A One Health systems approach to the epidemiology, management, and regulatory control of bovine brucellosis at the human-cattle-farm interface in Gauteng, South Africa

Abstract

Background and Introduction Human brucellosis, a neglected zoonotic disease of global public health importance, can be prevented by controlling the disease in livestock hosts. In South Africa (SA) there has been an increasing number of reported bovine brucellosis outbreaks with a concomitant lack of increasing numbers of human brucellosis cases. Objective and aim The objective of study was to determine the risk factors of bovine brucellosis as well as the epidemiology of brucellosis in cattle handlers and veterinary field officials working at the human-cattle-farm interface in Gauteng province, by undertaking an interdisciplinary field investigation under the precept of “One Health”. We aimed to understand the increase of reported numbers of bovine brucellosis outbreaks and concomitant lack of increasing numbers of human brucellosis cases. Method A narrative review of South African literature on brucellosis was firstly conducted. We then analysed a dataset of bovine brucellosis laboratory test results from 2013-2018. A case-control study was conducted to identify herd management risk factors and symptoms of bovine brucellosis in the province. All herds in Gauteng that participated in the programme between 2014–2016 were eligible for this study. Farms were categorised as either case—when two or more cattle tested seropositive, or control, following routine regulatory screening using the Rose Bengal test (RBT), and confirmation of reactors with the complement fixation (CFT) test. Finally, a cross-sectional study of cattle handlers on case farms were tested for brucellosis using four commercially available serological tests: the RBT and IgM ELISA, the IgG ELISA, and an immunocapture agglutination (BrucellaCapt) test. A subset of cattle handlers on control farms and veterinary officials from the three State Vet Areas of the province were also tested. Seroprevalence was measured according to each test. Furthermore, seroprevalence is reported for five mutually exclusive combinations of test results, indicative of infection evolution from short to long, in this group of persons. These combinations were: (i) RBT positive AND IgM ELISA positive AND IgG ELISA negative, (ii) RBT negative AND IgM ELISA positive AND IgG ELISA positive, (iii) RBT positive AND IgM ELISA positive AND IgG ELISA positive, (iv) RBT positive AND IgM ELISA negative AND IgG ELISA positive, and (v) RBT negative AND IgM ELISA negative AND IgG ELISA positive. Seropositive reactors on the BrucellaCapt test were allocated to the group defined by the outcomes of the RBT, IgM ELISA and IgG ELISA. Risk factors and symptoms associated with infection of short and long evolution as well as inactive/resolved infection or exposure were explored using univariate and multi-level multivariable logistic regression. Knowledge of brucellosis and health seeking response to brucellosis-like symptoms in this group were also described. Results From 1928-2016, 32 articles were published on human or bovine brucellosis in SA. Bovine brucellosis outbreaks were detected from 1906 in the Johannesburg area of SA and the first case of human brucellosis, reported in 1924, was caused by B. abortus. Since 1959, only one further serological survey in people, conducted in 2001 was reported. The cattle prevalence for bovine brucellosis reported, decreased from 19.6% in 1934 to 5.6% in 1980. In 1990, the national herd prevalence was reported to be 14.7%. Since 1990, there has been no further report on a national or provincial estimate of herd or cattle prevalence for bovine brucellosis. Analysis of bovine brucellosis laboratory test reports from 2013-2018, for Gauteng province, revealed no significant change in prevalence of Brucella reactor herds (mean=22.1%) or within-herd seroprevalence (mean=7.4%). However, Randfontein and Germiston State Vet Areas had significantly (p<0.05) higher odds of reactor herds than the Pretoria State Vet Area. Reactor herds were also associated with increased herd size (p<0.001). Additionally, Germiston and Randfontein both had within-herd prevalence count ratios 1.5 times greater than the Pretoria State Vet Area (p<0.001) and larger herd sizes were associated with lower within-herd prevalence (p<0.001). Herd management factors associated (p<0.05) with being a Brucella infected herd were: being a government-sponsored farm, beef vs. dairy herd, open vs closed herd and the presence of antelope on the farm. Seroprevalence amongst farm workers on case farms (n=30 farms) ranged from 4.0% (BrucellaCapt) to 16.7% (IgG ELISA), compared to control farms (n=11 farms), where this seroprevalence ranged from 1.9% (BrucellaCapt) to 5.7% (IgG ELISA). Overall, 5.7% (13/230) of persons tested were seropositive to the RBT and IgM ELISA and IgG ELISA tests and 3.9% (9/230) were seropositive to all four serological tests. Farm workers on control farms presented with antibody profiles of short to longer evolution, compared to a more spread-out profile of infection evolution amongst farm workers on control farms. The difference in seroprevalence amongst farm workers between case and control farms for all the test combinations was not significant. However, seroprevalence amongst veterinary officials was significantly greater compared to farm workers on case farm for the RBT+ IgM- IgG+ outcome (OR=11.1, 95% CI: 2.5 – 49.9, p=0.002) and for the RBT- IgM- IgG+ outcome (OR=6.3, 95%CI: 2.3-17.3, p<0.001). Univariate analysis of symptoms associated with infection of short evolution (RBT, IgM and IgG ELISA seropositive), long evolution (IgM ELISA seronegative and RBT and IgG ELISA seropositive) and inactive/resolved infection or exposure (RBT and IgM seronegative and IgG seropositive), showed weak evidence of an association between reported generalized aching and infection of short duration (OR=4.8, 95%CI: 0.4-27.9, p=0.103), and strong evidence for an association between reported joint pain and infection of long duration (OR=5.1, 95%CI: 0.9-33.3, p=0.030). Mixed effects multivariable logistic models fit to identify risk factors associated with infection of short evolution (RBT, IgM ELISA and IgG ELISA seropositive), long evolution (RBT and IgG ELISA seropositive and IgM seronegative) and for likely inactive or resolved infection (RBT and IgM ELISA seronegative and IgG ELISA seropositive) identified an association between the handling of afterbirth or placenta (OR=8.9, 95% CI: 1.0-81.1, p=0.052) and strong evidence for an association between slaughter of cattle (OR=5.3, 95% CI: 1.4-19.6, p=0.013) and infection of a short evolution. Evidence of a weak association was found between infections of a long evolution and veterinary officials compared to farm workers exposed to seropositive herds (OR=4.1, 95%CI: 0.2-8.1, p=0.049). However, there was strong evidence of an association between inactive/resolved infection or exposure and veterinary officials compared to those exposed to seropositive herds (OR=7.0, 95%CI: 2.4- 20.2, p<0.001), whilst handling of afterbirth or placenta was associated with non-reactors in this group (OR=3.9, 95%CI: 1.3-11.3, p=0.012). Only 20.7% (42/203) of cattle handlers knew that B. abortus can cause abortions in cattle, can cause calves to be born weak and can also be in a herd without causing abortions. Furthermore, whilst 36.9% (75/203) knew that bovine brucellosis can cause disease in people, only 16.3% (33/203) reported knowing the human symptoms of disease. In contrast 63% (17/27) of veterinary officials knew the symptoms of bovine brucellosis and 100% knew it to be a zoonotic disease, but only 89% (24/27) knew the symptoms of human disease. Despite having greater awareness of the zoonotic nature of bovine brucellosis and human symptoms of the disease, only 22.2% (6/27) of veterinary officials would opt to visit a clinic, doctor or hospital in response to self-experienced brucellosis like symptoms, compared to 74.9% (152/203) of cattle handlers (p < 0.001). Furthermore, 53% (8/15) of BrucellaCapt seropositive persons reported to either pray, self-medicate or ignore brucellosis like symptoms experienced instead of visiting a clinic, doctor or hospital. This may indicate a proportion of