INTRODUCTION:

Lyme disease is also known as Lyme borreliosis, is a form of arthritis caused by bacteria that are transmitted by deer ticks. Phytophoto dermatitis also known as Lyme disease. Deer ticks also known as lyodes tick. It is a most common and dangerous disease. It is treatable by medical professional and requires a medical diagnosis. Lyme was diagnosed based on the history of established exposure to tick bites, presence of classic signs, symptoms, serology and response to treatment. About 300000 new cases per year are recording in the world. Deer ticks can carry bacteria that cause Lyme disease.

HISTORY:

During¹ the early 19th century, Lyme disease was present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest. The early European studies of what is now known as Lyme disease described its skin manifestations. Neurological problems following tick bites were recognized starting in the 1920’s. Painful sensory radiculitis accompanied by mild meningitis following a tick bite. A large, ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. n 1930, the Swedish dermatologist Sven Hellerström was the first to propose EM and neurological symptoms following a tick bite were related. In the 1940s, German neurologist Alfred Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

EPIDEMIOLOGY:

Lyme disease² is the most common vector-borne illness in North America and Europe. The etiologic agent, Borrelia burgdorferi³ sensu lato, is transmitted to humans by certain species of Ixodes ticks, which are found widely in temperate regions of the Northern hemisphere. Clinical features are diverse, but death is rare. The risk of human infection is determined by the geographic distribution of vector tick species, ecologic factors that influence tick infection rates, and human behaviors that promote tick bite. Rates of infection are highest among children 5 to 15 years old and adults older than 50 years. More than 36000 confirmed and probable Lyme disease cases were reported in the United States in 2013.the number of the cases is estimated to be approximately 300000 per year. Cases are focussed in 14 high incidence states located in north east and north central United States. About 65000 people are affected with lyme disease every year in europe.

LYME DISEASE IN INDIA:

This case series highlights its presence in Haryana, a nonendemic zone. The first case was a 27-year-old housewife who presented with an annular erythematous patch with a central papule following an insect bite on the left upper arm. The second case was a 32-year-old farmer who gave a history of insect bite on the right arm followed by the development of an erythematous patch with a central blister. The third case, a 17-year-old boy presented with a history of tick bite over right thigh and a typical bull's eye lesion with central ulceration.

SIGNS AND SYMPTOMS OF LYME DISEASE: Lyme disease can affect multiple body systems and produce a broad range of symptoms .The incubation period from infection to onset of symptoms is one to two weeks but can be much shorted or much longer. Symptoms most often occur from month may to September because the nymphal stage of tick is responsible for most of the cases. Asymptomatic infection can exist but occur in less than 7% of the infected individuals. Based on the severity, the disease is divided into three stages. 1. Early localized infection, 2. Early disseminated infection 3. Late disseminated infection

HOW LYME DISEASE IS CAUSED:

Lyme disease⁴ is caused by spirochetal bacteria from the genus borrelias. Spirochetes are surrounded by peptidoglycan and flagella, along with an outer membrane. Because of their double membrane envelope, the Lyme related borrelia burgoferi sensu lato and show a great deal of genetic diversity. B.burdoferi sensulati is made up of 21 closely related species, but only 3 clearly cause Lyme disease i.e., B.burgiferisensu stricto, B.afzelii, B.garinii.

Fig no 1: Tick on skin

Fig no 2: Tick on thumb

Fig no 3: Adult Female Deer Tick

Fig no 4: Different types of Ticks

Fig no 5: Early Signs and Symptoms

EARLY LOCALIZED INFECTION:

Early localized infection can occur when the infection has not yet spread throughout the body. The classic sign of early localized infection is circular rash called erythema chromium migrans, which occur at the site of tick bite 3 to 32 days after tick bite. The rash is red and may be worm, but is generally painless. Affected individuals can also experience flu -like symptoms, such as headache, muscle soreness, fever and myalgia.

EARLY DISSEMINATED INFECTION:

Within days to weeks after the onset of local infection, the borrelia may begin to spread through the blood stream. Borrelia^5-8 lymphocytoma a purplish lump that develops on the ear lobe, nipple, and various acuteneurological problems termed as neuro borreliosis, appear in 10-15% of untreated patients. these includes facial plasy which is the loss of muscle tone, on one or both sides of face, as well as meningitis, neck stiffness and sensitivity to light, inflammation of spinal cords, nerve roots can cause shooting pains that may interfere with sleep, as well as abnormal skin sensations. Mild encephalitis may lead to memory loss, sleep disturbances. Some case reports have described altered mental status as the only symptom seen in a few case of early neuroborrelion’s. This disease may adversely impact the heart’s electrical conduction system and can cause abnormal heart rhythms such as atrio ventricular blocks.

LATE DISSIMINATED INFECTION:

The late dissiminated stage is where the infection has fully spread throughout the body. After several months, untreated or inadequately treated patients may go on to severe and chronic symptoms that effect many parts of the body, including brain, nerves, eyes, joints and heart. Many disabling symptoms can occur including permanent impairment of motor or sensory function of lower extremities in extreme cases. A polyneuopathy that involves shooting pains numbness, and tithing in the hands or feet may develop. chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, brain fog, migraines, balance issues, weakness in legs, awkward gait, facial plasy, bladder problems, and back pain, in rare cases untreated lyme disease may cause frank psychosis which may be mis –diagnosed a schizophrenia or bipolar disorder. Panic attacks and anxiety can occur delusional behavior may be seen including somatoform delusions, sometimes accompanied by depersonalization or derealization syndrome, where the patients begin to feel detached from themselves or reality. Lyme arthritis usually affects the knees. In minority of patients, arthritis can occur in other joints including the ankles, elbows, hips and shoulders. Pain is often mild or moderate usually with swelling at the involved joints. Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe among the elderly. ACA begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.

HOW LYME DISEASE IS TRANSMITED:

Lyme disease is classified as a zoonosis as it is transmitted to humans from birds, and small mammals. The main vector of Lyme disease is a hard bodied tick of genus lxodes .the nymphal stage of tick’s causes infections, since they are small and thus live long periods of time in the human body as the tick bites often go unnoticed. Tick secretions prevent the host from felling itch or pain from bite. Transmission across the placenta during pregnancy is a pattern of congenital Lyme borreliosis. adverse pregnancy outcomes are possible with untreated infection. Lyme spirochete DNA has been found in semen and breast milk. Ticks that transmit B.burdoferi to humans can also carry and transmit several other parasites, such as theileria microtic and anaplasma phagocytophilum, which cause the disease babesiosis and human granulocytic anaplasmosis.

PATHOPHYSIOLOGY:

B. burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system. Many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues. Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. This provides a protective environment where the spirochete can establish infection. Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of the disseminated disease.

The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete. In the brain, B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis), which may contribute to neurodysfunction.

The spirochetes may also induce host cells to secrete quinolinic acid, which stimulates the NMDA receptor on nerve cells, which may account for the fatigue and malaise observed with Lyme encephalopathy. Tryptophon a precursor to serotonin appears to be reduced within the central nervous system in a number of infectious diseases that affect the brain, including Lyme.

HOW TO TREAT LYME DISEASE:

Antibiotics are the primary treatment. The specific approach to their use is dependent on the individuals affected and stage of the disease. For most people with early localized infection oral administration of doxycycline is widely used as a first choice, as doxycycline is contraindicated in children younger than eight years of age and women who are pregnant, breast feeding. alternatives to doxycycline are amoxicillin, ceftriaxime, cefriaxone, peniciliin and erthromycin,. Intravenous administration of cefriaxone is recommended as the first choice in early disseminated or late infected people.

COMPOSITION OF DOXYCYCLINE:

It is used as tetracycline. The active substances is doxycycline hycrate.The other ingredients in the capsule are sucrose, maize starch, crospovidone, basic butylated methacrylate copolymers and purified talc. The capsule shell containing gelatin and the coloring titanium dioxide, indigo carmine, red iron oxide.

COMPOSITION OF AMOXICILLIN:

It is used as antibiotic. The active substance of amoxicillin is amoxicillin trihydrate. The capsule also contains the following inactive ingredients: magnesium stearate, maize starch, gelatin, erythrosine, quinolinic yellow, titanium dioxide, red iron oxide.

COMPOSITION OF ERYTHROMYCIN:

It is used as antibiotic. The active substance is erythromycin. The other ingredients are maize starch, croscarmellose sodium type A, povidone, talc, magnesium stearate hypromellose, macrogol 6000, erythrosine, methacrylic acid, ethylacrylate copolymer and polysorbate 80.

COMPOSITION OF CEFUROXIME:

It is used as antibiotic. The active substances are cefuroxime. The other ingredients are microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulphate, colloidal anhydrous silica, calcium stearate, calcium carbonate and crospovidone. The tablet coating contains hypromellose and propylene glycol and the coloring agent titanium dioxide.

HOW TO PREVENT LYME DISEASE:

· The best way to prevent Lyme disease is avoid areas where deer ticks live especially wooded, bushy areas with long grass. We can decrease our rate of risk with simple precautions.

· COVER UP:- when in wooded or grassy areas, wear shoes, long paints tucked into your scoks, along sleeved shirt, a hat and gloves.

· Work clothing used in risky areas should be washed in hot water and dried in a hot dryer to kill any ticks.

· Light colored clothing is preferred because light colored make the tick more visible before it attaches.

Use Insect Repellents:

Apply insect repellent with a 20 percent or higher concentration of DEET to your skin. Apply product with premethrin to clothing or buy pretreated clothing.

· People who work in areas with wood, bushes, leaf litter, and tall grass are at risk of becoming infected with Lyme, so they need to take special care.

· Knowledge about Lyme disease transmission and infection risks should be known to people, so this can be done by educating the people about how to check themselves for ticks on the armpits and hair.

Check Yourself You’re Children And Your Pests For Ticks:

Be especially vigilant after spending time in wooded or grassy areas, deer ticks are often and no bigger than the head of a pin, so you may not discover them unless you search carefully.

It’s helpful to shower as soon as you come indoors. Ticks often remain on your skin for six hours before attracting themselves.

VACCINATION:

A recombinant vaccine against Lyme disease based on the outer surface protein A and B burgdorferi. New vaccines are being researched using outer surface protein and glycoprotein as methods of immunization. Vaccines have been formulated and approved for prevention of Lyme disease. The vaccine used for Lyme disease is Lyme wax.

VACCINE EFFECTIVE:

Lymerix was compared with placebo in a endemic area in 1936, healthy individuals who were given three doses of the vaccine. After the third dose was administered at 12months, Lyme disease was diagnosed in 16 vaccine recipients and 66 placebo recipients giving a vaccine efficiency of 76%.

VACCINE SAFE:

Lymerix recipients had more frequent reports at the infection sites than the placebo recipients of soreness. Adverse events usually were reported in the first 48 hours after immunization. Vaccine should only be considered as an adjunctive measure to avoid Lyme disease. Personal control measures such as avoiding tick infected areas, covering exposed skin ,wearing light colored clothes to allow easier observation and removal of ticks, examination for ticks each evening and tick repellents are all important measures in preventing Lyme disease.

DOSAGE AND ADMINISTRARTION:

First immunization against Lyme disease consists of 0.5 ml dose of Lymerix given at 0, 1, and 12 months. Vaccination with all three doses is required to achieve optimal protection.

STORAGE:

Storage between 2 ºC to 8 ºC, do not freeze, discard if product has been frozen

TICK REMOVAL:

Attached ticks should be removed promptly as removal within 36 hours can reduce transmission rates. The best method is simply to pull the tick out with tweezers as close to the skin as possible, without twisting, and avoiding crushing the body of the tick or removing the head from the tick’s body. The risk of infection increases with the time the tick is attached and if a tick is attached for fewer 24 hours.

Fig no 6: Tick removal by tweezer

PREVENTIVE ANTIBIOTIC:

The risk of infectious transmission increases with the duration of tick attachment .it requires between 36 to 48 hours of attachment for the bacteria that cause Lyme to travel from within the tick in to the saliva. If the deer tick that is sufficiently likely to be carrying borrelia is found attached to a person and removed , and if the tick has been attached for 36 hours, a single dose of doxycycline administered within the 72 hours after removal reduce the risk of Lyme diseases.

IMMUNOLOGICAL STUDIES OF LYME DISEASE:

Exposure to the Borrelia¹⁰ bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response; a form of pathogen-induced autoimmune disease. The production of this reaction might be due to a form of molecular mimicry, where Borrelia avoids being killed by the immune system by resembling normal parts of the body's tissues. Chronic symptoms from an autoimmune reaction could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy; similar to rheumatic fever, but its wider application is controversial

HOW TO DIAGNOSIS LYME DISEASE:

Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as facial piasy or arthritis) or a history of exposure to infected ticks, as well as serological blood tests. Diagnosis of rate-stage Lyme disease is often complicated by a multifaceted apprence and non specific symptoms, prompting one receiver to call Lyme the new “great imitator”

CONCLUSION:

Currently, the most scientific and effective way to address the issue of Lyme or Lyme-like illness being caused by agents that have yet to be identified is to focus on the prevention of all tick-borne diseases. DHSS believes that increased awareness of all tick-borne diseases in the state is critical to our citizens who depend on the outdoors for their livelihood and recreation. DHSS has begun to address this need by promoting personal protection and prevention – the use of insect repellants containing an active ingredient that repels or kills ticks and the practice of frequent tick-checks when working or recreating in tick habitat. Educational tools include paid radio announcements, billboards, posters, as well as tick-borne disease training for local public health agencies. Finally, a CDC-sponsored clinical study⁸ is available to physicians.

ACKNOWLEDGEMENT:

The authors are grateful to the authorities of Vishnu Institute of Pharmaceutical Education And Research, Vishnupur, Narsapur, and Medak for the facilities.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

1. Allen C, Steere, Jenifer Coburn, Lisa Glickstein, “The emergence of Lyme disease” J Clin Invest. 2004 Apr 15; 113(8): Pages 1093- 1101.

2. Mead PS, “Epidemiology of Lyme disease” Infect Dis Clin North Am. 2015 Jun; 29(2): Pages 187-210.

3. Priem S, Burmester GR, Kamradt T, Wolbart K, Rittig MG, Krause A. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Ann Rheum Dis. 1998;57:118–121.

4. S.K.Singh, H.J.Girschick, “Lyme borreliosis: from infection to autoimmunity”, Clinical Microbiology and Infection, Volume 10, Issue 7, July 2004, Pages 598-614.

5. Hermann J Girschick, Henner Morbach, Dennis Tappe “Treatment of Lyme borreliosis” Arthritis Res Ther. 2009; 11(6): 258.

6. Hengge UR, Tannapfel A, Tyring SK, Erbel R, Arendt G, Ruzicka T. Lyme borreliosis. Lancet Infect Dis. 2003; 3:489–500.

7. Maraspin V, Ruzic-Sabljic E, Strle F. Lyme borreliosis and Borrelia spielmanii. Emerg Infect Dis. 2006; 12:1177.

8. Herzberger P, Siegel C, Skerka C, Fingerle V, Schulte-Spechtel U, van Dam A, Wilske B, Brade V, Zipfel PF, Wallich R, Kraiczy P. Human pathogenic Borrelia spielmanii sp. nov. resists complement-mediated killing by direct binding of immune regulators factor H and factor H-like protein 1. Infect Immun. 2007; 75:4817–4825.

9. Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med. 1996;335:1270–1274.

10. Huppertz HI, Bohme M, Standaert SM, Karch H, Plotkin SA. Incidence of Lyme borreliosis in the Wurzburg region of Germany. Eur J Clin Microbiol Infect Dis. 1999;18:697–703.

Received on 22.01.2018 Modified on 18.02.2018

Res. J. Pharma. Dosage Forms and Tech.2018; 10(1): 17-22.

DOI: 10.5958/0975-4377.2018.00004.6

SYSTEM	STAGE 1 (EARLY) LOCALIZED	STAGE 2 (EARLY) DISSEMINATED	STAGE 3 (LATE) CHRONIC
Skin	Erythema migrans	Secondary annular lesions
Musculoskeletal	Myalgia, arthralgia	Migratory pain in joints; brief arthritis attacks	prolonged arthritis attacks, chronic arthritis
Neurologic	Headache	Meningitis, Bell palsy, cranial neuritis, radiculoneuritis	Encephalopathy, polyneuroathy, leukkoencephalitis
Cardiac		Atrioventricular block, myopericarditis, pncarditis
Constititional	Flulike symptoms	Malaise, fatigue	Fatigue
Lymphatic	Regional lymphadenopathy	Regional or generalized lymphadenopathy