Despite the CMV infection is widespread all over the world, the epidemiological surveillance of this virus is still neglected . Raising awareness of CMV dissemination in Brazil is imperative to combat the infection and to the clinical management of patients, especially patients with hematological diseases.
Our findings demonstrated that the CMV infection is highly prevalent among patients with hematological diseases from the Brazilian western Amazon. The study population showed a prevalence rate (91%)higher than the one observed (67.6%) in the city of Manaus . Likewise, a study carried out in the Hemotherapy and Hematology Foundation of the State of Bahia (HEMOBA), in Brazil, verified an increased prevalence rate of CMV infection (89.4%) in patients with different hematological diseases . Preeminent seropositivity for CMV infection were also observed in patients with thalassemia (94.1%) from Iran and patients with idiopathic thrombocytopenic purpura (86.4%) from China . Our results reveal a wide CMV circulation in the study population. The present study is a pioneer in describing the epidemiology of CMV infection in patients suffering from hematological diseases in the Brazilian western Amazon.
CMV infection tends to be more frequent in women than in men. This situation probably happens due to the greater susceptibility of women to sexual transmission and because women generally spend more time taking care of children (working in daycare centers or at home), as suggested by some studies [6,23]. Indeed, the risk of primary CMV infection is increased in women of childbearing age [10,24]. In this study, we did not find any correlation between sexes and susceptibility to CMV infection. Similarly, no difference in prevalence rates was observed in white and non-white individuals, even though the positivity for CMV infection has been found 30% higher in non-white people earlier . Our findings also demonstrated that elementary education and the occupation student was directly associated with the low susceptibility to CMV infection. However, the low level of education, inadequate sanitary conditions, cultural aspects, and families with a great number of individuals were already described as the main factors behind the elevated CVM prevalence rates [12,23,25]. Similarly, previous findings showed CMV prevalence ranging from 75% to 97.7% among university students from Middle West [26,27].Nevertheless, the majority of students of the study population were very young, which may explain the low susceptibility to CMV infection verified in these groups once the prevalence rates were more prominent among older people.
Sexual transmission of CMV may be facilitated by viral persistence in the female genital tract, representing an important way of transmission in sexually active adults and adolescents. In developed countries, CMV infection frequently happens in two moments: during the first 2-3 years of life or between adolescence and adulthood (16 to 30 years). In the present study, nearly half of the patients (43.7%) declared no condom usage during sexual intercourse, but we did not find any correlation between this factor and the susceptibility for CMV infection.
Our results demonstrated that the prevalence of CMV infection was greater in patients with anemia of different etiologies (93.3%), platelet diseases (94.9%), lymphoma (91.7%), and leukemia (91%). Increased prevalence of CMV infection has been previously described in patients with aplastic anemia, lymphoma, or leukemia [30–32]. In some cases, the development of these diseases and the morbimortality of patients were related to CMV infection [30,32,33]. Epidemiological studies showing CMV infection prevalence in patients with platelet disease are scarce, but the correlation between the development of thrombocytopenia and CMV infection was also reported. Although this is not a typical situation, CMV infection may lead to thrombocytopenia or thrombocytopenic purpura in healthy children during the neonatal period . In the present study, we did not analyze the association between CMV infection and the development of these diseases, nor its connection with the enhancement of patients’ morbimortality. However, the epidemiological surveillance of CMV infection in patients with hematological diseases provided by this study may be an important tool to improve their clinical management.
Detection of serum CMV IgM Abs may indicate a recent infection or a recurrent infection ( reactivation/reinfection) [35–37]. Elevated IgM and low IgG Abs titers suggest primary infection rather than reactivation or reinfection . All 17 active infections observed in our study resulted from recurrent infection since the patients presented high avidity CMV IgG. Positivity rates for CMV IgM Abs vary according to population, culture and region. A study carried out with women in reproductive age from the United States verified 2.9% of positivity for CMV IgM Abs . Pregnant women from Ireland showed 5.9% of positivity for CMV IgM Abs, whereas among patients undergoing hemodialysis from Croatia the rate observed was 2.3% [39,40]. In Brazil, 1.9% of blood donors from the Southern region showed CMV IgM positivity . The present study found a seropositivity of 5.3% for CMV IgM Abs in the study population, which is higher than most of the rates described elsewhere. These findings suggest that the hematological diseases may influence the recurrence of CMV infection.
In the context of the hematological diseases, recurrent CMV infection has been typically associated with the immunosuppression caused by therapeutic schemes. Patients suffering from chronic lymphocytic leukemia showed a CMV reactivation rate of 66% after alemtuzumab therapy . Furthermore, an elevated proportion of CMV reactivation (84.6%) was observed in children with hemoglobinopathies submitted to hematopoietic stem cell transplantation and alemtuzumab treatment . In the present study, we did not assess the clinical records of the study population to search for possible links between treatment and the recurrence of CMV infection.
Most patients positive for CMV IgM Abs suffered from ALL or anemia (various etiologies). CMV reactivation is considered elevated individuals with Leukemia. Increased rates of CMV reactivation were equally noted in patients with leukemia from India (11.3%) and Iraq (12%) [43,44]. Another study observed CMV reactivation in 66% of patients with chronic lymphocytic leukemia, after alemtuzumab therapy . These studies indicate that leukemia increases the risk of CMV recurrent infection by unknown mechanisms. However, it has been recognized that the Natural Killer (NK) cells are the key factor to combat CMV infection . Indeed, NK cell abnormality or deficiency is a risk factor for CMV reactivation . This condition could explain the occurrence of elevated CMV reactivation among patients with ALL described in this study and elsewhere, once NK cell abnormalities were already reported in these patients . In this study, we did not assess the phenotype of NK cells in patients positive for CMV IgM to verify this correlation. Yet, our findings raise the following questions: Would the patients with ALL or anemia be more prone to CMV recurrence? Are the recurrence rates associated with immunological suppression condition inflicted by ALL or Anemia diseases? A longitudinal study with a larger sample size must be done to answer this question.
In the present study, we assessed the serum levels of CMV IgG Abs according to age. The lowest serum levels were observed among children aged 1–10 years, whereas patients aged 20–29 years showed the highest IgG serum levels. A study conducted in the United States with 6.067 women aged 12–49 years demonstrated that serum levels of both IgM and IgG anti-CMV increased gradually with age progression . This correlation was equally observed in a study carried out with 3.304 individuals from Portugal .The presence of high serum levels of anti-CMV IgG antibodies has also been linked to the progression of HIV disease in patients from Uganda, Africa . Also, the clinical course of CMV infection in patients submitted to kidney transplants was associated with anti-CMV antibody titers . At present, no correlation between serum levels of anti-CMV antibodies and hematologic disease progression has been identified.
Although the present study found no significant difference in anti-CMV Ab serum levels when it was analyzed according to the hematological diseases, these serum levels may be used as an indicator of immunocompetence status in the context of hematologic disease. Also, CMV infection could be a key factor linked to patient morbidity. Thus these findings bring new insights not only regarding the epidemiological profile of CMV infection in the study population but also concerning the influence of the hematological disease on the infection recurrence and vice-versa. Therefore, the data presented here may be a starting point for new studies, especially the ones that try to elucidate the negative prognostic impact of CMV infection in patients with hematological disease.