Emergency response to occupational brucellosis in a pharmaceutical manufacturing enterprise.

Dear Editor

We reported two consecutive outbreaks of occupational brucellosis among workers from 2013 to 2015 in a pharmaceutical manufacturing enterprise in East China and their successful responses using a hierarchical control strategy to prevent new outbreaks from an occupational health perspective.1 Dr Yoshida Bunkyo‐ku, who is a medical doctor from the Medical Research Institute of the Tokyo Medical and Dental University in Japan, raised several questions from a clinical medical point of view, such as the cause of the emergency, incubation period, etiology and its detection, and treatment.2 We appreciate Dr Yoshida for the academic discussion submitted and would like to provide the following supplementary information for the case report through answering his questions.

This incident was not only caused by the lack of effective personal protection equipment (PPE) for workers, but also related to the change of raw material purchasing place where the sheep placenta was purchased from a low‐prevalence area of brucellosis to a high‐prevalence area, and the lack of several key occupational disease prevention measures, such as airtight conditions, disinfection and inactivation, automation of transportation process, engineering controls, and occupational health administrative controls. These causes of this emergency were confirmed through a control effect assessment after adopting a hierarchy of exposure control strategy that consists of elimination, substitution, engineering control, administrative control, and PPE.

As Dr Yoshida mentioned, the typical incubation period of human brucellosis takes 1‐6 weeks.3 In this emergency, however, it is difficult to collect the information about the incubation period between exposure to the sheep placenta with Brucella bacteria and relevant symptom onset. In December 25, 2012, the pharmaceutical manufacturing enterprise changed the raw material purchasing place from a low‐prevalence area of brucellosis to a high‐prevalence area in China. In September 20, 2013, the first four cases of human brucellosis were diagnosed and reported. During the nearly 9 months, we were unable to determine which batches of sheep placenta were contaminated with Brucella bacteria and were put into production in this factory. As we already discussed in the case report, one drawback of this emergency response was that it could not be determined which pathogenic Brucella species was responsible for the outbreak. The samples from the original raw materials contaminated with Brucella bacteria were not available because all of the raw materials had been disposed of when the outbreak was treated as an infectious disease epidemic. Hence, etiological tests such as polymerase‐chain‐reaction (PCR) for the sheep placenta were not performed. A serum agglutination test (SAT) for the patients was used to confirm the diagnosis based on the two related standards in China, for example, the Diagnostic Criteria for Brucellosis (WS269) and the Diagnostic Criteria for Occupational Infectious Disease (GBZ227). The specific serum antibody detected with the SAT test can be an alternative brucellosis diagnostic method in the absence of blood cultures for etiological tests.4 We agree with Dr Yoshida's opinion to further perform the microplate agglutination test (MAT) or PCR test through collecting blood or bone‐marrow sample for identifying the species of Brucella responsible for the disease. Similarly, during the emergency response, we lost the opportunity to conduct these etiological tests because the biological samples were not collected and preserved in 2013 or 2015.

Currently, human brucellosis incidence has increased sharply in China. The nationwide surveillance data, which required by the “Infectious Diseases Prevention Law” in China, indicated that the total incidence rate of human brucellosis in mainland China increased from 0.92 cases/100 000 people in 2004 to 4.2 cases/100 000 people in 20145; The average annual growth rate reached 20.8% during 2003‐2014, and it will continue to rise during the next few years.6 Human brucellosis is mainly caused by the exposure to Brucella‐infected livestock, aborted materials or their products, or by consuming unpasteurized food contaminated by Brucella spp, especially milk or milk products of sheep and goats.7 Among the nine known Brucella species, Brucella melitensis is the most virulent and invasive.8 Many epidemiological studies in China revealed that 84.5% of the 634 strains isolated from the patients with brucellosis were Brucella melitensis.9

In terms of the treatment for the brucellosis in this event, a combination of doxycycline and rifampicin served as an antibiotic regimen for the seven brucellosis patients. It is a traditional treatment strategy for human brucellosis recommended by the World Health Organization (WHO). After the anti‐Brucella treatment, the patients’ clinical symptoms disappeared or were improved, indicating the traditional treatment is still effective. Dr Yoshida recommends a combination of doxycycline and streptomycin to replace the traditional treatment, which may provide a new approach to effectively treat the infectious disease.

DISCLOSURE

Approval of the research protocol: N/A. Informed consent: N/A. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. Conflict of interest: There are no conflicts of interest for this article.