Human Borrelia miyamotoi infection in the United States.

Krause PJ, Narasimhan S, Wormser GP, Rollend L, Fikrig E, Lepore T, Barbour A, Fish D. N Eng J Med 2013 Jan 17; 368(3):291-3.

Introduction

On 17th January 2013 news from America announced the discovery of ‘a new tick-borne infection that shares many similarities with Lyme disease’(1). The bacteria, which is not new, is called Borrelia miyamotoi , a relative of those which cause Lyme disease. Genetically, it is more closely related to the relapsing fever group of spirochaetes(2). Borrelia miyamotoi was first discovered in 1995 in Japan(3). Globally, it is transmitted by the same ticks that carry and transmit Lyme disease to humans.

The USA

In America, Borrelia miyamotoi was first discovered in Ixodes scapularis ticks back in 2001 by a team from Yale University(4). In addition to trans-stadial transmission (larva ->nymph ->adult), transmission from egg to larva was shown in 6-73% of the offspring of infected females, which is thought to be rare in Lyme disease. At that time the team concluded that ‘further work is needed to determine the potential public health significance of yet another zoonotic agent transmitted by this tick species.’

Europe

The first report of a B. miyamotoi -like spirochaete in an Ixodes ricinus tick in Europe was in Sweden in 2002.(5)

Evidence of human infection first came from Russia in 2011 (6). A study of 302 patients investigated for tick-borne infections showed that 17% were infected with Borrelia miyamotoi.(5) Confirmatory tests were ELISA (EUROIMMUN AG, Lübeck, Germany) and PCR. The time from tick bite to onset of symptoms (12-16 days) was longer, whereas the time from onset of symptoms to hospital admission was shorter (1-2 days), compared to Lyme disease. Erythema migrans rash was seen in only 9%, making clinical diagnosis more difficult. Apart from this, most patients presented with similar symptoms to Lyme disease, though the number and severity of symptoms was higher with B. miyamotoi . Relapsing ’flu-like illness with fevers as high as 39.5C occurred in 11% and symptoms included headache, chills, fatigue, vomiting, and myalgia. B. miyamotoi infection was treated with the same antibiotics used to treat Lyme disease: 14 days of oral doxycycline 200mg or IV ceftriaxone 2g per day. The consequences of untreated infection and any effects on pregnancy are currently uncertain. Co-infection with other tick-Borne pathogens may increase disease severity. The rate of tick infection in the area was 1-16%, which is similar to rates of infection with B. miyamotoi in ticks in Europe and America.

Current interest

The interest created in January 2013 arises from the January 2013 edition of the NEJM in which there is a case report of an ‘older immunocompromised patient’ with progressive mental deterioration who was diagnosed with meningoencephalitis caused by Borrelia miyamotoi, directly detected using microscopy and PCR of the CSF (cerebrospinal fluid).(7)

In the same issue, in a letter to the Editor, Krause et al. confirm human Borrelia miyamotoi infection in the USA, in all areas where Lyme disease is endemic.(8) Archived specimens from endemic areas (1999-2010) were tested for the presence of GlpQ antigen which is reactive to B. miyamotoi (and other relapsing fever spirochaetes) but not B. burgdorferi .(9) Results showed that 21% (n=3) of 14 patients investigated for a late spring or summer viral-like illness tested positive for this antigen, with rising convalescent antibody titres, suggesting recent infection. None were immunocompromised. Treatment was with doxycycline or amoxicillin.

Where now?

We do not know whether any of the relapsing fever Borrelia are present in the UK. B. miyamotoi appears to cause a very similar infection to that of the better known Lyme disease Borrelia (B. afzelii, B burgdorferi, B. garinii). The principle (but not the only) differences appear to be less frequently (maybe never) causing an erythema migrans rash and more frequently causing fevers. What is certain is that it is perfectly possible for a UK holidaymaker to contract this infection in Europe, and now we know also in the USA.

The Russian study(6) showed that the ELISAs currently used in Europe as a screening test for Lyme disease seem to be moderately successful at detecting B miyamotoi infections. However, we do not know whether these infections would be confirmed by an immunoblot : currently a critical step towards treatment in most of Europe. Krause et al gave no detail of their immunoblot and it is a pity that this study has been published as a letter as opposed to a peer reviewed paper which would contain corroborating data. The GlpQ antigen they report using would have reacted to other relapsing fever Borrelia as well and PCR does not appear to have been used to check, as it had been in the Russian study.

This report, therefore, simply highlights the uncertainties our recent project has confirmed:

• the species of Borrelia causing UK disease are not known
• the best test for detecting UK Borreliosis is not known
• the best treatment is not known

On we go to find more answers about the infections caused by these fascinating and complex organisms.

References

1. Yale News, January 16, 2013 http://news.yale.edu/2013/01/16/so-new-it-doesn-t-have-name-yale-researchers-discover-tick-borne-infection
2. Bunikis J, Tsao J, Garpmo U, Berglund J, Fish D, Barbour AG. Typing of Borrelia relapsing fever group strains. Emerg Infect Dis 2004Sep;10(9):1661-4.
3. Fukunaga M, Takahashi Y, Tsurata Y, Matsushita O, Ralph D, McClelland M, Nakao M. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolated from the ixodid ticks Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol. 1995 Oct; 45(4):804-10.
4. Scoles GA, Papero M, Beati L, Fish D. A relapsing fever spirochete transmitted by Ixodes scapularis ticks. Vector Borne Zoonotic Dis. 2001 Spring; 1(1):21-34.
5. Fraenkel CJ, Garpmo U, Berglund J. Determination of novel Borrelia genospecies in Swedish Ixodes ricinus ticks. J Clin Microbiol 2002 Sep; 40(9): 3308-12.
6. Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA,Toporkova MG, Maleev VV, Fish D, Krause, PJ. Humans infected with relapsing fever spirochete Borrelia miyamotoi , Russia. Emerg Infect Dis 2011 Oct; 17(10):1816-23.
7. Gugliotta JL, Goethert HK, Berardi VP, Telford SR 3rd. Meningoencephalitis from Borrelia miyamotoi in an immunocompromised patient. N Eng J Med 2013 Jan 17; 368(3): 240-5.
8. Krause PJ, Narasimhan S, Wormser GP, Rollend L, Fikrig E, Lepore T, Barbour A, Fish D. Human Borrelia miyamotoi infection in the United States. N Eng J Med 2013 Jan 17; 368(3):291-3.
9. Schwan TG, Schrumpf ME, Hinnebusch BJ, Anderson DE Jnr, Konkel ME. J Clin Microbiol 1996 Oct; 43(10): 2483-92.

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