Seroepidemiological Survey of Cytomegalovirus Infection among Pregnant Women in Sudan

The human Cytomegalovirus (HCMV) or human herpesvirus 5 is one of the leading causes of congenital infections. Pregnant women can be infected with HCMV by a primary disease, reactivation, or reinfection of a different HCMV strain during pregnancy (De Paschale et al. 2009; van Zuylen et al. 2014; Alvarado-Esquivel et al. 2018). HCMV has different genotypes based on glycoproteins in the envelope (gB (UL55) and gH (UL75)), which might influence the severity of diseases (de Vries et al. 2013; Alwan et al. 2019). For instance, gB1 and gB2 genotypes are linked to hepatosplenomegaly and hearing impairment. Also, the gB2 genotype was connected to an abnormality in the image of ultrasound and/or magnetic resonance in fetuses and newborns congenitally infected, unlike gB4, which might not reveal an abnormal image (Novak et al. 2008; Brañas et al. 2015).

HCMV has different spreading routes that directly contribute to its high prevalence; these can be via body fluids like saliva, breastfeeding, sexual contact, and placental transfer or through organ transplantation, including blood transfusion, solid-organ transplant, or hematopoietic stem cell transplantation. Moreover, due to the lack of a specific drug for HCMV infection and no vaccine, along with the less knowledge about congenital HCMV in health care and the public, besides, asymptomatic infection in newborns, so they will not be defined at birth, all these factors significantly contributed to the magnitude of HCMV infection as a great health problem (Shedlock et al. 2012; Manicklal et al. 2013; Alwan et al. 2019).

HCMV viral transmissions occur among all age groups, races, and socioeconomic classes throughout the modernised and developing parts of the world (Emmanuel and Ogbu 2017). HCMV seroprevalence ranges from 40 % and may reach up to 100%, especially in high-risk populations like HIV-infected patients and those on immunosuppressive treatment (Delvincourt et al. 2014).

Feto-maternal transmission can occur during pregnancy through the placenta, during delivery through direct contact with maternal cervical secretions and blood, and postnatal via breast milk (Bhide and Papageorghiou 2008). Strikingly, transplacental transmission can occur even in women with pre-existing seroimmunity to CMV, which can be explained either by viral reactivation or infection with a new, different strain of CMV (reinfection) during the pregnancy (Hassan et al. 2014).

Infants infected with the virus can present many symptoms and signs, from petechial rash, jaundice, and hepatosplenomegaly to more severe manifestations, including neurologic abnormalities such as microcephaly and lethargy. Also, chorioretinitis and optic atrophy occur in approximately 10% of symptomatic infants (Boppana et al. 2013). Vertical transmission of the virus during primary HCMV infection is about 30–35%, while for secondary infection and reactivation, it is in the range of 1.1–1.7%, which is a significantly lower transmission rate (Marsico and Kimberlin 2017).

CMV among congenitally-infected infants can cause permanent morbidities such as deafness, blindness, and mental retardation (Kenneson and Cannon 2007; Yinon et al. 2010; Simonazzi et al. 2017). In addition, HCMV infection during pregnancy is the most common congenital infection worldwide, with an estimated incidence of approximately 0.6 to 0.7% of all live births in the developed world. The prevalence of congenital HCMV infection in developing countries significantly varies within and between countries, ranging from 0.6 to 6.1% of all live births (Lanzieri et al. 2014; Marsico and Kimberlin 2017).

Sudan is one of the developing countries and consists of 18 states. Out of 91 pregnant women, 67 (73.6%) were HCMV IgG positive in the Khartoum State, a capital city (Ali 2016). In Western Sudan, out of 231 pregnant women, 167 (72.2%) were HCMV IgG positive (Hamdan et al. 2011). However, there need to be more documentation systems to monitor the seroprevalence of HCMV in the other region of Sudan. Therefore, this study was conducted to screen the seroprevalence of HCMV IgG and IgM antibodies among pregnant women in the Kassala State and River Nile State and to correlate possible risk factors, including age, educational level, past miscarriages, gestational stage of pregnancy, and place of residence. This study will help understand the possible transmission risk factors and preventive measures.

Human cytomegalovirus (HCMV) is the most common cause of congenitally acquired infections. The present study aimed to detect HCMV antibodies in pregnant women in the River Nile State, located in the Eastern North and the Kassala State, one of the rural areas in Eastern Sudan, where daily hygiene status is inadequate. Among 184 blood specimens tested for HCMV IgG, 170 (92.4%) were positive, in line with previous reports that rural residents are 92% seropositive for the virus (Hassan et al. 2014). This high percentage of seroprevalence was slightly lower than the result obtained in Nigeria, where 97.2% of participants were CMV IgG positive (Akinbami et al. 2011), Northern Turkey – 97.3% (Uyar et al. 2008), Palestine – 96.6% (Neirukh et al. 2013), and in Asir Region, Kingdom of Saudi Arabia the seroprevalence was 95.7–100% (Almaghrabi et al. 2019). These seroprevalence results differ slightly from that recorded for the central Mexican city of Aguascalientes, where it was 89.6% (Alvarado-Esquivel et al. 2018). This discrepancy may be attributed to the different endemicity of CMV infections in these countries (Lantos et al. 2017; Udeze et al. 2018).

Interestingly, there was a different percentage of seroprevalence of HCMV in pregnant women within Sudanese States. A similar study was conducted in Khartoum State and found that out of 91 pregnant women, 67 (73.6%) were CMV IgG positive (Ali 2016). Another study in Western Sudan to estimate the seroprevalence of HCMV in pregnant women demonstrated that out of 231 pregnant women, 167 (72.2%) were CMV IgG positive (Hamdan et al. 2011). Socioeconomic status and ethnicity explain these differences within a country (van Zuylen et al. 2014).

When analyze the results by the gestational trimester, the positive percentage of IgM in the first trimester was 8 (21.6%). Primary HCMV infection is critical because it is a significant risk factor for vertical transmission of HCMV infection to newborns (Umeh et al. 2015). The prevalence of congenital CMV transmission rates is 50% when primary CMV infection occurs in pregnant women and less than 2% in non-primary infection of pregnant women (Davis et al. 2017). Moreover, HCMV causes congenital malformations and miscarriages when it is a primary infection during the first trimester. The risk of developing fetal manifestations of the disease is more significant when the primary infection occurs during the first thirteen weeks of pregnancy (De Paschale et al. 2009).

In this study, the women from the River Nile State who had a history of miscarriage screened positive for HCMV IgG and IgM and were significantly associated with HCMV infection (p ≤ 0.05). These findings may indicate that HCMV could be one of the significant risk factors for miscarriage among pregnant women in Sudan. Illiteracy and low education levels are associated with an increased likelihood of contracting HCMV through direct contact with infectious secretions from their children and poor hygienic conditions in their homes. Low socioeconomic status also contributes significantly to acquiring HCMV infection (Hassan et al. 2014).

In comparing the two States, the results indicated that the prevalence of CMV IgG in the River Nile State was lower than in the Kassala State. This study also documented that the prevalence of HCMV infection in Sudan varies across states; this difference might be due to lifestyle because in the Kassala State, all participants live in rural areas and are not educated. Also, these differences were due to socioeconomic status and ethnicity within the country (van Zuylen et al. 2014).

HCMV infection during pregnancy is associated with severe neurologic deficits in newborns, infants, and immunocompromised individuals (Zhang and Fang 2019). It is, therefore, necessary to prevent the disease rather than treat it. We can do prevention by screening blood to avoid CMV transmission (Emmanuel and Ogbu 2017). In addition, there is an urgent need for increasing awareness in society that infectious body fluids such as saliva and urine of infected children are an essential source of HCMV infection during pregnancy. Also, promoting preventive attitudes and practices (i.e., washing hands whenever they come into contact with a child's saliva or urine, not sharing drinking glasses or eating utensils with infants, and not kissing infants on the mouth or cheek) will be generally acceptable and effective measurements (Lazzarotto et al. 2011). Therefore, pregnant women must be protected from HCMV infection through proper hygiene and behavior; pregnant women must be educated about the consequences of acquiring HCMV infection; routine screening for HCMV infection should be performed during pregnancy in the obstetric unit. Moreover, antiviral prophylaxis should be given to reduce the risk of HCMV infection. In addition, recent studies have shown that the administration of hyper immunoglobulin (CMV HIG) to pregnant women exposed to CMV significantly reduces the rate of vertical CMV transmission and improves neonatal outcomes (van Zuylen et al. 2014).

This study demonstrated a higher seroprevalence rate of HCMV among pregnant women in the Kassala State (rural) than in the River Nile State (urban). The high percentage of illiterate women living in rural areas makes it possible to reduce the incidence of HCMV infection in pregnant women by improving their knowledge, behavior, and practice regarding the virus's transmission route, which may translate into lower rates of congenital diseases in their infants.