Molecular Characterization of Human Enteroviruses in the Central African Republic: Uncovering Wide Diversity and Identification of a New Human Enterovirus A71 Genogroup

Abstract

dHuman enteroviruses (HEV) are among the most common viruses infecting humans. Their circulation has been widely studied in most parts of the world but not in sub-Saharan Africa, where poliomyelitis remains prevalent. We report here the molecular characterization of 98 nonpoliovirus (non-PV) HEV strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the Central African Republic (CAR). The isolates were typed by sequencing the VP1 coding region and sequenced further in the VP2 coding region, and phylogenetic studies were carried out. Among the 98 VP1 sequences, 3, 74, 18, and 3 were found to belong to the HEV-A, -B, -C, and -D species, respectively. Overall, 42 types were detected. In most cases, the VP2 type was correlated with that of the VP1 region. Some of the isolates belonged to lineages that also contain viruses isolated in distant countries, while others belonged to lineages containing viruses isolated only in Africa. In particular, one isolate (type EV-A71) did not fall into any of the genogroups already described, indicating the existence of a previously unknown genogroup for this type. These results illustrate the considerable diversity of HEV isolates from the stools of paralyzed children in the CAR. The presence of diverse HEV-C types makes recombination between poliovirus and other HEV-C species possible and could promote the emergence of recombinant vaccine-derived polioviruses similar to those that have been implicated in repeated poliomyelitis outbreaks in several developing countries.

High Frequency and Diversity of Species C Enteroviruses in Cameroon and Neighboring Countries

“…Lineage III includes CVA-10 strains that had been circulating in China, Japan, South Korea, and Spain from 2000 to 2010. Within this lineage, the Chadian strain showed high sequence similarity scores (93.0% and 96.6% at the nucleotide and amino acid levels, respectively) and grouped consistently with CVA-10 strain OMB-06-062, a recently reported strain from the Central African Republic (32).…”

“…Accordingly, a number of types detected in healthy children in 2008 were not found in 2009. All echovirus 7 (E-7) VP1 sequences formed a sub-Saharan cluster along with E-7 strains recently reported in the Central African Republic (32) (Fig. 2).…”

“…Strain C08-041, from Douala, was a member of genogroup C, while the second EV-A71 strain, C08-146, from Yaoundé grouped consistently with the recently reported Central African strain NMA-03-008. The latter strain, showing a high sequence similarity score of 89.6% and 97% at the nucleotide and amino acid levels, respectively, with strain C08-146, was previously shown to belong to a new EV-A71 genogroup tentatively called "genogroup E" (32). The identification of strains of this genogroup in the Central African Republic, Nigeria (32), and Cameroon indicates that it was circulating without known disease outbreaks in Africa.…”

“…Overall, five isolates of EV-D111 have been reported so far, and all of them originated from subSaharan Africa (32)(33)(34). They segregated into two reliable subclusters (Fig.…”

Éradication de la poliomyélite et émergence de poliovirus pathogènes dérivés du vaccin

“…Les résultats obtenus jusqu'à maintenant, concernant quatre pays, indiquent que les HEV-C circulent très peu en Roumanie et en Tunisie [22,23]. En revanche, des fréquences relativement élevées ont été mises en évidence en République Centrafricaine et au Cameroun [24,25]. Au Cameroun, nous nous sommes intéressés plus particulièrement à la circulation et à la diversité génétique des HEV circulant chez les enfants sains dans l'extrême nord du pays, une région limitrophe des états du Nigéria où l'émergence de cPVDV est récurrente [21].…”