GREENWICH DEPARTMENT OF HEALTH

Transcription

1 GREENWICH DEPARTMENT OF HEALTH LYME AND OTHER TICK ASSOCIATED DISEASES According to the literature, there are over 10 recognized human diseases associated with ticks in the United States today. Although for many years Rocky Mountain Spotted Fever (RMSF) was considered the major tick-associated disease in the country, Lyme disease (LD) is now in the forefront with over 23,700 human cases reported in Among the states reporting Lyme disease in 2002, the State of Connecticut ranked second overall nationwide, with 4,631 human cases. In addition, Connecticut was one of twelve states that registered the majority (95%) of the reported cases including incidence rates higher than the national average. Like other tick-associated diseases in the U.S., Lyme disease is greatly underreported with only 10-20% of the diagnosed physician cases being reflected in the total number. In the year 2003, the State of Connecticut eliminated the laboratory reporting requirements for Lyme disease and therefore, only reported 1,403 human cases. Unfortunately, this reporting change presents a false disease incidence rate, which should indicate an increase rather than a decline. According to several surveys conducted, approximately 25% of the residents living in Lyme disease endemic areas have been diagnosed with the disease. Although most people surveyed perceive Lyme disease and other tick-associated diseases as serious, less than half take necessary precautions to protect themselves. In the northeastern part of the U.S., three tick-associated diseases (Lyme disease, human ehrlichiosis and human babesiosis) get the greatest attention. Although each disease can be transmitted to humans by an infected tick bite, only one (human babesiosis) is not exclusive of this method. In an effort to stress the importance about the risk of human illness associated with these diseases, the following information has been selectively gathered from various publications. The intent of this literature is not to cover all of the known facts, but rather to provide necessary information for protection against disease. 1

2 The following topic discussions will include: disease information and transmission, personal protection measures, tools to manage tick populations on residential properties and instructions for tick removal and testing. A list of contact resources and pertinent websites has also been included for further reference. UNDERSTANDING DISEASE TRANSMISSION To understand the risk of acquiring a tick-associated disease, a general overview describing ticks will be needed. Increasingly, ticks have become a problem for humans and animals in the United States. They are considered obligate blood-feeders that require a host animal to survive and reproduce. Although ticks are capable of transmitting pathogens associated with human and animal disease, not all of them become infected. There are about 80 species of ticks in the United States; however only 15% of that total are of public health or veterinary concern. Ticks have four stages in their life cycle (egg, the 6-legged larva, the 8-legged nymph and the adult male or female) and cannot fly or jump. They are specific when it comes to their feeding habits (feed on humans, animals or both) so when searching out a needed blood meal, ticks must make direct contact with a host. As in many tick-associated diseases, the causative agent (which includes viruses, bacteria, rickettsiae and protozoa) is transmitted to humans by the tick. For example, Lyme disease (LD) is caused by the spirochete Borrelia burgdorferi, a corkscrew-shaped bacterium. It is passed on to humans through the bite of an infected black-legged tick (Ixodes scapularis) commonly known as the deer tick. Black-legged ticks are found in many areas throughout the nation, however, only a few Ixodes scapularis ticks in the southeastern part of the country have been found infected with the bacterium that causes Lyme disease. In contrast, in the northeastern part of the U. S. this Ixodes tick is responsible for transmitting Lyme disease as well as the causative agents of two additional diseases, human babesiosis and human ehrlichiosis. Tick Life Cycle: larva, nymph, adult male & adult female STAGE 1: Larvae STAGE 2: Nymph Host- white footed mouse, birds or other small animals Host - white footed mouse, bird or other small animals STAGE 3: Adults (male and female) Host - white tailed deer STAGE 4: Egg (Adult female tick dies after laying eggs) Most ticks, including Ixodes ticks, have a 3-host life cycle, whereas each of the active life stages feed on a different host animal for nourishment (blood meal). The immature stages of the tick, larvae and nymphs, generally feed on small to medium sized host animals (mice, chipmunks, birds, etc.) while adult ticks (90%) feed on larger animals such as a deer. Although ticks feed on the host ani- 2

3 mal for only a few days, the tick spends most of the time in the environment seeking another host. In addition, ticks use odor attraction (carbon dioxide, lactic acid, etc.) to detect their hosts. The black-legged tick, Ixodes scapularis (the deer tick), feeds from 3 to 7 days on a wide variety of mammals and birds. The larval and nymph stage of this tick typically become infected with Borrelia burgdorferi (bacterium that causes Lyme disease) when they feed on one of these host animals that carries the bacterium. The white-footed mouse is the principal host reservoir (source of infection) for Borrelia burgdorferi, along with Babesia microti (a protozoan agent that causes human babesiosis) and Anaplasma phagocytophilam, the bacterium that causes human granulocytic ehrlichiosis. In a study where white-footed mice were tested for the presence of all three causative agents, almost half of them were found to carry them. In addition over 90% of the mice were positive for the Borrelia bacterium. Birds are also considered a major host for the immature stages of the tick and have been implicated in long-distance dispersal of Borrelia burgdorferi. White-tailed deer are the principal host for adult stage ticks; however, they are not the host reservoir (source of infection) for this bacterium. In northern states the Ixodes scapularis tick maintains the Lyme disease bacterium through a two-year life cycle. Although this explains why more adult ticks than nymphs get infected with Borrelia burgdorferi (two opportunities to become infected, once as a larva and once as a nymph), nymphs pose a higher risk for passing on the Borrelia bacterium because of their size (as small as a pin head). Two-Year Life Cycle for I. scapularis Deer Tick 3

4 In final review, there are potentially 7 months out of the year that personal protection against tick-associated diseases should be applied. However, the following months are most important, due to tick abundance: April, May, June, July, August, September and November. Life Cycle: Height of Activity for I. scapularis Deer Tick Larvae Nymph Adult July Sept May August Mar May Oct Dec Height of Activity: AUGUST MAY, JUNE, JULY APRIL NOVEMBER Note: Episodes of warm days during the year will promote hatches HUMAN BABESIOSIS Human babesiosis is a malaria-like illness that is caused by the parasite Babesia microti. White-footed mice, as well as chipmunks, voles and shrews are the principal reservoir (source of infection) for Babesia microti. The infected black-legged tick Ixodes scapularis transmits this parasite to humans. Human babesiosis has been recognized since the early 1970s in several states including Rhode Island, parts of Massachusetts and New York. The first Connecticut case of human babesiosis was reported in Recently evidence indicates that the organism is becoming widely distributed in the state as the number of diagnosed cases increases. Most human cases of babesiosis occur during the summer months (May -August) when nymphs of the black-legged tick are active. While adult blacklegged ticks can transmit the parasite, Babesia can also be transmitted through blood transfusions from asymptomatic donors. It is estimated that 36 hours or more is needed to transmit Babesia microti from an attached tick. In most patients where treatment is needed, antibiotics and other medications can be applied effectively. Signs and Symptoms Infection caused by Babesia microti is often accompanied by no symptoms or only mild flu-like symptoms in healthy individuals. The following is a list of possible signs and symptoms: Headache Fever Fatigue Chills Sweats Muscle pain (1-6 weeks after tick bite) Gastrointestinal symptoms Illness can be severe or fatal in the elderly, immunocompromised individuals and those with no spleen. 4

5 Highest incidence rate of severe disease in patients over 40 years of age. Fatalities have been reported in about 5% of the cases. A diagnosis of Babesia infection can be successfully made by serological and blood testing. Although babesiosis can be treated, immunocompromised individuals may harbor the parasite for months or possibly years following recovery. In some cases, relapse of disease in those individuals may also occur. Those who have had babesiosis should not donate blood. In some studies where Lyme disease patients have been evaluated, coinfection of two causative agents (Babesia microti and Borrelia burgdorferi) has been identified. When co-infection occurs, the patient often experiences overlapping clinical symptoms, a more severe illness and a longer recovery than either disease alone. HUMAN EHRLICHIOSIS Ehrlichiosis is a disease of both animals and humans which is caused by a group of bacteria with several genera and species. There are two principal forms of ehrlichiosis in humans, currently recognized in the United States human monocylic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE). The latter of the two types accounts for about two-thirds of all ehrlichiosis cases in the United States. Most cases of HGE have been reported from states where Lyme disease is highly endemic (CT and NY). The black-legged tick, Ixodes scapularis, the deer tick, is the principal vector in the northeastern states for HGE and the lone star tick, Amblyomma americanum, is the vector in southeastern regions. White-tailed deer are the reservoir host (source of infection) for the causal agent of HME, while white-footed mice and possibly deer are reservoirs for A. phagocytophilam, the bacterium that causes HGE. Most cases of HME and HGE occur during the summer in May, June or July, with 80-90% of cases occurring between April and September. It is estimated that the bacterium that causes HGE can be transmitted within 24 hours of tick attachment. A patient co-infected with B. burgdorferi and A. phagocytophilam (bacterium that causes HGE) can suffer more severe disease and experience a complication with the diagnosis of Lyme disease. In Connecticut there were 544 confirmed cases of HGE reported from Cases of HME in Connecticut are possible, as the causal agent has been detected in Lone Star Ticks. Signs and Symptoms The following is a list of signs and symptoms associated with HME and HGE: Fever Headache Muscle pain Nausea Vomiting Malaise Rash - Uncommon (in adults only) Illness may be mild, moderate or severe. Fatalities have occurred Highest incidence rate in patients over 50 years HME has been confused with Rocky Mountain Spotted Fever (RMSF) 5

6 A diagnosis of human ehrlichiosis should be considered for patients with flu-like illness and possible exposure to Ixodes scapularis, the black-legged tick. Confirmation of Ehrlichia infection can be obtained through serological and blood testing; however, tests may be negative in the early stages of disease. Ehrlichiosis in most patients with early disease can be treated with antibiotic therapy. LYME DISEASE Lyme disease (LD) is an illness that is caused by the spirochete Borrelia burgdorferi, a corkscrew-shaped bacterium. It is associated with the bite of an infected black-legged tick Ixodes scapularis, commonly known as the deer tick. Lyme disease was first recognized in Connecticut in 1975 when a group of young arthritis patients in Lyme, Connecticut were being studied. The emergence of Lyme disease is associated with the change in landscaping patterns (reforestation) and has become more prevalent with population increases of white-tailed deer and small animal hosts. Although deer are the principal hosts for the adult tick Ixodes scapularis, white-footed mice are the principal host reservoir (source of infection) for Borrelia burgdorferi. Other important hosts for the larval and nymphal stages of the tick include birds and small mammals such as chipmunks. Lyme disease is a multi-system disorder that exhibits many diverse signs and symptoms. Symptoms that occur within days or weeks of the infected tick bite reflect localized or early infection, while late manifestations of the disease can appear months or even years after infection. Although the major signs and symptoms of LD categorize the stages of infection, some patients do not experience all of them. In addition, in some individuals non-traditional symptoms occur. If Lyme disease is suspected, co-infection of Babesia microti (agent that causes human babesiosis) and the causative agents that cause human ehrlichiosis should be considered. It has been estimated that Borrelia burgdorferi can enter the bloodstream as early as 24 hours after tick attachment. It should be noted that only 14-32% of patients diagnosed with LD remember a tick bite. The following is a list of signs and symptoms that usually occur with different stages of Lyme disease. It should be noted that for some individuals, signs and symptoms may be different and/or absent. 6

7 Localized Infection Localized red rash (erythema migrams EM) occurs in 70-90% of patients: Typically appears within 9 days, but may take up to 30 days Gradually expands over time and varies in size and shape May occur anywhere on the body; commonly seen on the thigh, groin, trunk and axilla May be warm to the touch - usually not painful or itchy, but can be Bull s-eye appearance in less than one-half of the cases and usually resolves itself without treatment Mild non-specific systemic symptoms: In 80% of cases with rash Fatigue Muscle and joint pain Headache Fever Chills Sore throat Swollen glands Stiff neck Respiratory or possible gastrointestinal problems Others not mentioned above Early Disease Infection Borrelia bacteria are capable of masking themselves in the human body and deceiving the body s immune system. When the spirochete Borrelia burgdorferi makes its way into the body, it eventually goes into various organ systems, particularly the epidermal, muscular, nervous or cardiac tissue. The following are indications of early disease infection: Secondary rashes or hives may appear Days to weeks: migratory joint and muscle pain, panic attacks, malaise, fatigue, neurological (memory loss, concentration impairment, fogginess, speech impairment) or cardiac problems (chest pain, heart rhythm disturbances) may occur. Early neurological symptoms develop in 15% of untreated patients with paralysis of facial muscles (drooped eye and/or mouth), fever, stiff neck, pain in elbows and fingers, severe headache and arthritis in the knee (mostly in children) may occur. In about 8% of the patients, various degrees of cardiac problems occur. Ocular manifestations such as conjunctivitis may occur. Antibodies from the bacterium B. burgdorferi are usually detectable in tests during these manifestations; however, they can be absent despite infection. 7

8 Late Disease Infection A year or more after an infected tick bite, signs and symptoms of persistent infection will occur in untreated or inadequately treated individuals. The Borrelia bacterium can continue to proliferate in the body and even reach the brain. The following is a list of signs and symptoms that may occur in the late stages of infection: Numbness or tingling of extremities (fingers and toes) Sensory loss (smell, taste) Weakness and fatigue (tiredness) Diminished reflexes (includes balance and strength) Disturbances in memory (includes memory loss and loss of words) Mood and/or sleep problems (anxiety, depression) Noticeable cognitive dysfunction (appearing confused and bewildered) Intermittent chronic arthritis with knee pain and swelling; stiff neck and pain in the elbows and fingers, etc. Arthritis develops in 50-60% of untreated individuals with 10% of these developing chronic arthritis The severity of Lyme disease varies among patients. Major signs and symptoms can be displayed; however, if they are mild, they may go unrecognized or undiagnosed. Some individuals may also experience unusual signs and symptoms or may be asymptomatic (absent of illness). If untreated or under-treated, the disease can also become chronic and debilitating. Although fatalities associated with LD occur rarely, if at all, individuals that do develop severe neurological manifestations can be left dysfunctional in some way. Those who are stricken with mild to chronic arthritis may not be relieved after treatment. Treatment of Lyme disease varies according to the stage of the disease, as well as among patients. Although, there is still a debate within the medical community about whether or not there is a chronic stage of this disease, patients do, in fact, go on to suffer more severe complications after being misdiagnosed, under-diagnosed or under-treated. The treatment of Lyme disease should be based upon the entire clinical picture of the patient, since there are no definitive test(s) that are capable of ruling in or ruling out infection with Borrelia burgdorferi. Since studies of Lyme disease patients indicate co-infection is possible with multiple tick-borne pathogens, testing for Babesia and Ehrlichia should also be considered. When concurrent infections with causative agents do occur, the patient may experience a change in signs and symptoms, the reliability of standard diagnostic tests and the persistent forms of each of the infections. Treatment of early disease infections in most patients can be successful with oral antibiotic therapy. However, it has been shown that patients with extended illnesses must be treated longer and more aggressively using oral and/or intravenous antibiotic therapy. If treatment is discontinued before all symptoms of active infection have cleared, illness will persist and relapse will most likely occur. Generally, early disease infection is treated for 4 to 6 weeks, while late disease 8

9 infection requires extended treatment (4 to 6 months or more). Because all patients respond differently to treatment, therapy must be individualized. The choice of medication used and the dosage prescribed will vary for different people. The use of combination therapy, which utilizes several antibiotics simultaneously and/or the use of other medications that have been found to work favorably are selected for the patient by the treating physician. Whatever the course of treatment, patients are advised to follow their physician s instructions carefully, including obtaining proper rest. Remember, currently there is no test to measure the cure; so clinical follow-up is paramount in Lyme disease care. Personal Protection Measures In an effort to limit the risk of enduring a tick-associated disease, personal protection measures must be implemented. The following is a list of personal protection measures when exposing yourself to infested tick habitat areas: Wear light colored clothing to spot ticks readily. Wear long sleeved shirts and pants when possible. Tuck pant tops into socks or boot tops. Wear outerwear such as windbreakers to reduce the likelihood of ticks grabbing on. Apply tick repellents containing permethrin onto clothing only. Apply insect repellents containing DEET concentrations to exposed skin by carefully following the manufacturers instructions. Never apply any repellent over wide areas of the body. Apply no more than 40% DEET concentration for adults, 10% for children and NEVER apply a repellent to an infant. Never apply DEET to the face. Place clothing that has had contact with a tick habitat in a dryer set on high for 20 minutes. Check all pets that frequent outdoors and apply a monthly tick treatment application as recommended by veterinarians. Ticks brought indoors may survive depending on humidity. Perform a tick check while still outdoors and at home. Promptly remove attached ticks. These steps are the most important and effective method of preventing infections. 9

10 Tick Removal and Testing Procedure The probability of transmission of Lyme disease spirochetes and other tick-associated causative agents increases with the length of time an infected tick is attached. The following steps should be carried out when removing a tick from the skin surface: 1. Use a fine-point, thin tipped tweezers to grasp the tick at the place of attachment, as close to the skin as possible. 2. Gently pull the tick straight out (upward) steadily. Note: The use of petroleum jelly or heat from a match is not effective and should not be used. 3. Place tick in a small sealable plastic bag for testing. 4. Note the date, time and place you found the tick. 5. After removing the tick, wash your hands thoroughly, disinfect the tweezers and clean the tick bite site with alcohol or other skin disinfectant. 6. Contact the Greenwich Department of Health Laboratory at for further instruction regarding tick testing services that analyze for the presence of Lyme spirochetes. All ticks dead or alive can be tested. 7. If signs and symptoms of Lyme disease appear, contact your primary physician immediately. Measures To Reduce Tick Habitats The majority (75%) of Lyme disease cases are associated with activities around the home. Children between the ages of 5-13 years of age are particularly at risk for tick bites because of playing outdoors. Although adult ticks have the best chance of carrying the bacterium that causes the disease, ticks in the nymphal stage pose the greatest risk to humans because of their size (about the size of a pin head). To increase protection against tick borne diseases, tick habitats must be reduced. Studies have indicated that tick populations can be reduced by 50% through a combination of practical landscaping changes. The following strategies can reduce tick abundance around your home. 10

11 The tiny nymphal deer tick, which feeds in the spring and summer, likes floor leaf litter and stonewalls. Remove these along with wood piles and birdfeeders, as they attract tick carrying small animals such as mice. Nearly 70 percent of ticks on residential lawns are found within nine feet of the woods edge. Keep lawns short and increase areas with sunshine when possible. Eliminate moist, shady environments around your home by pruning overgrown shrubs and trees. Ticks like damp underground areas so eliminate ground cover plants such as pachysandra near walkways and play areas. Consider planting deer resistant plants and shrubs such as barberry, needle-bearing evergreens, forsythia, bee balm, foxglove and ornamental grasses. Since deer like to eat flowering plants, it is suggested that they are kept away from the house and play areas. Suggestions on other plantings may be available through local nurseries. Create a barrier between the wooded areas and your lawn. See Safe Tick Zone for more information. Provide screening under porches and decks so that mice, chipmunks and other small mammals cannot nest. Note: mice and chipmunks nest in stone walls, tree cavities and under logs. Although they only have 3 to 4 young in their litter, they breed in the spring through the fall every 25 days. Consider deer fencing to control nuisance deer where practicable. Studies indicate that deer fencing does not significantly reduce the tick population unless the fence surrounds an area of acres or more. When using deer fencing be sure to use the proper type. Creating A Tick Safe Zone to Reduce Tick Survival All ticks require moist and humid conditions to survive. Ticks are most abundant in areas where there is indirect sunlight, ample leaf litter and dense vegetation. Although ticks may be found on grassy areas, they do not survive well in areas exposed to prolonged direct sunlight. Ticks that are found on lawns are usually within 9 feet of the edge of wooded areas. Create a Tick Safe Zone on your property. This is an area that has been designed to reduce the number of ticks near and around your home. The safety areas should include areas that are used by the family, such as recreational sites, walkways and gardens. They should be well maintained during times when ticks are active (April - September) and other times when warm weather conditions continue. The protected area should always have a lot of sun. The following is a list of measures to take when creating a Tick Safe Zone: 11

12 Creating A Tick Safe Zone to Reduce Tick Survival Establish your safe area no less than nine feet from the edge of the woods. Locate mailboxes, sheds, picnic tables, recreational areas and play equipment areas in the sun. 12

13 Chemical: Trim tree branches back from the safe zone. Clear away brush, weeds and leaf litter from walkways. Restrict groundcover plants to areas of the yard that are not used by the family. Use materials such as woodchips or gravel in shady areas within your safe zone. Always keep your grassy lawn cut short. Create a woodchip, mulch or gravel barrier where your lawn meets the woods. The barrier should always be at least three feet wide. Other Methods for Tick Control The decision to use a chemical to control ticks on private property is strictly individual. A chemical that kills ticks is called an Acaricide. Many of the products are restricted for use to certified commercial applicators. These pesticides or insecticides may be applied to lawns and woodland edges to kill ticks around the home. Acaricides are applied once or twice a year to control nymphs and adult ticks. Using a chemical can pose a danger to health and the environment so choosing the right pesticide and applying it correctly is essential to safety and effectiveness. Always hire a State of CT licensed professional applicator when applying a pesticide to control ticks. Always consider an organic or synthetic product in the chemical class called pyrethrums. Pyrethrins are natural toxins produced from certain species of chrysanthemum flowers; pyrethroids tend to be more effective synthetic derivatives. Because some of these products break down rapidly, multiple applications may be required. A single application of most ornamental-type insecticides will provide 85-90% control with some residual activity so additional applications are rarely necessary. Apply at the edge of your tick safe zone in mid-may or early June to reduce the nymphal tick population. When using pesticides, treat only the tick habitat (including ground cover vegetation) and always follow the manufacturer s guidelines for safe treatment. Never discontinue personal protective measures. Spraying of open fields and lawns is not necessary when using chemicals to control ticks. Never spray vegetable, herb or butterfly gardens. Always store chemicals away from children and pets. 13

14 In 2003, the Environmental Protection Agency (EPA) approved Maxforce a tick management system which is available through licensed pesticide applicators. This system utilizes bait boxes for topical treatment of rodents with a product called fipronil. Bait boxes contain non-toxic food blocks, are ready to use and are child resistant. This method has been found effective after the second year of implementation. Some acaricides (pesticides) used for the control of ticks in the residential landscape: Carbaryl Sevin Other brands Cyfluthrin Tempo Powerforce Permethrin Astro Ortho Products Others A carbamate insecticide. May be used against ticks on turf and recreational areas. Numerous brands available for public use and commercial use where indicated. Sprays and granules reported effective against ticks. A pyrethroid insecticide. May be used against ticks on turf and ornamentals. Available for commercial and homeowner use with concentrates. Effective against black-legged ticks. A pyrethroid insecticide. There are concentrates and ready-to-spray products. Most are for homeowner use, few are for commercial use only. Bifenthrin Talstar Ortho Products A pyrethroid insecticide. Available in liquid and granular form for homeowner use. Also available for commercial applicators. Non-Chemical: Due to concerns about synthetic pesticides, industry is attempting to develop alternative methods to control ticks and other insects. Certain soaps and salts of fatty acids have been known to kill insects; however, the efficiency of these products alone to control ticks is unproven at this time. 14

15 Conclusion: Lyme disease is endemic in the State of Connecticut. Other tick-associated diseases such as human babesiosis and human ehrlichiosis are becoming equally as important, since more than one bacterial infection can develop from a single infected tick bite. Although persons of all ages are considered susceptible, the highest reported incidence is in children less than 15 years of age and adults 30 to 59 years of age. Because suppression and control of tick-associated diseases have been largely unsuccessful, the principal means of prevention remain personal protection measures. Wearing protective clothing, applying repellents, avoiding tick infested areas and promptly removing ticks on skin and clothing will reduce the risk of disease exposure. Early detection and prompt treatment by physicians who specialize in tick borne diseases, will help to reduce serious manifestations of disease after exposure. Finally, there is no available vaccine for the treatment of tick-borne diseases in the United States. The enormous costs associated with developing and evaluating vaccines that have only a limited market will more than likely preclude the commercial manufacture of new vaccines in the near future. Therefore, based upon the foregoing, it is imperative to prevent tick bites. 15

16 REFERENCES AND WEBSITES OF INTEREST Greenwich Department of Health Division of Environmental Services (203) Laboratory M-F 8:00 AM 3:00 PM (203) Website: Stafford, Kirby Tick Management Handbook, Connecticut Agricultural Experiment Station, New Haven, CT Centers for Disease Control and Prevention (CDC) National Institutes of Health National Pesticide Information Center Pesticide-related Fact Sheets Environmental Protection Agency Citizen Guide to Pest Control and Tips on Hiring a Pesticide Applicator American College of Physicians American Lyme Disease Foundation, Inc. Connecticut Department of Public Health Time For Lyme, Inc. Lyme Disease Association, Inc Not responsible for typographical errors.