A Report of Zika Virus Seroprevalence in Republic of the Congo

Introduction

A like dengue virus and yellow fever virus, Zika virus (ZIKV) is a flavivirus (small enveloped RNA virus) transmitted by Aedes mosquitoes (Musso and Gubler 2016, Powell 2018). Phylogenetic analysis based on NS5 and E coding regions revealed the circulation of two distinct African and one Asian lineages (Gong et al. 2016); the latter one emerging out of Africa ∼180 years ago (Pettersson et al. 2016). Large outbreaks have not been reported so far in Africa and Asia. The first large epidemic was identified in Micronesia in 2007 (Lanciotti et al. 2008) followed by massive spread in the Pacific Islands, Latin America, and the Caribbean (Musso and Gubler 2016).

Despite the undisputable African evolutionary origin of ZIKV and its early identification in Africa ∼70 years ago (Dick et al. 1952), the extent of viral distribution and the herd immunity in African populations still remain largely unknown. However, low ZIKV seropositivity rates have been reported recently in Central Africa (Cameroon) (Gake et al. 2017), (Democratic Republic of the Congo) (Willcox et al. 2018), East Africa (Uganda) (Kayiwa et al. 2018), and West Africa (Nigeria) (Herrera et al. 2017, Mathé et al. 2018), (Senegal) (Herrera et al. 2017). In the Republic of the Congo, one serological survey was reported in 1954, describing 0.4% ZIKV seropositivity in 460 serum samples using a complement fixation test (Pellissier 1954). However, since the complement test has been described as the least sensitive serological methodology for dengue (World Health Organization 2009), and for ZIKV the test was reported to be susceptible to cross reaction with other flaviviruses (Charrel et al. 2016); a definitive conclusion with the results of complement fixation test is not achievable.

Importantly, a recent Cameroonian study suggested a (peri-)sylvatic circulation of ZIKV, in contrast with the urban circulation model reported during recent outbreaks in the Americas, implying a natural cycle including different, (peri-)sylvatic mosquito vectors (Gake et al. 2017).

Here, we present a new ZIKV seroprevalence study performed on healthy volunteer blood donors of the Republic of the Congo.

Serum samples from 386 healthy volunteer blood donors residing in urban (Brazzaville, Pointe-Noire) and rural areas (Ewo, Gamboma, Oyo, Owando) were collected between March and July 2011 (i.e., several years before the virus did spread to the Americas and caused large-scale epidemics) and first used for an Ebola virus study (Moyen et al. 2014). Informed written consent was obtained from each blood donor. The study was approved by the Congolese Research in Health Sciences Ethics Committee (N° 00000065 DGRST/CERSSA). Alike previous studies in the French West Indies (Gallian et al. 2017), Cameroon (Gake et al. 2017), Bolivia (Saba et al. 2018), and Lao PDR (Pastorino et al. 2019), samples were primarily tested with anti-NS1 ZIKV IgG ELISA (EUROIMMUN, Germany). Subsequently, non-negatives were confirmed by cytopathic effect (CPE)-based virus neutralization test (VNT) as described previously (Nurtop et al. 2018).

Among the 386 blood donors, a large majority (92.7%) were living in urban areas (68.4% in Brazzaville; 24.3% in Pointe Noire) and in a modern house (84.7%). They were 18–63 years old, with 181 (46.9%) of them being <30 years old and a median age of 24. The gender ratio (Male/Female) was 3.65. The majority of blood donors were unemployed (26.9%), and the most common occupations were manual labor (20.5%) and studentship (17.6%).

ELISA testing identified 5.7% of non-negatives (including 3.4% of positive [ratio ≥1.1] and 2.3% of equivocal samples [0.8 ≥ ratio <1.1]). After seroneutralization, ZIKV seropositivity rate was 1.8%. It was 1.1% in Brazzaville, 3.2% in Pointe-Noire (altogether 1.7% in urban areas), and 3.6% in rural areas (Fig. 1). The differences between rural and urban areas and between Brazzaville and Pointe-Noire were insignificant given the limited numbers tested. No statistical association between antibodies to ZIKV and gender, age, or occupation was detected.

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FIG. 1.

ZIKV seropositivity percentages in two cities and rural areas of Republic of the Congo. ZIKV, Zika virus.

In conclusion, our results evidence that the circulation of ZIKV in the Republic of the Congo is limited, resulting in a low level of specific immunity in the population, as previously observed in the neighboring Cameroon (Gake et al. 2017). Hence, the most probable model of virus circulation still refers to a (peri-)sylvatic natural cycle, as previously proposed in Cameroon (Gake et al. 2017), and not to an urban, dengue-like, cycle relying on transmission by domestic mosquitoes. This suggests that urban Aedes aegypti mosquitoes have not been implicated so far in epidemic transmission of ZIKV in the Republic of the Congo, possibly because their vector competence for (peri-)sylvatic ZIKV strains is limited. This obviously would deserve further experimental investigation.

Considering the low level of herd immunity in the Republic of the Congo, the outstanding question is whether epidemic transmission may occur after either importation of a ZIKV strain adapted to urban mosquitoes or the local emergence of a strain efficiently transmitted by (peri-)domestic mosquitoes.