Clinical features of double infection with tick-borne encephalitis and Lyme borreliosis transmitted by tick bite

Background

In Latvia and other endemic regions, a single tick bite has the potential to transmit both tick‐borne encephalitis (TBE) and Lyme borreliosis.

Objective

To analyse both the clinical features and differential diagnosis of combined tick‐borne infection with TBE and Lyme borreliosis, in 51 patients with serological evidence, of whom 69% had tick bites.

Results

Biphasic fever suggestive of TBE occurred in 55% of the patients. Meningitis occurred in 92%, with painful radicular symptoms in 39%. Muscle weakness occurred in 41%; in 29% the flaccid paralysis was compatible with TBE. Only two patients presented with the bulbar palsy typical of TBE. Typical Lyme borreliosis facial palsy occurred in three patients. Typical TBE oculomotor disturbances occurred in two. Other features typical of Lyme borreliosis detected in our patients were distal peripheral neuropathy (n = 4), arthralgia (n = 9), local erythema 1–12 days after tick bite (n = 7) and erythema chronicum migrans (n = 1). Echocardiogram abnormalities occurred in 15.

Conclusions

Patients with double infection with TBE and Lyme borreliosis fell into three main clinical groups: febrile illness, 3 (6%); meningitis, 15 (30%); central or peripheral neurological deficit (meningoencephalitis, meningomyelitis, meningoradiculitis and polyradiculoneuritis), 33 (65%). Systemic features pointing to Lyme borreliosis were found in 25 patients (49%); immunoglobulin (Ig)M antibodies to borreliosis were present in 18 of them. The clinical occurrence of both Lyme borreliosis and TBE vary after exposure to tick bite, and the neurological manifestations of each disorder vary widely, with considerable overlap. This observational study provides no evidence that co‐infection produces unusual manifestations due to unpredicted interaction between the two diseases. Patients with tick exposure presenting with acute neurological symptoms in areas endemic for both Lyme borreliosis and TBE should be investigated for both conditions. The threshold for simultaneous treatment of both conditions should be low, given the possibility of co‐occurrence and the difficulty in ascribing individual neurological manifestations to one condition or the other.The Baltic region is an endemic focus for both tick‐borne encephalitis (TBE) and Lyme borreliosis transmitted by ticks.^1,2,3,4 In Latvia, 7061 cases of TBE and 3566 cases of Lyme borreliosis were registered between 1994 and 2003, out of a population of 2.4 million. Both tick species present in Latvia, Ixodes ricinus and persulcatus, can transmit the encephalitis virus, the borreliosis spirochete and more rarely erlichiosis. A single tick bite has the potential to transmit both infections.⁵ Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness and cranial nerve involvement. Thus, differentiating between these disorders is important, given different approaches to treatment.Of the two infections, only TBE runs a biphasic course with the initial prodomal period of influenza‐like symptoms usually developing 1–2 weeks after the tick bite. Hence, after an asymptomatic period lasting 2–10 days, about a third of infected patients enter a second phase with aseptic meningitis.² Subsequently, 2–10% in Western TBE subtype or 10–25% in Eastern TBE subtype develop encephalitis, myelitis or meningoencephalomyelitis typically manifesting as combinations of flaccid paresis of the limbs, usually arms and neck, bulbar dysfunction, disorientation, aphasia and spastic paresis.^1,2 A poliomyelitis‐like syndrome is described in central European TBE.⁶ Manifestations of TBE in the Baltic may be heterogeneous, given that infection with the Western, Far Eastern and Siberian subtypes all cause human infection in Latvia.⁷ Although severe manifestations usually subside after 3–6 weeks, the convalescence period of TBE may be very long, with nearly 40% having a postencephalitic syndrome at 4 years.⁸ The uptake of TBE vaccination is increasing in the Baltic region.Classical Lyme borreliosis differs considerably from TBE and produces local and generalised forms, systemic involvement, and development over several stages. Its acute and chronic courses pose problems of diagnosis and management.^1,9 Diagnosis of neuroborreliosis requires a definite or possible tick bite, erythema migrans or seropositivity, and typical peripheral or central nervous system involvement.¹⁰ In early neuroborreliosis (2–10 weeks after tick bite) the most common neurological abnormalities are meningitis, meningoradiculoneuritis and cranial neuritis, particularly facial palsy.^1,9,10,11 Progressive chronic encephalomyelitis, polyneuritis and cerebrovascular disorders are later manifestations of Lyme borreliosis, usually occurring months after the initial infection. Neurological features are noted in 10–12% of all patients with Lyme borreliosis in Europe¹ and in 10–15% of patients in Northern America.¹¹ Neurological manifestations in 330 European patients with Lyme borreliosis included radicular pain (70%), headache (18%), peripheral paresis (45%), central paresis (4%), sensory disturbances (44%) and facial palsy (39%).¹ Borrelia infection takes a subclinical or minimally symptomatic course in up to 80% of the population after tick bites.¹² Importantly, borreliosis is treatable with antibiotics.TBE infection can be proven by specific and sensitive ELISA detection of antibody in cerebrospinal fluid (CSF), or by detection of genome through polymerase chain reaction.¹³ Serum IgM antibodies can remain positive for ⩾10 months.^2,14 By contrast, serological tests for Lyme borreliosis infection are less sensitive and specific to variable onset and occurrence of specific IgM and IgG antibodies, with recognised persistent seronegatives; direct detection of a pathogen is rarely possible, and reliance must be placed on interpreting the laboratory investigations in the light of the clinical picture.^13,15,16 Demonstration of intrathecal antibody production provides a specific test,¹⁷ but is not sensitive in detecting all forms of neuroborreliosis.¹⁵ Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness, and cranial nerve involvement. Pain, particularly in a radicular distribution, and sensory disturbance are regarded as features more typical of Lyme borreliosis than TBE.Only limited information on double infection with TBE and Lyme borreliosis is available. Single cases, small series or serologically defined series with limited clinical information are described from Germany, Slovenia, Central Russia and Finland.^{18,19,20,21,22,23,24} This retrospective clinical observational study analyses the clinical features and problems of differential diagnosis in patients with evidence of both TBE and Lyme borreliosis infection in Latvia.