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Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013.

ABSTRACT: Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5'-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5'UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.

SUBMITTER: Sadeuh-Mba SA

PROVIDER: S-EPMC6505894 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:The establishment of the influenza sentinel surveillance system in Kinshasa, Bas Congo, Maniema, Katanga, and Kasai Provinces allowed generation of important data on the molecular epidemiology of human influenza viruses circulating in the Democratic Republic of Congo (DRC). However, some challenges still exist, including the need for extending the influenza surveillance to more provinces. This study describes the pattern of influenza virus circulating in DRC during 2015. METHODOLOGY:Nasopharyngeal swabs were collected from January to December 2015 from outpatients with influenza-like illness (ILI) and in all hospitalized patients with Severe Acute Respiratory Infection (SARI). Molecular analysis was done to determine influenza type and subtype at the National Reference Laboratory (NRL) in Kinshasa using real time reverse transcription-polymerase chain reaction (rRT-PCR). Analysis of antiviral resistance by enzyme inhibition assay and nucleotide sequencing was performed by the Collaborating center in the USA (CDC, Atlanta). RESULTS:Out of 2,376 nasopharyngeal swabs collected from patients, 218 (9.1%) were positive for influenza virus. Among the positive samples, 149 were characterized as influenza virus type A (Flu A), 67 as type B (Flu B) and 2 mixed infections (Flu A and B). Flu A subtypes detected were H3N2 and H1N1. The Yamagata strain of Flu B was detected among patients in the country. Individuals aged between 5 and 14 years accounted for the largest age group affected by influenza virus. All influenza viruses detected were found to be sensitive to antiviral drugs such as oseltamivar, zanamivir, peramivir and laninamivar. CONCLUSION:The present study documented the possible involvement of both circulation of Flu A and B viruses in human respiratory infection in certain DRC provinces during 2015. This study emphasises the need to extend the influenza surveillance to other provinces for a better understanding of the epidemiology of influenza in DRC. It is envisioned that such a system would lead to improved disease control and patient management.

Project description:Peste des petits ruminants (PPR) is an acute, contagious viral disease of small ruminants, goats and sheep. The Democratic Republic of the Congo (DRC) was a PPR-free country until 2007, although in 2006, scare alerts were received from the east and the southwest of the country, reporting repeated mortalities, specifically in goats. In 2008, PPR outbreaks were seen in several villages in the west, leading to structured veterinary field operations. Blood, swabs and pathological specimens consisting of tissues from lungs, spleens, lymph nodes, kidneys, livers and hearts were ethically collected from clinically infected and/or dead animals, as appropriate, in 35 districts. Epidemiological information relating to major risk factors and socio-economic impact was progressively collected, revealing the deaths of 744,527 goats, which converted to a trade value of USD 35,674,600. Samples from infected and dead animals were routinely analyzed by the Central Veterinary Laboratory at Kinshasa for diagnosis, and after official declaration of PPR outbreaks by the FAO in July 2012, selected tissue samples were sent to The Pirbright Institute, United Kingdom, for genotyping. As a result of surveys undertaken between 2008 and 2012, PPR virus (PPRV)-specific antibodies were detected in 25 locations out of 33 tested (75.7%); PPRV nucleic acid was detected in 25 locations out of 35 (71.4%); and a typical clinical picture of PPR was observed in 23 locations out of 35 (65.7%). Analysis of the partial and full genome sequences of PPR viruses (PPRVs) obtained from lymphoid tissues of dead goats collected in Tshela in the DRC in 2012 confirmed the circulation of lineage IV PPRV, showing the highest homology (99.6-100%) with the viruses circulating in the neighboring countries of Gabon, in the Aboumi outbreak in 2011, and Nigeria (99.3% homology) in 2013, although recent outbreaks in 2016 and 2018 in the western part of the DRC that borders with East Africa demonstrated circulation of lineage II and lineage III PPRV.

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Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013.

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