Yellow fever in the diagnostics laboratory

Abstract

Yellow fever (YF) remains a public health issue in endemic areas despite the availability of a safe and effective vaccine. In 2015-2016, urban outbreaks of YF were declared in Angola and the Democratic Republic of Congo, and a sylvatic outbreak has been ongoing in Brazil since December 2016. Of great concern is the risk of urban transmission cycles taking hold in Brazil and the possible spread to countries with susceptible populations and competent vectors. Vaccination remains the cornerstone of an outbreak response, but a low vaccine stockpile has forced a sparing-dose strategy, which has thus far been implemented in affected African countries and now in Brazil. Accurate laboratory confirmation of cases is critical for efficient outbreak control. A dearth of validated commercial assays for YF, however, and the shortcomings of serological methods make it challenging to implement YF diagnostics outside of reference laboratories. We examine the advantages and drawbacks of existing assays to identify the barriers to timely and efficient laboratory diagnosis. We stress the need to develop new diagnostic tools to meet current challenges in the fight against YF.

Fig. 1

Yellow fever phylogenetic analysis showing major YFV genotypes, based on alignment of a 1428 nt region of the prM-E junction region for 36 representative African and American YFV strains (Table 1) using the Maximum Likelihood method based on the general time reversible model (GTR). Individual strains are defined by name and country/year of isolation. Bootstrap values (500 replicates) for major branches are indicated

Fig. 2. Alignment of the primers and probes of shortlisted assays against relevant YFV target sequences.

The figure is restricted to the four assays described in references^,,,, which generated the fewest mismatches overall in the comparison with the reference set of 61 YFV genomic sequences (Table 1). Perfectly matched YFV sequences are not shown. Primer and probe sequences are written 5′ to 3′ except for the reverse primers at the right edge of the figure, which are represented by the reverse-complement of the oligonucleotide sequence

Fig. 3. Alignment of the primers and probes of shortlisted assays against relevant YFV target sequences.

The figure is restricted to the two assays described in references^,, which generated the fewest mismatches overall in the comparison with the reference set of 61 YFV genomic sequences (Table 1). Perfectly matched YFV sequences are not shown. Primer and probe sequences are written 5′ to 3′ except for the reverse primers at the right edge of the figure, which are represented by the reverse-complement of the oligonucleotide sequence