Usutu virus, a mosquito-borne flavivirus, was recently detected in a specimen taken from a man in southern France in 2016. This is only the 22nd documented case of Usutu virus disease in humans. The virus was first discovered in South Africa in 1959 and is maintained in bird reservoirs. The first human case was identified in the Central African Republic in 1981. The virus was first detected in Europe in 2001 in wild bird populations in Austria, and the continent’s first documented human cases were in Italy in 2009. These European cases were also the first to exhibit neurological manifestation of the disease, as the only two previous cases in Africa exhibited fever, rash, and jaundice. This relatively unknown and emerging zoonotic virus highlights the importance of vector-borne disease surveillance for human health.

Newly Identified Human Case

Usutu virus is a neurotropic virus, meaning that it has the capacity to affect the nervous system. In humans, it has resulted in symptoms ranging from fever to meningoencephalitis, though in most of these cases, patients also suffered from comorbidities. At this time, Usutu virus has not been observed to exhibit person-to-person transmission, although similar viruses have demonstrated this capability (eg, sexual transmission in Zika). The newly identified case had no documented history of recent travel, and it is believed that he acquired the infection locally. Usutu virus has been determined to be endemic in several European countries and was recently found to be circulating in France.

This most recent Usutu virus infection was identified through a retrospective study that analyzed the cerebrospinal fluid collected from patients in 2016 in two towns in southern France. The specimens that were tested were collected as part of a surveillance for arbovirus infections that is conducted annually in the area from May-November. The man originally presented with acute onset facial paralysis (or Bell’s Palsy), droopy eyelids, and distorted taste sensation in November 2016. After three days, the patient was admitted to a regional hospital, where he developed paresthesia (ie, “pins and needles” sensation) in his right arm and leg. After three days in the hospital, the patient was discharged, and his symptoms faded after a few weeks. When all laboratory diagnostic tests results were negative, he was diagnosed with idiopathic facial paralysis—ie, facial paralysis of unknown origin.

Outstanding Questions

A 2011 study of the Usutu virus in Africa noted the “striking” fact that the virus had only been isolated in African countries with entomological surveillance programs, raising the prospect that the geographic distribution of the virus could be substantially wider than previously reported. Similarly, it is theorized that the virus has been introduced from Africa into Europe in multiple events starting approximately 50 years ago. In fact, a 2013 study determined that a die-off of wild birds in Italy in 1996 was actually caused by Usutu virus, six years before it was first identified on the continent. The investigation was conducted only after researchers identified commonalities between recent Usutu-related die-offs and historical events. Without accurate surveillance data, how can we know the true geographic distribution of the pathogen and, therefore, the disease risk?

Conducting proactive surveillance (eg, actively looking for infections in animals and humans) for vector-borne diseases can be important to determining the true burden of disease within a population, as many of those infected exhibit nonspecific symptoms and exposure to the virus can be difficult to identify. Without accurate data regarding the geographic range of a given disease, it is difficult to effectively implement public health, clinical, and public education efforts. Populations may be at elevated risk for infection, and clinicians may not be actively considering these diseases when diagnosing and treating patients, placing them at further risk. The implementation of robust and comprehensive surveillance systems, particularly for vector-borne diseases, can provide such data and improve our ability to detect the emergence of pathogens in new geographic areas or populations.

Similarly, the variation in clinical presentation of Usutu virus infection compounds disease detection and surveillance efforts. There seems to be a difference in the clinical manifestation of the disease between the cases in Africa and those in Europe. As noted above, the initial two cases in Africa presented with fever, rash, and jaundice, whereas the European infections have been associated with more severe neurological symptoms, including encephalitis and meningoencephalitis. This distinction, however, is based on a very small sample size, including only 2 cases in Africa. Interestingly, several European countries have experienced high-mortality events in birds as well, whereas Spain and Africa have not. What is the cause for this difference in disease severity? In fact, one phylogenetic study suggests that the virus is evolving independently in Europe and Africa, resulting in distinct circulating strains, which could potentially point toward a cause. Considering the very low number of identified cases, however, considerable further research is required to make any determination.

The variation in clinical presentation also poses a risk of misdiagnosis, particularly considering that some of the symptoms are similar to a myriad of other diseases. The fact that this most recent case of Usutu virus infection in France was not detected until a retrospective study was performed 2 years later is a clear example of the potential for Usutu virus, and similar pathogens, to enter human populations undetected. Only 22 cases of human Usutu virus have been reported—and only two in Africa—but it is certainly possible that many more cases have gone, and will go, undiagnosed. Again, reliable data on the geographic spread of the virus is critical to informing clinicians of the risk so that they can include Usutu virus infection in their differential diagnosis and to educating the public so that they can take proper protective measures.

Conclusion

As noted above, vector-borne surveillance programs have been critical in detecting Usutu virus circulation in animal populations as well as detecting human cases. Accurate information about infectious disease risks enables health officials and clinicians to better protect the public’s health, and robust, proactive surveillance systems are vital to obtaining this information. While often underappreciated as tools for protecting human health, animal and vector-borne disease surveillance systems provide data and insight into human health risks that may otherwise go uncollected.

 

Photo courtesy of Pixabay.

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