COVID-19 can delay the timely diagnosis of musculoskeletal brucellosis: A summary of evidence and recommendations for healthcare practitioners and health bodies.

Dear Editor,

Brucellosis is a bacterial zoonotic infection with an incidence reaching up to 200 in 100.000 in endemic regions. The disease is prevalent in rural and remote areas of the Mediterranean and the Arabic peninsula, where residents are in close contact with bovine, cattle, dogs, sheep and camels [1]. The emergence of the COVID-19 pandemic has further restricted the - already limited - access of these populations to healthcare since Spring 2020. It is quite likely that a considerable number of brucellosis cases received no or delayed diagnosis or were treated as potential COVID-19 cases, given the similarities in clinical presentation (fatigue, fever, musculoskeletal pain, respiratory symptoms).

Although brucellosis is rarely lethal, it can cause long-lasting symptoms such as recurrent fevers, heart inflammation, orchitis, joint pain, and fatigue. Chronic musculoskeletal sequalae of brucellosis occur in up to 50% of those with chronic disease [2], resulting in occupational impairment, decreased income and deteriorated personal and family health. While relevant evidence is limited, the potential burden of non–properly treated brucellosis can evolve in a considerable public health issue in the near future. The authors provide a summary of the existing knowledge and outline a strategy for the prevention and early diagnosis of brucellosis in rural and remote areas during the COVID-19 pandemic.

A quick literature search in Pubmed/Medline reveals the lack of epidemiological studies concerning the impact of COVID-19 on the timely diagnosis of brucellosis. To date, the existing knowledge boils down to a retrospective epidemiological study, two case reports and a letter to the editor.

Cheng et al. [3] (2021) investigated the incidence of natural focal diseases including Brucella in Jiangu, China during the course of the pandemic in 2020. They compared the output of a validated prediction model with the reported incidence of these diseases during these months and further juxtaposed the monthly incidence in 2020 with data from the same period between 2015-2019. The reported cases in 2020 were less than the expected ones, a finding which can be partially attributed to the restricted access of patients to the healthcare facilities for diagnosis and treatment. The same concern was expressed by Bareto-Argilagos and Rodriquez-Torrens [4] (2021) in a letter summarizing concerns from secondary research published in non–English veterinary journals. On top of the limited access to healthcare, these letters stress the potential underestimation of the disease burden associated with the contamination of dairy products with bovine Brucella abortus and the lack of diagnostic testing for B. canis.

From a clinical point of view, Güven [5] (2021) presented a diagnosis of brucellosis in a 20-year-old male with persistent complaints of joint pains and fever after resolution of a clinical and laboratory COVID-19 diagnosis, reminding that symptoms of brucellosis can mimic that of COVID-19 and can even be ignored because of SARS-CoV-2 infection history. Kucuk and Gurgun [6] (2021) described a case of an 18-year-old man with fever, dry cough, arthralgia, and hepatosplenomegaly who was hospitalized, mistakenly, with a suspected COVID-19 infection, but was eventually diagnosed with brucellosis. The exposure of this patient to a COVID-19 ward could have been avoided given that the patient resided in a rural or semi-rural area in Turkey, where brucellosis is an endemic disease. in the same applies to all areas where brucellosis is endemic such as Asia, the Mediterranean Basin, Africa, South America, Eastern Europe, and the Middle East.

The existing evidence highlights the potential underdiagnosis of Brucellosis due to limited access to healthcare facilities overwhelmed with COVID-19 and/or due to symptoms overlap with the same disease. Nevertheless, it is limited in specific regions and countries (China, Turkey) providing no data for the extent of the problem or the measures taken to mitigate this in other endemic areas. Subsequently, it is not possible to conduct relevant meta-research, which is essential to rigorously adapt the existing guidelines to the COVID-19 situation.

To the authors knowledge there were no epidemiological or clinical studies reporting specifically on musculoskeletal brucellosis, despite the potential burden arising from its delayed diagnosis and chronicity. This represents both a research and a clinical practice gap, which should be addressed with a number of measures.

First, raising awareness about brucellosis among physicians and other healthcare professionals in primary and musculoskeletal care is pivotal. This is particularly significant for those serving in endemic regions and are more likely to encounter brucellosis patients with COVID-like clinical presentation or with a coinfection. Apart from providing them with access to peer reviewed publications and relevant reports from national and local health bodies, it is important to enhance peer education with colleagues exchanging relevant experience and conducting research reporting epidemiological and clinical features of brucellosis in their region. Physiotherapists serving patients with musculoskeletal symptoms of chronic diagnosed–or even non previously diagnosed–brucellosis can provide valuable input.

Thereby, clinical practice can pay more attention to brucellosis by a) making brucellosis workup part of the standard of care examinations in endemic regions and population groups, and b) taking appropriate care and making rehabilitation accessible to individuals dwelling with chronic brucellosis amidst the COVID-19 pandemic. Musculoskeletal brucellosis deserves particular focus due to its frequency and potential long–lasting burden. The indications to provide such a workup and the specifics of chronic brucellosis care can be tailored to the clinical experience of physicians practicing in the region but needs to be properly documented and evaluated in time. In this sense, healthcare administrators need to equip laboratories in the concerned areas with the necessary resources or liaise them to centers of reference. At a higher level, authorities should allocate funding and expertise to the problem. For instance, actions for the musculoskeletal sequelae of brucellosis in EU–member states and partner countries of the Eastern Mediterranean region can be facilitated under the EU4Health, a flagship regulatory framework aiming to mitigate the burden of diseases neglected during the COVID-19 pandemic [7].

Finally, yet importantly, the public, especially those working with livestock in or from endemic areas, needs also education, so as to decrease the risk of disease transmission or early recognize the symptoms and seek appropriate care. In the context of the One Health approach, veterinarians can be involved in frequently screening animal - reservoirs for brucellosis and spreading awareness to their communities.

Overall, the COVID-19 pandemic has a negative effect on brucella diagnosis and treatment. Zoonotic diseases do not belong to the past; they exist at the present and remind us that we must take the appropriate precautions to limit their spread. As symptoms of brucellosis can mimic that of COVID-19 infection, physicians should bear in mind that they are called to make the right differential diagnosis in endemic regions. Certainly, this cause also belongs to and needs to be supported by allied healthcare professionals, healthcare administrations, stakeholders and the public.

Human and animal rights

The authors declare that the work described has not involved experimentation on humans or animals.

Informed consent and patient details

The authors declare that the work described does not involve patients or volunteers.

Disclosure of interest

The authors declare that they have no competing interest.

Funding

This work did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

All authors attest that they meet the current International Committee of Medical Journal Editors (ICMJE) criteria for Authorship.