Genetic characterization of treponema pallidum isolates and detection of viruses of human health relevance in Free-ranging non-human primates of Tanzania

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Date

2020

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Publisher

Sokoine University of Agriculture

Abstract

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.

Description

PhD Thesis

Keywords

Genetic, Treponema pallidum, Viruses, Human health, Free-ranging, Tanzania

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