 °C) accompanied by pharyngotonsillitis and lymphadenopathy [<link rid="bib21">21</link>, <link rid="bib22">22</link>, <link rid="bib23">23</link>]. The results obtained in the present study agree with that ones, since the 76 patients with EBV analyzed, fever was the main clinical finding in 65.8% (50/76), cervical lymphadenomegaly in 60.5% (46/76), pharyngitis in 19.7% (15/76), arthralgia in 17.0% (13/76) and headache in 9.2% (7/76).
Regarding the type of EBV infection, there are two different types of EBV [<link rid="bib24">24</link>]. EBV types are related to variation in the EBNA2 and EBNA3 gene sequences, commonly known as types 1 and 2 [<link rid="bib17">17</link>, <link rid="bib25">25</link>].
Studies conducted in other countries have demonstrated the predominance of EBV1 infection in China with rates of 76.3%, Argentina in 75.9%, Sweden in 67.0% and Hong Kong 57.0% [<link rid="bib26">26</link>, <link rid="bib27">27</link>, <link rid="bib28">28</link>, <link rid="bib29">29</link>].
Our findings demonstrated that EBV1 was the most frequent type (82.9%- 63/76) detected by PCR using EBNA 3C gene, in the infectious mononucleosis cases reported in the metropolitan region of Belém, Pará, Brazil, being in 71.1% (54/76) alone and 11.8% (9/76) associated with EBV2. It is worth mentioning that these results, obtained in symptomatic patients, were pioneers in this region. In an investigation conducted with Chinese individuals using the same technique showed slightly smaller results for EBV1 (76.3%- 45/59) . In this context, other studies carried out by Deng et al. (2014) with Japanese patients and by Smatti et al. (2017) in Qatar also describe EBV1 with rates of 73.3% (107/146) and 72.5% (37/51) respectively [<link rid="bib30">30</link>, <link rid="bib31">31</link>].
Regarding EBV2, it was detected in 28.9% (22/76) of the positive EBV cases, with 17.1% (13/76) alone and 11.8% (9/76) co-infected with EBV1 (Table 1). This value was higher than those described by Deng et al., 2014 [<link rid="bib30">30</link>] and Correa et al., 2004 [<link rid="bib27">27</link>] in the Japan (18.5%- 27/146) and Argentina (14.6%- 29/199) respectively. A lower frequency, about 3.5%, was verified in Qatar by Smatti et al., 2017 . It is important to mention that the positivity observed by EBV2, in the age group > 10–15 was very higher (75%- 6/8), when compared with EBV1 (37.5%- 3/8). However, these cases were detected in different months of these years.
In this investigation we verified that EBV2 infection demonstrated a longer clinical course when compared to EBV1, with the presence of fever on average of 17.6 days (range: 1–90 days), while EBV1 14.7 days (range: 1 to 30 days); the high rate of 62.5% observed to EBV2 in the age group of > 10–15 years was characterized by the presence of fever and lymphadenopathy. The EBV-2 has frequently been associated with special clinical conditions such as patients with weakened immune systems, for example HIV carriers or individuals with oncogenic processes. In vitro, several studies have recorded a low frequency of EBV2 in B lymphocytes demonstrating a reduced or less efficient capacity for replication in cell cultures [<link rid="bib17">17</link>].
The presence of multiple infections by EBV1 + EBV2 was observed in 11.8% of the positive cases of infectious mononucleosis, where 20.0% (2/10) occurred in children less than five years old (Table 1). This fact emphasize that co-infections are not exclusive to immunocompromised individuals. This association was also verified by Correa et al., 2004, in 10.5% of the healthy individuals participated of a study conducted in Argentina. The co-infection may occur by the simultaneous transmission of both genotypes or by the contact with two people infected with distinct strain [<link rid="bib27">27</link>].
Another finding that stood out in the present investigation was the occurrence of alterations in transaminases (aspartate aminotransferase - AST, alanine aminotransferase - ALT and gamma-glutamyl transferase - GGT), that varied from 19.4–41.7% (Table 2) for EBV1 in over 14 years old, with expression of these hepatic enzymes, a fact also documented in the studies of Herbing et al. [<link rid="bib32">32</link>].
It is known that eventually small changes in transaminase enzyme value can occur in normal individuals without infection (less than twice the reference value) while in individuals with EBV-infective mononucleosis, these values can increase 5 to 10 times the reference values and it may evolve for a fulminate hepatitis frame [<link rid="bib33">33</link>].
In addition to such observations, in this study the mean transferase average was statistically significant in > 14 years of age with infections for EBV1 (P < 0.05) when compared to EBV2 and EBV1 + EBV2 co-infection. Similar data have also been documented by Zhang et al. (2018) when compared infectious mononucleosis cases and control ones, as they observed high levels of ALT, AST and GGT only in cases of infectious mononucleosis, indicating that transferases levels should also be observed as a risk alert durig infection caused by MI [<link rid="bib34">34</link>].