Lyme Disease

Lyme Disease Janet Wong, M.D.

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Lyme Disease: Epidemiology €

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Global Distribution •

Reflects distribution of Ixodes ricinus complex ticks

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North America, Europe, Asia

U.S. Distribution •

Most frequently reported vector-borne disease

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Three principle regions - Northeast, North central West Coast

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1995: 11,603 cases reported to CDC in 43 states and D.C. Overall 4.4 cases/100,000

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CT, RI, NY, N J, PA, MD, WI, MN account for 92% of cases. Connecticut accounts for 45.6 cases/100,000; MN - 5.8 cases/100,000. Nantucket County, MA - 838.8 cases/100,000

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Lyme Disease Epidemiology

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U.S. Distribution •

51% males

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0 -14 years: 24%

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35 - 49 years: 24%

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Incidence steadily increasing from 1982 -1994 -

Increased recognition, increased reporting, true increase in incidence

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Drop in incidence from 1994 to 1995 -

Decreased tick population because of environmental factors

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Decreased reporting of non-Lyme disease from GA and MO

Agent •

Borrelia burgdorferi -

Large spirochete, gram-negative, cell structure and motility is similar to other spirochetes, microaerophilic, can be grown on media; can be visualized with stining in histopathologic sections;can be visualized with light microscope,

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Three genomic groups -

Borrelia burgdorferi -- all North American cases, European arthritis

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B. garinii - Bannwarth's syndrome (tick-borne meningopolyneuritis)

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B. afzelii. Acrodermatitis chronica atrophicans

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Lyme Disease Epidemiology €

Vector •

Ixodes ricinus complex ticks

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3 Stages - larva, nymph, adult; each feeds once on a different host; life cycle span of 2 years.

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Humans most often infected from nymphs in the spring, early summer

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Less often infected by adults in the fall, winter, early spring

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Ixodes scapularis - deer tick, black-legged tick, northeast and North central U.S.

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I. pacificus - western black-legged tick, West Coast

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I. ricinus - western and central Europe

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I. persulcatus - eastern Europe and Asia

Reservoirs and Hosts •

In most areas of US, the white-footed mouse (Peromyscus leucopus) is the most important reservoir of B. burgdorferi

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White-tailed deer are important hosts but not an important reservoir

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In the West, I. pacificus primarily feed on lizards (not an important reservoir); in these areas, the dusky-footed wood rat is the most important reservoir

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Birds may serve as a host and carry infected ticks to new locations

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Humans are incidental hosts of B. burgdorferi, and they do not contribute to its maintenance in nature.

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Lyme Disease Epidemiology €

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Risk Factors •

Living in or visiting areas with high infestation with infected ticks

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Recreational activities

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Outdoor occupations

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Pets

Incidence Increasing •

Reforestation and increased deer population

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Migration of people to suburban and rural areas

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Spread of infected ticks to new geographic locations

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Lyme Disease Clinical Manifestations €

Early Localized Disease •

Erythema migrans at site of bite (80% - 90%)

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Erythema migrans lasts for 3 to 31 days (median of 7 days)

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5 to 70 cm in diameter (median of 15 cm)

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Expanding, erythematous, annular macular, painless lesion

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Resolves spontaneously within several weeks- within days with therapy

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Fatigue, malaise, fever, headache, arthralgias, myalgias, neck stiffness

Lyme Disease Clinical Manifestations €

Early Disseminated Disease •

Days to weeks after tick bite

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Secondary EM - in about half of patients, smaller, expand less; several days or even weeks after initial EM

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Fatigue, malaise, fever, headache, arthralgias, myalgias, mild neck stiffness

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Lyme Disease Clinical Manifestations €

Early Disseminated Disease •

Neurologic (15% - 20% of untreated patients) -

Meningitis - similar to other forms of aseptic meningitis

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Cranial neuritis - most commonly a peripheral facial nerve palsy; bilateral in 1/4

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Radiculoneuritis

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Bannwarth's syndrome - painful radiculoneuritis, meningitis, cranial neuropathy; uncommon in U.S.

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Cardiac Involvement (4-8% of untreated patients) -

Fluctuating degrees of atrioventricular block

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Ranges from mild first-degree to complete heart block

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Lyme Disease Clinical Manifestations €

Early Disseminated Disease •

Less common manifestations -

Eye (iritis, choroiditis, optic neuritis)

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Right upper quadrant pain with elevated transaminases

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Lyme Disease Clinical Manifestations €

Late Disease •

Months to years after tick bite

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Arthritis (60% of untreated patients) -

2 weeks to 2 years (median of 6 months)

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Arthritis is recurrent, asymmetrical, oligoarticular, swollen, warm painful.

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Affects the large joints, most often the knee (90%), lasts several days to a few weeks.

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Arthritis becomes chronic in 5% (tend to be HLA-DR4 or HLA-DR2)

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Lyme Disease Clinical Manifestations €

Late Disease •

Neurologic Manifestations -

Mild subacute encephalopathy - 2 to 3 years after onset; memory loss, mood changes, somnolence, fatigue, headache

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Polyradiculoneuropathy - spinal pain, radicular pain or distal paresthesias

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Other Manifestations of Late Disease -

Acrodermatitis chronica atrophicans almost exclusively in Europe (10% of patients)

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Eye Disease- keratitis, uveitis

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Chronic heart disease is extremely rare

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Lyme Disease Clinical Manifestations €

Congenital Disease •

Evidence from examination of placentas, fetal tissue, and live newborns suggests that B. burgdorferi can be transmitted across the placenta

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3 case reports of "congenital Lyme disease" in newborns born to women with Lyme disease during pregnancy who were either not treated or inadequately treated

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Lyme Disease Clinical Manifestations €

Congenital Disease •

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Skepticism -

Causal or coincidental association

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No definite pattern

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No inflammation

Risk of abnormal outcome with Lyme disease during pregnancy; no evidence of increased risk especially with appropriate antimicrobial therapy of maternal infection

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Lyme Disease Diagnosis €

Case Definition for the National Surveillance of Lyme Disease •

A person with erythema migrans, or

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A person with at least one late manifestation and laboratory confirmation of infection

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Erythema migrans - solitary lesion must be >5 cm

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Laboratory confirmation usually consists of demonstration of antibodies to B. burgdorferi in the patient's serum

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Lyme Disease Diagnosis •

Difficult to culture B. burgdorferi from patients' specimens or to identify B. burgdorferi in tissues with silver or immunohistochemical stains

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Diagnosis is based primarily on the presence of a characteristic clinical picture, exposure in an endemic area, and an elevated antibody response to B. burgdorferi.

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Lyme Disease Diagnosis €

Serologic Tests •

Only about 1/3 of patients with erythema migrans will have an antibody response (usually lgM)

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After 4 to 6 weeks, almost all patients will have an IgG antibody response; IgM response usually disappears by this time but may persist

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Early antimicrobial therapy can abort antibody response

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Lyme Disease Diagnosis €

Serologic Tests

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IFA

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ELISA •

Currently the best available serologic test, results of testing must be interpreted cautiously

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Not standardized; there is variation among laboratories; inaccuracy of commercial kits, false-positive and false-negative results, background level of positively in endemic areas

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Lyme Disease Diagnosis €

Serologic Tests •

Immunoblotting (Western blotting) -

More specific than ELISA; can distinguish false-positive from true-positive results

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Two-test approach (Dearborn criteria) -

All specimens positive or equivocal by a sensitive ELISA should be tested by a standardized Western immunoblot

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T-cell Lymphoproliferative Assay •

Detects cellular immune response to B. burgdorferi

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Potentially useful in small proportion of patients with seronegative Lyme disease

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Results have been inconsistent

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Not performed routinely in most labs

Polymerase Chain Reaction (PCR) •

Has been used to detect B. burgdorferi DNA in blood, CSF, urine, skin, and synovial fluid from patients with Lyme disease

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Sensitivity varies from 59% to 100%

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Major concern is false-positive results from contamination

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Lyme Disease Diagnosis €

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Synovial Fluid •

WBC usually around 30,000 but may be as high as 110,000

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Mostly neutrophils

Neurologic Disease •

Meningitis -

CSF - 30 to 200 WBC (lymphocytes)

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Normal to slightly elevated protein

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Normal glucose

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CSF index of >1 suggests intrathecal production of antibodies to B. burgdorferi

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Positive PCR

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Lyme Disease Diagnosis €

Encephalopathy •

CSF index of >1

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Elevated protein

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Positive PCR

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Abnormal MRI

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Abnormal neuropsychological testing

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Lyme Disease Treatment Early, Localized Disease

Drug(s) and Dose

>8 y

Doxycycline, 100 mg twice daily for 21 day

<8 y

Amoxicillin, 25 - 50 mg/kg/d, in 3 divided doses (maximum 1.5 g/d) for 21 days

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Lyme Disease Treatment Early, Disseminated Disease

Drug(s) and Dose

Multiple erythema migrans

Same as for early, localized disease, but for 28 days

Isolated facial nerve palsy

Same as for early, localized disease, but for 28 days

Facial nerve palsy with evidence

Same as for meningitis

of central nervous system involvement

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Lyme Disease Treatment Disease Category

Drug(s) and Dose

Carditis

Same as for early, localized disease

Mild

Same as for meningitis

Severe

Ceftriaxone, 75 -100 mg/kg, IV or IM once daily (maximum 2 g/d); or penicillin, 300,000 U/kg/d, IV, given in divided doses every 4 h (maximum, 20 million U/d) for 14 - 21 days

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Lyme Disease Treatment Disease Category

Drugs and Dose

Late disease

Same as for early, localized disease but for

Arthritis

28 days

Persistent/recurrent arthritis

Same as for meningitis

Neurologic disease

Same as for meningitis

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Personal Protection from Tick Bites €

CDC Recommendations •

Avoid tick-infested areas especially in May-July

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Wear light-colored clothing; tuck pants into socks and shirt into pants; tape area where pants and socks meet; wear long-sleeve shirts; wear a hat

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Walk in center of trail

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Inspect body carefully after being outdoors, and remove attached ticks

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Personal Protection from Tick Bites €

DEET -N, N-diethylmeta-toluamide •

Repels ticks when applied to skin or clothing- loses effect on skin in hours

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Rash and neurologic symptoms may result from prolonged, excessive use at high concentration

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Should be used no more than 20-30%, 2 -3 times/day; avoid damaged skin, hands, inhaling, ingesting; wash off with soap and water

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Permethrin - permanone •

Repellent and acaricide

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1 minute application of 0.5% to clothing

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Pets

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Tick Control €

Deer •

Important blood source and host for adult tick, not a reservoir for B. burgdorferi

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Have to totally eradicate- not practical

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Other large animals would fill void

Mice •

Host for ticks and reservoir for B. burgdorferi

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Removal not practical

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Other small mammals would fill void

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Tick Control €

Habitat Modification •

Mow vegetation, burn brush, remove leaf litter, closely cut lawn, move wood piles away from house, free rock walls of vegetation

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Biological Control •

Hunterellus hookeri -

Small wasp, one of few well-studied natural enemies of deer ticks; Female wasp oviposits in deer tick larvae, blood-fed nymph killed by emerging wasp; Scarce in most areas where deer ticks are found

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Tick Control €

General use of acaricides •

Sevin, durshan, diazinon all approved

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Often fail to penetrate foliage and reach ticks

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Because of two year life cycle and the redistribution of ticks between each host-feeding event, several applications over a large are required

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Not specific for deer ticks, expensive, environmentally unfriendly

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Management of Tick Bites €

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Tick Removal •

Use thin-tipped tweezers

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Grasp tick close to skin

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Pull straight upward, slowly and steadily

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Avoid squeezing tick

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Clean wound with antiseptic

Prophylactic Antimicrobial Therapy •

The risk of developing Lyme disease after a deer tick bite is very low.

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Given the low risk of developing Lyme disease after a recognized deer tick bite and uncertain effectiveness of prophylactic antimicrobials, routine antimicrobial prophylaxis for persons with a recognized deer tick bite is not indicated.

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Lyme Disease Vaccine •

Recombinant outer surface protein A (Osp A) (31kDa) -

Protected mice from injections of B. burgdorferi

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Protected mice from bites of infected ticks

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Smith Kline Beecham-Yale, Europe, Block Island Martha's Vineyard and Nantucket Connaught- Texas, New Mexico, NY and CT

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2 injections over 2 months, booster one year later kills B. burgdorferi in tick's gut as it takes blood meal

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Lyme Disease Prognosis €

Symptoms such as fatigue, arthralgia, and myalgia may persist for several weeks after completion of a course of antimicrobial therapy. Symptoms generally resolve spontaneously without additional antimicrobial therapy.

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No evidence that children with any manifestation of Lyme disease benefit from either prolonged (>4 weeks) or repeated courses of antimicrobial therapy.

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B. burgdorferi infections can trigger a post-infectious syndrome (eg, chronic fatigue, fibromyalgia) that does not respond to antimicrobial therapy.

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Lyme Disease Prognosis €

The most common reason for lack of response to recommended course of antimicrobial therapy in patients with apparent Lyme disease is misdiagnosis

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The long-term outcomes for children treated for Lyme disease (early localized, early disseminated, or late) are excellent

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Bibliography

Baltimore RS, Shapiro ED. Lyme disease. Pediatr in Rev 15:167-173, 1994.

Ostrov BE, Athreya BH. Lyme disease: difficulties in diagnosis and management. Pediatr Clin N. Am 38: 535-553, 1991.

Zemel LS. Lyme disease - a pediatric perspective. J Rheumatol 19 (Suppl 34): 113, 1992.

Gerber MA, Shapiro ED. Diagnosis of Lyme disease in children. J Pediatr 121: 157162, 1992.

Center for Disease control. Case definitions for public health surveillance. Morbid Mortal Weekly Rep 39: 19-21, 1990.

Centers of Disease Control. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. Morbid Mortal Weekly Rep 44: 590-591, 1995.

Rahn DW, Malawista SE. Lyme disease: recommendations for diagnosis and treatment. Ann Intern Med 114: 472-481, 1991.

Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. N Engl J Med 135: 1270-1274, 1996.

Belman AL, lyer M, Coyle PK, Dattwyler R. Neurologic manifestations in children with North American Lyme disease. Neurology 43: 2609-2614, 1993.

Shapiro ED, Gerber MA, Holabird NB, et al. A controlled trial of antimicrobial prophylaxis for Lyme disease after deer tick-bites. N Engl J Med 327: 1769-1773, 1992.

Nocton J J, Steere AC. Lyme disease. Adv Intern Med 40:69-117, 1995.

Athreya BH, Rose CD. Lyme diseasse. Curr Probl Pediatr 26: 189-207, 1996.

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