Molecular characterisation of human rabies in Tanzania and Kenya: a case series report and phylogenetic investigation

Abstract

Background: Rabies remains a major public health problem in low- and middle-income countries. However, human rabies deaths are rarely laboratory-confirmed or sequenced, especially in Africa. Five human rabies deaths from Tanzania and Kenya were investigated and the causative rabies viruses sequenced, with the aim of identifying implications for rabies control at individual, healthcare and societal levels.

Case presentation: The epidemiological context and care of these cases was contrasting. Four had a clear history of being bitten by dogs, while one had an unclear biting history. Two individuals sought medical attention within a day of being bitten, whereas three sought care only after developing rabies symptoms. Despite seeking medical care, none of the cases received complete post-exposure prophylaxis: one patient received only tetanus vaccination, one did not complete the post-exposure vaccination regimen, one followed an off-label vaccination schedule, and two did not receive any post-exposure vaccinations before the onset of symptoms. These cases highlight serious gaps in health-seeking behaviour, and in health systems providing appropriate care following risky exposures, including in the accessibility and effectiveness of post-exposure prophylaxis as it is administered in the region.

Conclusions: The viral genomic and epidemiological data confirms dog-mediated rabies as the cause of each of these deaths. The phylogenetic investigation highlights the transboundary circulation of rabies within domestic dog populations, revealing distinct rabies virus clades with evidence of regional spread. These findings underscore the importance of coordinated cross-border control efforts between the two countries. Urgent action is needed to improve awareness around the need for emergency post-exposure vaccines that should be accessible in local communities and administered appropriately, as well as investment in coordinated dog vaccination to control dog-mediated rabies, the underlying cause of these deaths.

Keywords: Lyssavirus; East Africa; Genomic surveillance; Nanopore; Next-generation sequencing; One Health; Whole genome sequencing.

Fig. 1

Positive immunohistochemistry staining of frozen brain slides of Case 3. (A) Slides at × 40 magnification, and manual zoomed-in of cells of interest B) and C). The red stain zoomed in, indicates the presence of rabies virus antigen detected with specific antibodies (RABV-N, antibody 5DF12) and streptavidin-biotin complex staining

Fig. 2

Rabies viruses from five human rabies cases and animal rabies cases from the same viral lineages. A Sequenced cases in East Africa and B maximum likelihood tree of sequences (n = 262). Sequences from the Arctic AL1a clade (GenBank accession AB699220, AY956319, EF437215, HE802675, HE802676, KF154996, KY775603, KY775604, LT909539, LT909541 and MG099711) were used as an outgroup (not shown) to root the tree. Tips and points are coloured by lineage, with diamonds and numbers denoting the human cases (Case 1 sequence OR045959 from 27 Feb 2018, Case 2 sequence OR045960 from 18 Jul 2018, Case 3 sequence OR920212 from 16 Sep 2019, Case 4 sequence OR045927 from 29 Aug 2022, and Case 5 sequence OR045947 from 3 Oct 2022) and circles denoting animal cases. Scale in substitutions/site. Ultrafast bootstrap values of lineage-defining nodes shown

Fig. 3

Geolocations of RABV sequences and subtrees of human and animal cases in Kenya and Tanzania. A The map shows the locations of the sequenced human and animal cases from East Africa coloured by lineage. B Phylogenetic subtrees shown for lineage AF1b_A2 (n = 151, Case 1) in red, for lineage AF1a_A1.1 (n = 42, Case 2) in blue, for lineage AF1b_A1.1 (n = 53, Cases 3 and 5) in green and for lineage AF1a_C1 (n = 16, Case 5) in yellow. Human cases denoted by diamonds (OR045959, OR045960, OR920212, OR045947, and OR045927). Relevant locations labelled. Scale in substitutions/site, and outgroup rooted with ordered nodes