PhD Thesis
Treponema pallidum is a group of non-cultivable spiral bacteria that cause treponematoses
in humans in Europe and non-human primates (NHPs) since 1490s and 1960s,
respectively. In humans, T. pallidum pallidum causes syphilis, T. pallidum endemicum is
responsible for endemic syphilis and T. pallidum pertenue for yaws. The latter also infects
various NHP species in Africa and elsewhere in the world. Historically, Tanzania is among
84 yaws-endemic countries that currently have little data available due to scanty research
on treponematoses, both in humans and wild NHPs. In Tanzania, TPE infection has not
been studied in NHPs other than olive baboons of Lake Manyara and Serengeti National
Parks (Knauf, 2011; Harper et al., 2012). Therefore, the current study was conducted from
2015 to 2017 across different ecosystems of Tanzania to investigate TPE infection in 289
free-ranging NHPs (eight species) and genetically characterize the TPE isolates. Using
serologic treponemal test (Espline TP), this study detected anti- T. pallidum antibodies and
showed that Treponema pallidum (TP) infection is geographically widespread in
Tanzanian NHPs. The overall mean seropositivity was 53.3% (154/289) of which 60.7%
(82/135) were females and males 46.8% (72/154) males. The NHPs tested included: vervet
monkeys (77.8%, 35/45), olive baboons (85/137, 62.0%), yellow baboons (33/75, 44.0%)
and blue monkeys (1/15, 6.7%). Three independent PCRs (polA, tp47, and TP_0619)
confirmed these results but picked up 2 more positive cases missed by serology boosting
the positivity to about 54% of NHPs (156/289) with four out of eight species testing
positive at 11 of 14 locations. Majority of infected NHPs (59.8% ± 23.9% yellow baboons
at 6 sites; 45.6% ± 16.2% olive baboons and 31.6% ± 9.4% vervet monkeys at 9 sites) had
significantly more (p<0.001) anogenital ulcerations than orofacial lesions (3.5% olive
baboons at Lake Manyara). Presence of antibodies against T. pallidum significantly
associated with skin ulcerations in olive baboons (p<0.0001) and yellow baboons
(p=0.0185). Multi-Locus Sequence Typing (MLST) analysis of three genes (Tp0488,
Tp0548 and Tp0619) revealed genetically diverse simian TPE strains in Tanzania and all
the strains were closely related to TPE responsible for human yaws. Phylogenetic analysis
showed geographical clustering of TPE strains, suggesting rare interspecies transmission.
The strains had relative temporal stability and infection by multi-strain was evident.
Antibiotic resistance was not found in Tanzanian NHPs. Serological analysis of randomly
selected 74 NHPs using indirect immunofluorescence test (IIFT)-Chip technology
(Euroimmun), detected antibodies reactive or cross reactive with 13 full viral antigens out
of 20 that represent twelve virus families. These were: measles virus (89.2%, n=66),
mouse hepatitis virus (78.4%, n= 58), mouse rotavirus (73.0%, n= 54), H1N1 Singapore
(48.6%, n=36), yellow fever virus (37.8%, n=28), dengue virus (23.0%, n=17), adenovirus
type 3 (21.6%, n= 16) and parainfluenza 2 virus (10.8%, n=8). None of the Tanzanian
NHPs reacted with antigens from the rest seven viruses, including Ebola virus.
Seropositivity of the NHPs to T. pallidum could was not linked to reaction or crossreaction
with any of the investigated viruses. More studies to further characterize simian
and human pathogenic TPEs across Tanzania and Africa are highly recommended so as in
the use of more specific tests in studies detecting and identifying simian viruses of human
health significance.
German Research Foundation (Deutsche Forshungsgemeinschaft, DFG)