Seroprevalence of Cytomegalovirus Infection Among a Rural Population of Côte d'Ivoire

Introduction

Human cytomegalovirus (HCMV) is a betaherpesvirus with a double-stranded DNA genome that is transmitted by contact with blood, saliva, and urine and by breastfeeding (13,16,18). It is an opportunistic herpesvirus that infects a majority of the world's population by early adulthood and causes asymptomatic latent infection in healthy individuals (23). However, it can cause severe disease in the absence of an effective immune response, especially in patients with AIDS, immune-compromised solid organ, and bone marrow allograft recipients (19,29,34). Symptoms in these subjects typically consist of indisposition, fever, hepatitis, pneumonia, gastrointestinal disease, and retinitis (24,28). HCMV seroprevalence and congenital HCMV infection depend on socioeconomic factors and hygienic practices (3,20). Of importance are also sociodemographic factors (age, sex, and ethnicity) and social environment. They differ between countries and regions (5,7,14).

HCMV seroprevalence has been investigated in several countries in the world (3,5,20), but limited data are available from African countries, especially from rural areas. In Côte d'Ivoire, a few serological studies on HCMV have been conducted in urban areas (7,14,31), but not in rural populations. The present cross-sectional study provides data about HCMV seroprevalence in the rural Taï region of Western Côte d'Ivoire.

Materials and Methods

Results

All 166 study participants were positive in the anti-HCMV IgG (100%) and 9 (5.4%) in the anti-HCMV IgM detection assays. The mean age of anti-HCMV IgM–positive subjects was 21.3 ± 13.8 years against 34.1 ± 18.4 years of IgM negative subjects. Age distribution analysis revealed that 10.2% (5/49) of the children and adolescents (1 male, 4 females) and 3.4% (4/117) of the adults (1 male, 3 females) were anti-HCMV IgM positive. This observed decrease of IgM seropositivity and the seroprevalence difference between males and females (3.8% vs. 6.1%) was not statistically significant (Table 1).

To assess whether the IgM is indicative for a primary or reactivated infection the CMV avidity index was determined for all nine IgM-positive plasma samples, and quantitative HCMV PCR was performed (Table 2). All avidity indices were above 50% suggesting absence of primary CMV infection. The PCR revealed eight aviremic subjects and only one with a low level viremia (sample ID: PAN521; viral load: 3,290 copies/mL). In a previous study, we detected HCMV DNA in two oropharyngeal swabs (sample IDs: TAI223 and PAN521) (1). Since study participant TAI223 was aviremic in the present study, we consider the detection of HCMV in the oropharynx as a local virus replication, but not as disseminated infection. Such locally restricted virus replication may cause low titer IgM values. Regarding participant PAN521, we consider this disseminated infection at low level and the positive oropharyngeal swab (1) as a putative HCMV infection in the upper respiratory tract.

In samples with high avidity index and undetectable HCMV DNA, the CMV IgM could be caused by a nonspecific cross reaction or a polyclonal stimulation following an infection with an unknown pathogen. For lymphotropic viruses like HCMV and EBV, it is well known that a polyclonal stimulation may lead to IgM reactivity against both pathogens. Therefore, we performed EBV IgM immunoblot analysis for the nine HCMV IgM–positive plasma samples (Table 2). Four were positive for EBV IgM. This likely indicates a putative polyclonal stimulation of B cells caused by EBV itself or an infection with an unknown pathogen. The remaining five samples were EBV IgM negative. Thus, a nonspecific cross reaction in the HCMV IgM immunoassay is rather likely. In case of PAN521 and TAI223, the disseminated low-level HCMV infection (PAN521) and the local virus replication (TAI223) may have caused B cell stimulation.

Discussion

This first report on HCMV seroprevalence in a rural population of Côte d'Ivoire shows that HCMV is hyperendemic in the study region (100% anti-HCMV IgG). The study participants apparently have been previously exposed to HCMV, which indicates stable circulation of HCMV in Taï National Park region. This is in accordance with previous reports on HCMV endemicity in urban populations in African countries (2,21,30,36). However, HCMV seroprevalences reported in Europe, North America, and Australia were mostly lower (40–60%) (8,9,12,17,32,33). This may be explained by differences in socioeconomic status and hygienic practices, known as determinants of HCMV transmission (4,6,23). For example, lack of access to clean drinking water likely facilitates contact with HCMV-positive secretions (35).

The presence of anti-HCMV IgM antibodies suggests active infection (23). This can be primary or reinfection with HCMV or reactivation of latent HCMV (25,27). In the present study, 9 plasma samples (5.4%) showed IgM reactivity. This is within the range of values reported in comparable studies from Sudan (2.5%), Iran (2.6%), Kenya (8.1%), and Nigeria (11%) (8,10,15,22). However, for 7/9 IgM-positive plasma samples, CMV avidity testing, combined with CMV quantitative PCR and EBV IgM testing, revealed that most of the observed IgM reactions likely originated from polyclonal B cell stimulation or from nonspecific cross reaction and not from active HCMV infection. Of note, the samples of two participants showed signs of active (plasma PAN521) or local (oral swab TAI223) infection. As reported previously, the HCMV genotypes that circulate in the investigated region do not differ from those identified in other continents (1).

Conclusion

Although the sample size of this seroepidemiological study is limited, our results indicate stable circulation of HCMV in Taï region (Western Côte d'Ivoire). This should be considered in any healthcare planning in Côte d'Ivoire. More prospective studies are required to investigate if HCMV has an impact on the health condition of rural populations in West Africa.