This systematic review and meta-analysis screened published literature on bovine PTB in China to evaluate factors influencing disease prevalence and to inform suitable control measures. Bovine PTB is a chronic granulomatous enteritis caused by Mycobacterium avium paratuberculosis and is widely prevalent in countries worldwide. The incidence of PTB has rapidly increased in China, with large-scale cattle farms reporting successive outbreaks. In addition, no specific drugs are available to manage the disease. Thus, in June 2022, the Ministry of Agriculture of the People's Republic of China classified PTB as a secondary animal disease, which indicated that bovine PTB constitutes an important disease that requires long-term monitoring [21].
This review analyzed 62 studies published between 1981 and 2021, documenting an overall PTB prevalence of 8.0% among 102,340 cattle in China, slightly lower than reports from other countries. PTB is particularly common in countries with developed cattle industries, such as the United Kingdom, France, Denmark, the Netherlands, Germany, the USA, Russia, Australia, Canada, and New Zealand [22, 23]. For instance, ELISA results in Colombia on asymptomatic cattle showed a 10% positivity rate for anti-MAP antibodies in asymptomatic cattle [24]. The overall apparent prevalence of MAP infection was found to be 6.3% and 18.9% at animal and herd levels, respectively, in cattle in Khartoum State[24]. In another study, Woodbine et al. [25] reported an average individual positivity rate of 7.1% and an average farm positivity rate of 76% in 114 cattle farms using ELISA in southwestern England. However, there are fewer reports of PTB in Asia and the rates vary widely from country to country. Japan has a low prevalence, with about 1,000 of the 500,000 cattle officially examined in Japan diagnosed annually with PTB [8]. The prevalence of PTB in this analysis was 8%, relatively lower than that observed in some European and American countries. For instance, Mongolia has a large cattle industry, and its PTB prevalence is only 0.84% [26].
Due to the complexity of the immune response against pathogens, different diagnostic methods have to be used based on the different infection periods because the suitability and sensitivity of the tests depend on the clinical stage of the disease [27]. In addition, the methods used to detect MAP infection have relative advantages and applications. In China, most studies have used ELISA serological methods, although a few have also used PCR and other microbiological techniques, which is consistent with a Brazilian study [28]. For example, in a study reported by Ferreira et al., an ELISA (PPA) assay was used to test 179 cattle suspected to be positive for PTB. Interestingly, a study by Echeverr et al. reported that while the detection of MAP infection by ELISA was both easy and practical, it should be used only as a screening method to identify various animals sensitized by mycobacteria, while specific diagnosis using "reference standard" methods, such as the isolation of MAP or PCR detection of MAP DNA, should be used for the confirmation [29]. Most of the samples evaluated in the present meta-analysis were sera. Another method used to detect MAP involves the analysis of the feces; however, the MAP levels in feces tend to be very low [30], which may be why serum rather than feces was chosen for MAP testing in most studies.
Sample type significantly influences MAP assay variability, with varying sensitivities observed across different samples, including serum, milk, stool, and cadaver. Serum and milk are predominantly used for (indirect) serological tests (ELISA) detecting antibodies[31], while feces and cadaver [32], in particular gut and associated lymph nodes[7, 33], are tested with molecular biological methods. In this analysis, most of the samples tested for MAP in the included studies were sera, and a meta-analysis showed that the sensitivity of ELISA was significantly higher in serum samples than in necropsy samples [34]. Overall, detecting antibodies using ELISA is considered the method of choice for diagnosing PTB for its speed and cost-effectiveness.
Seasonality significantly influences the PTB positivity rate. The analysis indicates higher PTB prevalence in autumn and winter compared to summer and spring. However, according to a report by Wolf et al. [35], samples collected in the spring and summer had a higher chance of testing positive for MAP than samples collected in the winter. This suggests that seasonal variations in temperature and humidity may affect the viability of MAP bacteria in environmental samples. This could be attributed to the influence of differences in climate between countries. According to Zare et al. [36], both the season and the animals' age also profoundly affect MAP infection. This is consistent with prior studies reported in China on the potential impact of seasonal factors on MAP infection rates.
The study revealed a higher pooled prevalence of PTB in calves (0–12 months of age) and adult cattle (> 24 months of age) at 15% (95% CI: 9–18) compared to young cattle (13–24 months of age) at 4% (95% CI: 1–6). Since newborns have a certain amount of maternal antibodies in their bodies, the interference of maternal antibodies cannot be ruled out by the method of antibody detection [37]. Furthermore, calves may become infected from the mother in utero [8]. Interestingly, several studies have shown that calves are more susceptible to MAP infection [38], which could be through the milk contaminated with MAP, or contact with feces containing MAP, in addition, it has been reported that adult cows and calves are equally susceptible to MAP, which is not quite what we expected. [39]. Unfortunately, only a small fraction of our statistical studies of MAP testing in calves have considered maternal antibody interference. Diagnostic methods and studies should be refined to enhance the accuracy of future PTB prevalence surveys.
In addition, the average herd size is also an important factor in the pooling positivity of bovine PTB, and we find that the positivity is relatively higher for average herd sizes between 500 and 1,000 cattle than for herd sizes that include less than 500 or more than 1,000 cattle. Furthermore, a previous study observed a minimal association between average herd size and infections by mycobacterial species other than MAP [30]. However, Corbett et al. [40] reported that larger herds (> 200 cows) were more likely to be MAP-positive than smaller herds. This observation is consistent with the results of our study, where the prevalence of MAP-positive is higher in medium-sized herds compared to smaller herds.
Dairy cattle had a higher prevalence of PTB (8%, 95%CI: 10–12) compared to dual-purpose cattle (3%, 95%CI: 1–5) and beef cattle (6%, 95%CI: 4–9), possibly due to the limited number of studies on PTB in Chinese dual-purpose cattle (yaks) [41]. In addition, susceptibility to MAP infection can also be genetically influenced. It has been found that worldwide, the incidence of PTB is lower in beef cattle than in dairy cattle [42], which is consistent with the findings of our study. This discrepancy might be attributed to the shorter feeding cycles of beef cattle compared to the longer cycles in dairy cows, potentially increasing infection risks [43]. At the same time, farming practices have an impact on PTB prevalence. In addition, most highland yaks are raised free-range, whereas dairy and beef cattle are usually intensively farmed at greater densities than dual-purpose cattle (yaks). This study analyzed the rates of bovine PTB infection in dairy, dual-purpose cattle, and beef cattle in China; however, due to the small number of studies on bovine PTB in dual-purpose cattle (yaks) in China, the results on yaks may have limitations, although the results nevertheless provide important reference data for the study of dual-purpose cattle PTB infection.
This meta-analysis offers a comprehensive review of PTB infection in Chinese cattle. Several limitations must be acknowledged. First, the 62 papers included were sourced from six large databases, with not all applicable data points contributing to a lack of qualified literature. Second, the small sample sizes in the included studies may have contributed to unstable results in overall estimates and subgroup analyses. In general, differences in the results obtained by different authors may be influenced by factors such as the stage of infection, age of the animal, level of shedding of the organism, whether or not lactation is occurring, antibody concentration, and the sensitivity of different ELISA [40]. Therefore, factors such as organism shedding levels, antibody concentration, and maternal antibody interference should be considered when comparing PTB prevalence results. The lack of comprehensive literature limited this analysis, omitting some potential risk factors, including the failure to exclude maternal antibody interference in calves, which may introduce false positives. Despite these limitations, the meta-analysis sheds light on the overall prevalence and trends of PTB infections in China during the survey period.