Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment.

BACKGROUND: The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. METHODS: We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. FINDINGS: The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. INTERPRETATION: The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. FUNDING: Defense Biological Product Assurance Office.

Assessing the cost-effectiveness of different measles vaccination strategies for children in the Democratic Republic of Congo.

INTRODUCTION: One of the goals of the Global Measles and Rubella Strategic Plan is the reduction in global measles mortality, with high measles vaccination coverage as one of its core components. While measles mortality has been reduced more than 79%, the disease remains a major cause of childhood vaccine preventable disease burden globally. Measles immunization requires a two-dose schedule and only countries with strong, stable immunization programs can rely on routine services to deliver the second dose. In the Democratic Republic of Congo (DRC), weak health infrastructure and lack of provision of the second dose of measles vaccine necessitates the use of supplementary immunization activities (SIAs) to administer the second dose. METHODS: We modeled three vaccination strategies using an age-structured SIR (Susceptible-Infectious-Recovered) model to simulate natural measles dynamics along with the effect of immunization. We compared the cost-effectiveness of two different strategies for the second dose of Measles Containing Vaccine (MCV) to one dose of MCV through routine immunization services over a 15-year time period for a hypothetical birth cohort of 3 million children. RESULTS: Compared to strategy 1 (MCV1 only), strategy 2 (MCV2 by SIA) would prevent a total of 5,808,750 measles cases, 156,836 measles-related deaths and save U.S. $199 million. Compared to strategy 1, strategy 3 (MCV2 by RI) would prevent a total of 13,232,250 measles cases, 166,475 measles-related deaths and save U.S. $408 million. DISCUSSION: Vaccination recommendations should be tailored to each country, offering a framework where countries can adapt to local epidemiological and economical circumstances in the context of other health priorities. Our results reflect the synergistic effect of two doses of MCV and demonstrate that the most cost-effective approach to measles vaccination in DRC is to incorporate the second dose of MCV in the RI schedule provided that high enough coverage can be achieved.