MALARIA

Malaria is caused by infection with one of four microscopic protozoan parasites: Plasmodium falciparum, P. vivax, P. malariae, or P. ovale. These are transmitted in the wild by the bite of an infected Anopheles mosquito. Of the nearly 430 species of Anopheles mosquitoes, only 30 to 40 transmit malaria. Most cases of malaria acquired by U.S. citizens are contracted in sub-Saharan Africa; most of the remainder are linked to travel in Southeast Asia, Central and South America, the Indian subcontinent, the Middle East, and Oceania (Papua New Guinea, Vanuatu, and the Solomon Islands).

Mosquitoes bite humans to obtain a blood meal in order to produce eggs. When a female mosquito bites a human infected with malaria, it ingests an immature form of the parasite. In approximately 2 weeks, the parasite matures within the mosquito. When the infected mosquito bites a noninfected human, it releases malaria sporozoites (an immature form of the parasite), which mature in the human liver to become merozoites, and which then invade red blood cells. From these locations, the organisms can penetrate the vital organs, such as the brain, lungs, liver, and kidneys. Within a few days, the infected red blood cells burst and the parasites infect more red blood cells. The incubation period between acquisition of the parasites and the onset of symptoms is 8 to 40 days, depending on the species. Up to a third of victims may not show the disease until after 60 days from the time of the initial mosquito bite. Typical symptoms include a flu-like illness, with any or all of the following: headache, chills, sweats, fatigue, backache, pale skin, loss of appetite, muscle aches, nausea, diarrhea, and vomiting. These are soon followed by episodes of headache, intense chills (rigors), high fever, and sweating. Jaundice and anemia may occur. The episodes last 1 to 8 hours and are separated by 2 to 3 days, depending on the species.

Those infected with falciparum malaria may be significantly more ill, with episodes of fever and chills at closer intervals and lasting for more than 30 hours. In addition, there may be severe alteration in mental status, seizures, difficulty breathing, blood in the urine, severe anemia, and shock. Severe malaria can be fatal or lead to anemia, heart and kidney failure, and/or coma; untreated infections can cause recurrent illness for years.

Identification of the specific plasmodium is accomplished by observing the parasites under the microscope in blood smears. People infected with P. falciparum are treated with quinine sulfate in combination with pyrimethamine-sulfadoxine (Fansidar) or tetracycline. The most important new class of antimalarial drugs is the artemisinins, which are natural products that were first developed in China in the 1960s. Artemether, artesunate, artemotil, and dihydroartemisinin (all artemisinin, or qinghaosu, derivatives) have been shown to be effective in the treatment of severe P. falciparum malaria. One key advantage of these agents is that they are active against all of the red blood cell stages of the parasite. Also, so far there is limited if any resistance to these agents. Because all artemisinins are very effective in killing the parasites, they are cleared rapidly from the bloodstream; so, are combined with longer-acting drugs, such as mefloquine, lumefantrine, amodiaquine, or piperaquine in countries other than the United States. At the time of this writing, in the United States, intravenous artemesinin is still considered an investigational drug, so it must be obtained from the Centers for Disease Control and Prevention (CDC). It is used for 3 days, and then followed with a longer-acting oral drug such as doxycycline, clindamycin, atovaquone-proguanil, or mefloquine. A person infected with P. vivax, P. malariae, or P. ovale is treated with chloroquine and primaquine phosphate.

Unfortunately, there is not yet a useful vaccine against malaria. Avoidance of mosquito bites is key to prevention. Because the Anopheles mosquito tends to feed during the evening and nighttime, it is particularly important to sleep under nets or screens; spray living quarters (with, for instance, a pyrethrin-containing product) and clothing (with, for example, permethrin 0.5%, Duranon, or Repel Permanone; or concentrated Perma-Kill 4 Week Tick Killer, diluted and applied to clothing); and wear adequate clothing and insect repellent (N,N-diethyl-3-methylbenzamide, called DEET) at these times (see page 390).

If you travel to a region where P. falciparum is resistant to chloroquine and pyrimethamine-sulfadoxine, prophylaxis (prevention) can be accomplished with mefloquine. The adult dose is 250 mg (salt) weekly. The pediatric dose varies according to the weight of the child: weight 15 to 19 kg, 63 mg; weight 20 to 30 kg, 125 mg; weight 31 to 45 kg, 188 mg; and over 45 kg, 250 mg. (For estimating purposes, 1 kg equals 2.2 lb.) Mefloquine should be started 1 to 2 weeks before travel, and then administered once a week during travel in malarious areas and for 4 weeks after you leave such areas. Mefloquine should not be taken during pregnancy. This drug should not be used by persons with psychiatric disease or history of depression or seizures. Side effects include nausea and vomiting, dizziness, mood changes, difficulty sleeping and nightmares, headache, and diarrhea.

An alternative drug for travelers who cannot take mefloquine is doxycycline (the adult dose is 100 mg a day beginning 1 to 2 days before travel and continuing for 5 to 6 weeks after; the pediatric dose for those aged more than 8 years is 2 mg/kg of body weight a day, up to the adult dose). Doxycycline is not advised for pregnant women or children under age 8 years, and may cause increased skin sensitivity to sunlight.

A final drug prophylaxis regimen against malaria is chloroquine phosphate (the adult dose is 300 mg of the base once a week; the pediatric dose, 5 mg/kg of the base, up to the adult dose, once a week), which should be taken 1 to 2 weeks before you enter a malarious region and continued until 1 month after your journey. Chloroquine is recommended for travelers, particularly pregnant women and children who weigh less than 33 lb (15 kg), who cannot take mefloquine or doxycycline. If you use chloroquine for prophylaxis, you should also carry three tablets of Fansidar to be taken in the event of a flu-like illness or other unexplained fever, assuming the absence of an allergy to sulfonamide antibiotics. Chloroquine should not be used by persons with retinal problems and has side effects of headache and itching.

Proguanil (Paludrine) is a drug that may be used for antimalarial prophylaxis in areas where P. falciparum is resistant to chloroquine. The drug is available without prescription in parts of Europe, Scandinavia, and Africa, but is as yet unavailable in the United States. It is administered in an adult dose of 200 mg daily (pediatric dose: under 2 years, 50 mg; age 2 to 6 years, 100 mg; age 7 to 10 years, 150 mg; over 10 years, 200 mg), along with weekly chloroquine (the latter to protect against other forms of malaria). It can be used by those who will spend more than 3 weeks in rural areas of East Africa (particularly Kenya and Tanzania), but does not appear to be useful in Papua New Guinea, West Africa, or Thailand.

Atovaquone in combination with proguanil hydrochloride is available as the drug Malarone. The drug is taken at the same time each day with food or a milky drink. Treatment should be started 2 days before entering a malaria-endemic area and continued for 7 days after return. The adult dose is one tablet (250 mg atovaquone/100 mg proguanil) per day. Each pediatric tablet of Malarone contains atovaquone 62.5 mg/proguanil 25 mg. The pediatric dose is based on weight: 11 to 20 kg, one pediatric tablet per day; 21 to 30 kg, 2 tablets; 31 to 40 kg, 3 tablets; greater than 40 kg, one adult tablet. It should be noted that if Malarone is taken with tetracycline, metoclopramide, rifampin, or rifabutin, it may be less bioavailable and thus potentially less effective. It should not be used by persons with significant kidney disease.

Pyrimethamine plus dapsone (drug combination: Maloprim) is prescribed in many malaria-endemic regions outside the United States. This drug cannot be used by pregnant women; it can also cause bone marrow suppression.

If you are stricken with malaria in an area where the malaria organism(s) is believed to be sensitive to chloroquine, but you have not been taking prophylaxis, begin treatment with chloroquine (adult dose, 600 mg of the base immediately, followed with 300 mg at 6 hours and once a day on days 2 and 3; pediatric dose, 10 mg/kg of body weight [up to 600 mg] of the base immediately, followed by 5 mg/kg at 6 hours and once a day on days 2 and 3). In a region where P. falciparum is resistant to chloroquine, administer quinine sulfate (adult dose, 650 mg every 8 hours for 3 days; pediatric dose, 8 mg/kg [up to 650 mg] every 8 hours for 3 days) plus tetracycline (adult dose, 250 mg four times a day for 7 days; pediatric dose, 5 mg/kg [up to 250 mg] four times a day for 7 days) or Fansidar (adult dose, 3 tablets; pediatric dose: weight 5 to 10 kg, ½ tablet; weight 11 to 20 kg, 1 tablet; weight 21 to 30 kg, 1 ½ tablets; weight 31 to 45 kg, 2 tablets; weight over 45 kg, 3 tablets). (For purposes of estimation, 1 kg equals 2.2 lb.) Malarone is sometimes used to treat acute malaria caused by P. falciparum. In this case the dosage for treatment is based on body weight: 5 to 8 kg, 2 pediatric tablets each day for 3 consecutive days; 9 to 10 kg, 3 pediatric tablets for 3 days; 11 to 20 kg, 1 adult tablet for 3 days; 21 to 30 kg, 2 adult tablets for 3 days; 31 to 40 kg, 3 adult tablets for 3 days; greater than 40 kg, 4 adult tablets for 3 days. Halofantrine (Halfan) is used to treat chloroquine-resistant P. falciparum infections in a dose of 500 mg every 6 hours for three doses, with repeat therapy in 7 days.

In any case of suspected malaria, seek the advice of a physician as soon as possible. Anticipate that a stricken individual, particularly a child, may develop extremely low blood glucose (sugar).

To determine the malaria risk within a specific country and to learn of the most recent recommendations for prophylaxis and drug therapy, you can seek information from one of many sources on the Internet, such as www.cdc.gov/malaria/.

YELLOW FEVER

Yellow fever is a viral disease transmitted in the jungle by mosquitoes of the genus Haemogogus and in urban areas by Aedes aegypti mosquitoes. “Jungle” yellow fever is seen in forest-savanna zones of tropical Africa, parts of Central America, forested areas of South America, and Trinidad. The “urban” variety is seen in South America and West Africa. The disease has not yet been noted in Asia.

The illness begins 3 to 6 days after the culprit mosquito bite(s). Symptoms include sudden onset of fever, headache, red eyes, muscle aching, nausea, and vomiting. These symptoms last for 3 to 4 days, after which there may be 12 to 24 hours of remission. Soon thereafter comes an “intoxication phase,” in which the seriously stricken victim develops fever, skin rashes, altered mental status, low blood pressure, and liver and kidney failure. In such cases, the victim becomes jaundiced (hence, “yellow” fever) and bleeds easily. The disease can be fatal. Treatment is supportive and based on symptoms. Because of the bleeding problems, do not use aspirin to control fever.

Since yellow fever is so difficult to treat, it is essential to use yellow fever vaccine and mosquito control measures (see page 390). A live-virus vaccine is available. A single injection induces immunity after 10 days that is adequate for 10 years (see page 453).

DENGUE FEVER

Dengue fever is a viral (flavivirus) disease transmitted by Aedes albopictus and female A. aegypti mosquitoes. It is estimated that 50 to 100 million people in more than 100 countries are infected each year with dengue viruses. There are four different types of dengue virus, and there is no cross-immunity, so a person may be stricken with dengue fever four times in his life. The most active feeding times for dengue vector mosquitoes is for a few hours after daybreak and in the afternoon for a few hours just after dark (dusk). As opposed to the night-feeding mosquitoes that transmit malaria, these species tend to be “urban,” may also feed during daylight hours (also indoors, in the shade, and during an overcast), and are known to bite below the waist. Dengue fever is seen chiefly in the Caribbean and South America, as well as other tropical and semitropical areas, such as Southeast Asia, Africa, and Mexico. In the United States, cases have been noted in Texas. The larvae flourish in artificial water containers (e.g., vases, tires), often in a domestic environment.

The incubation period following a mosquito bite is 2 to 8 days. The disease is self-limited (5 to 7 days) and characterized in older children and adults by a sudden onset of severe headache, sore throat, fatigue, cough, high fever (greater than 39°C or 102.2°F), chills, muscle aches, sore throat, reddened eyes, enlarged lymph nodes, nausea, bone and joint pain (“breakbone fever”), and a fine, red, itchy skin rash that typically appears simultaneously with the fever on the proximal arms, legs, and trunk (it spares the face, palms, and soles). It may then spread to the face, and farther out on the arms and legs, becoming slightly darker and more solid. Although the fever usually remits spontaneously, an occasional victim will relapse. Some victims have a cycle of a few days of fever, then 1 to 3 days without fever, then fever again. It is not uncommon to suffer central nervous system manifestations, such as irritability, depression, seizures, or severe altered mental status. Children under 1 year of age appear to be particularly vulnerable to especially severe forms of dengue virus infection, associated with severe bleeding problems (dengue hemorrhagic fever: nosebleed, bleeding gums, severe abdominal pain, bloody vomit, darkened stool, restlessness, weakness, etc.) and circulatory problems that can lead to extremely low blood pressure (shock—see page 60). When this occurs, the victim may develop a diffuse, dark purple, blotchy rash caused by bleeding into the skin.

Treatment is supportive and based on symptoms. Fever should be treated with acetaminophen, and not with aspirin. There is no vaccine available against dengue fever. Insect repellents (particularly those containing DEET; see page 390) are critical for prevention.

CHIKUNGUNYA DISEASE

Chikungunya disease is similar to dengue fever. It is indigenous to tropical Africa and Asia. Caused by transmission of an alphavirus from a bite from the mosquito Aedes aegypti or A. albopictus, Chikungunya disease carries an incubation period of 2 to 12 (usually 3 to 7) days, followed by fever, headache, pain on looking at the light, pain behind the eyes, sore throat, nausea, vomiting, and weakness. On days 1 to 3, there may appear a red rash, followed by muscle aches and painful joints with arthritis. The arthritis may last for months to years. Therapy is symptomatic. As with dengue, proper use of insect repellents is critical.

WEST NILE VIRAL DISEASE

West Nile (named from the West Nile province of Uganda) viral disease (West Nile virus: WNV) is caused by a flavivirus (such as those that cause St. Louis encephalitis, Japanese encephalitis, and Murray Valley encephalitis) carried predominantly by mosquitoes (Culex pipiens in the eastern United States, C. pipiens quinquefasciatus in the southern United States, and C. tarsalis in the western United States, Aedes, Anopheles, and many other species) and at least 160 species of birds, although it has been found in small mammals and to an alarming degree in horses. The mosquitoes become infected by feeding on birds and many animals (e.g., bats, horses, chipmunks, dogs, rabbits, reindeer, squirrels, and even alligators). It appears to be transmitted to humans by mosquito bite and has been presumed to have arrived in the United States from the Middle East. In rapid fashion, it appears to have spread across the United States. The four top species of wild birds affected by WNV are American crows, Western scrub-jays, yellow-billed magpies, and Steller’s jays. Mosquitoes bite the birds and thus acquire the virus. West Nile viral disease is endemic in Africa, the Middle East, and West Asia. The virus has been spread to the recipient of an organ transplant from an infected donor, from a pregnant mother to a fetus, by blood transfusion, and possibly through breast milk. Otherwise, it does not appear to spread from human to human. While much of the clinical WNV activity is noted in summer and autumn, it is certainly possible to acquire the disease in winter from the bite of an infected mosquito.

The incubation period after a bite from an infected mosquito until the onset of illness is 3 to 14 days. The victim usually suffers a flu-like illness lasting for 3 to 6 days, characterized by fever, headache, neck stiffness and pain, swollen lymph glands, muscle aches and weakness, loss of appetite, fatigue, diarrhea, vomiting, red bumpy rash (commonly on the chest, abdomen, and back), and aversion to light (sometimes interpreted by victims as eye “pain”). Fatigue may be a residual symptom for up to a month. In 1 in every 100 to 300 cases, the victim suffers severe encephalitis (inflammation of the brain) with stiff neck and severe altered mental status (including coma or double vision), as well as paralysis. Convulsions are rare. Elders are more prone to suffer severe or fatal illness. Death is uncommon.

Most (80%) people infected with WNV never realize that they have had the disease, because they remain without symptoms. Twenty percent of infected people develop West Nile fever, and less than 1% of people infected develop severe medical illness, including meningitis and/or encephalitis (characterized by seizures, loss of vision, and disorientation) or paralysis. There are blood tests for WNV that measure antibodies to the virus, and show positive in most infected people within 8 days of the onset of symptoms. However, they may initially be “negative” and need to be repeated at a later date. There is no specific treatment, other than supportive therapy. Recovery is generally complete for survivors, although persistent neuropsychological problems (fatigue, memory problems, weakness, tremor, word-finding difficulties, headaches, and depression) may occur, even if the acute disease was mild.

Prevention is essential. First and foremost, that means preventing mosquito bites. Here are some recommendations:

RELAPSING FEVER

The sporadic (in occurrence) form of relapsing fever is caused by various borrelial organisms transmitted by argasid (soft) ticks of multiple Ornithodoros species. For instance, tick-borne relapsing fever in the western United States and Canada is caused by Borrelia hermsii, transmitted by the Ornithodoros hermsii tick. The epidemic form of relapsing fever is transmitted by the human body louse. In the United States, relapsing fever is largely confined to the western portion of the country, where the ticks inhabit coniferous forests in the remains of dead trees and burrows occupied by mice, rats, and chipmunks.

The disease is more common in men, who may occupy the poorly maintained cabins and huts that rodents like to visit. The classic case involves a tick bite and a 7-day incubation period, followed by the abrupt onset of high fever, shaking chills, severe headache, muscle and joint aches, abdominal pain, nausea, and vomiting. This lasts for about 3 (but may be 1 to 17) days, until there is a crisis wherein the fever drops while the victim undergoes drenching sweats and intense thirst. For a subsequent period that averages 7 days, there is no fever and minimal symptoms, and then a relapse into illness. This cycle recurs an average of three times, with each episode of illness generally less severe. The sporadic (tick-borne) variation tends to be less severe; mortality rates of up to 40% have occurred in louse-borne epidemics.

A physician can make the diagnosis by examining a smear of the victim’s blood under the lens of a microscope and observing the causative organisms. Treatment is tetracycline or erythromycin 500 mg by mouth four times a day for 10 days. When the victim ingests the antibiotics, he may suffer a high fever and low blood pressure (shock—see page 60) as a reaction to the death of the organisms within his bloodstream. Therefore, if you suspect relapsing fever, unless the victim is extremely ill, it is best to have him treated in a hospital, where this reaction can be anticipated and managed. If you are forced to treat in the field, be certain that the victim is well hydrated (see page 208), and administer a lower dose (250 mg) of antibiotic for the first four doses.

TYPHOID FEVER

Typhoid fever is caused by the bacteria Salmonella typhi, which are transmitted among humans through ingestion of contaminated food or water. Most cases are acquired abroad under conditions of poor hygiene.

After an incubation period of 10 to 14 days, victims suffer fever with or without diarrhea and abdominal pain. Most victims also complain of headache, fatigue, and loss of appetite. “Rose spots,” which are 2 to 4 mm red spots on the trunk that blanch (lose their color) when pressed, are seen in some cases. The liver may become inflamed.

Most cases resolve in 3 to 4 weeks. The seriously stricken individual may suffer a severely inflamed bowel, bleeding from the gastrointestinal tract, pneumonia, heart failure, severe fever, and death.

A physician who diagnoses typhoid fever will treat the victim with an intravenous antibiotic. The layperson can use trimethoprim-sulfamethoxazole; administer one double-strength tablet twice a day for 2 to 3 weeks. You can also use ampicillin 100 mg/kg (2.2 lb) of body weight in four divided doses for 2 to 3 weeks. It is important to keep the victim from becoming dehydrated (see page 208).

Injectable and oral vaccines (see page 456) to prevent typhoid fever are available to people traveling to areas of high risk.

LASSA FEVER

Lassa fever is a viral disease transmitted to humans principally through the body secretions of the Mastomys natalensis rat. It occurs primarily in sub-Saharan West Africa.

The infected victim suffers a gradual onset of headache, fever, and fatigue. There is often a severe sore throat, and there may be diarrhea and/or reddened eyes. Victims often complain of chest pain behind the breastbone, which may be caused by inflammation of the throat and esophagus. Roughly a quarter of victims develop bleeding complications. If the case is nonfatal, resolution begins in 8 to 10 days. In a fatal case, the victim progresses to develop altered mental status, shock, and severe breathing disorders.

The viral hemorrhagic (bleeding) fevers (Lassa, Marburg, Ebola, and Crimean-Congo) can all be spread among humans by transfer of secretions (blood and body fluids). Therefore, it is important to isolate suspected victims as best as possible from other humans during their care. Transfer to a medical facility for specific drug therapy may be critical to survival. Field care is supportive and similar to that for yellow fever (see page 150).

SCHISTOSOMIASIS

Schistosomiasis is a term that describes a variety of diseases caused by different species of parasitic flatworms. The intermediate hosts are freshwater snails, which release the immature infective stages into the water; thus, the infections are acquired by people who bathe or swim in contaminated water. The early symptoms caused by all of the species of worms are similar. When the fork-tailed cercariae (early stages of the immature worm) penetrate the skin, they cause itching and a rash at the site of entry that may begin within a few hours to a week after exposure and lasts for 1 to 2 days. Four to 6 weeks later, the victim shows loss of appetite, fatigue, night sweating, hives, and late-afternoon fever lasting 5 to 10 days (“snail,” “safari,” “Katayama,” or “Yangtze River” fever). After a few months, the different species cause specific organ damage.

Schistosoma haematobium is prevalent in Africa, the Middle East, the islands of Madagascar and Mauritius, and India. The worms take residence in the blood vessels of the bladder and genitalia, and induce bloody, painful, and frequent urination. The other four species of worms cause scarring in the intestines and liver. S. mansoni is prevalent in Africa, the Arabian peninsula, Madagascar, Brazil, Suriname, Venezuela, and some Caribbean islands. The worms take residence in the blood vessels surrounding the large bowel and induce bloody and mucus-laden diarrhea. In late stages of the disease, the liver can be severely damaged. S. japonicum is prevalent in China, the Philippines, Japan, and the island of Sulawesi. The worms take residence in the blood vessels supplying the small bowel and induce severe, bloody, and mucus-laden diarrhea. S. intercalatum infections occur in sub-Saharan Africa and S. mekongi infections along the Mekong River in Cambodia and Laos. “Katayama fever” consists of fever, headache, muscle aches, abdominal pain in the right upper quadrant (liver), and bloody diarrhea. This occurs 2 to 6 weeks after the onset of schistosomiasis.

The diagnosis is usually made by identification of schistosome eggs in feces or urine. Treatment for schistosomiasis includes the prescription antihelminthic (antiparasitic) drug praziquantel.

To prevent schistosomiasis, it is necessary to prevent the entry of cercariae into the body. In a region of high risk, it is unwise to bathe or swim in an untreated pond or stream. Shallow, stagnant water is more contaminated than that in swift-moving currents. Always wear hip boots or waders when passing through streams or swamps. If contact with water occurs, apply rubbing alcohol to your skin and briskly towel off. Boil or disinfect all bathing water, or store it for 3 days (the life span of the cercariae) before using it; also be certain that it is free of snails. Artemether is a drug that can be given alone or in combination with praziquantel to prevent schistosomiasis in high-risk situations. There is not yet an effective repellent or vaccine against schistosomiasis.

ROCKY MOUNTAIN SPOTTED FEVER

Rocky Mountain spotted fever is caused by Rickettsia rickettsii, a tick-borne parasite. The disease is most commonly noted in late spring and early summer, when people are more likely to be outside and become hosts for the dog tick (Dermacentor variabilis) or western wood tick (D. andersoni). Other ticks can also carry the parasite. Most infections are reported in the southeastern states: North Carolina, South Carolina, Texas, Tennessee, Virginia, Maryland, and Georgia.

The incubation period is 2 to 14 (average 7) days after the tick bite, at which time a high fever begins abruptly. Two to 6 days after the onset of fever, the red-spotted rash typically begins on the hands (including the palms), wrists, feet (including the soles), and ankles, and then spreads toward the trunk. The face is less often involved. At first, the rash is composed of pink spots that blanch with pressure; they later become darker red or purplish. As the disease advances, the spots coalesce to form purple blotches. However, some victims never develop a rash (Rocky Mountain “spotless” fever).

Other symptoms that begin before the onset of the rash include headache (common), chills, joint and muscle aching, cough, puffy eyelids and face, swollen hands and feet, reddened eyes, abdominal pain, nausea, and vomiting. Severe cases can affect multiple organ systems and cause death.

If you suspect that someone is suffering from Rocky Mountain spotted fever, seek a physician’s help immediately. Doxycycline (adult dose, 100 mg twice a day) or tetracycline (adult dose, 500 mg four times a day; pediatric dose, 10 mg/kg four times a day) should be given for 6 days, or continued until the victim is without fever for 3 days. Although it is generally not recommended that you administer doxycycline or tetracycline to a pregnant woman or to a child less than 6 years of age, because of the risk of tooth discoloration or abnormal bone development (the latter in a fetus during pregnancy), in a case of suspected Rocky Mountain spotted fever when a physician is not available to administer an alternative antibiotic, doxycycline or tetracycline should be given.

COLORADO TICK FEVER

Colorado tick fever is caused by a virus transmitted to humans by the wood tick Dermacentor andersoni, and perhaps by other species. It is a seasonal illness that occurs from late March to early October, with peak incidence in May and June, usually in people who recreate outdoors.

The usual incubation period—from tick bite to symptoms—is 3 to 6 days. The victim complains of sudden onset of fever, severe headache, muscle aches, and fatigue. Other symptoms may include aversion to light, eye pain, loss of appetite, abdominal pain, and nausea and vomiting. Only 5% to 10% of victims develop a skin rash. The hallmark feature, which is only observed in half of victims, is a distinctive fever pattern. There is a fever for 2 to 3 days, a 1- to 2-day remission, and then an additional 2 to 3 days of fever. Permanent effects and serious complications are rare, but do occur, more commonly in children under age 10 years.

A victim of Colorado tick fever may require 3 weeks or longer to recover fully; the most common persistent symptoms are fatigue and weakness. However, infection appears to confer lifelong immunity to subsequent exposures to the virus.

LYME DISEASE

Lyme disease, caused by infection with the spirochete Borrelia burgdorferi, is the most common tick-borne illness in the United States. Occurrence is most frequent in summer and early autumn, during peak outdoor activities. The two hard ticks implicated in transmission of the spirochete from mammal to mammal (for example, from white-footed mouse Peromyscus leucopus to the white-tailed deer Odocoileus virginianus in the South; from the dusky-footed wood rat Neotoma fuscipes and the California kangaroo rat Dipodomys californicus to larger mammals in northern California) are Ixodes scapularis (deer tick) in the Northeast, South, and Midwest, and I. pacificus (western black-legged tick) in the West.

The adult ticks of the these species are extremely small—about the size of a sesame seed. Worse yet, the disease can be transmitted by the nymphal forms, which may appear only as minuscule black spots on the skin. Other potential carriers of Borrelia burgdorferi in the United States include the dog tick, wood tick, rabbit tick, and Lone Star tick (Amblyomma americanum); however, these ticks may not transmit the disease. Lyme disease has been reported in Canada, the Soviet Union, Australia, Europe (linked to the sheep tick I. ricinus), Scandinavia, Japan, and China. In Asia, the culprit tick is I. persulcatus.

The distinctive skin lesion of Lyme disease, erythema (chronicum) migrans, appears 3 to 32 days (usually, about a week) after the tick bite. It is attributed to B. burgdorferi that are spreading locally in the skin, and is usually found on the trunk, upper arm (or armpit), or thigh as a small red spot that expands into a large (average 7 in or 18 cm, but up to 30 in or 76 cm, in diameter) and irregular circle or oval with a red, raised, or flat outer border surrounding paler (“fading,” but slightly red) skin in the center. The rash may itch or burn, and is warm to the touch. The initial central spot may turn into a blister or small ulcer, or it may turn blue in color. In some cases, multiple similar red areas appear simultaneously, occasionally within the larger primary lesion, but never on the palms or soles. These areas clear spontaneously over 1 to 14 (average 4) weeks. Variations of the rash include diffuse hives or a more measles-like eruption. An untreated victim may develop recurrent rashes 1 to 14 months after the initial rash disappears.

Within days to weeks of infecting a human, the B. burgdorferi organisms spread from the skin through the bloodstream and lymphatic system to affect other organs. Therefore, appearing just before, or coincident with, the skin rash(es) are flu-like symptoms that include muscle aching (particularly of the calves, thighs, and back), stiff neck, fatigue, low-grade fever, chills, painful joints, loss of appetite, nausea, cough, sore throat, swollen lymph glands, enlarged spleen, headache, abdominal pain (particularly in the right upper quadrant), irritated eyes (conjunctivitis), swelling around the eyes, and aversion to light. Most of the symptoms disappear in 2 to 3 weeks (along with the rash), but fatigue and muscle aching may last for months.

More serious symptoms include severe headaches and a stiff neck suggestive of meningitis (see page 174), confusion, profound sleepiness or insomnia, memory disturbances, emotional changes, and poor balance. Pain in the joints and symptoms of hepatitis may also occur.

Pets can also contract this disease, suffering lameness, swollen joints, lethargy, and loss of appetite.

If Lyme disease is not treated with an antibiotic, the disease can progress to facial paralysis and severe heart and nervous system disorders weeks to months after the initial rash disappears. Months or years later, up to 60% of untreated victims will suffer arthritis.

Antibiotic therapy for Lyme disease at the time of the initial rash or symptoms should be given for 2 to 3 weeks. Treatment may be extended to 4 weeks if symptoms persist or recur. For an adult, use doxycycline 100 mg twice a day. An alternative is amoxicillin 500 mg orally three times a day. If the victim is allergic to tetracycline and amoxicillin, he may take cefuroxime axetil 500 mg orally twice a day or erythromycin 250 mg orally four times a day. A child should be treated with amoxicillin 17 mg/kg (2.2 lb) of body weight (up to 250 mg) three times a day. If the child is allergic to penicillin, administer cefuroxime axetil 125 mg or 15 mg/kg (2.2 lb) of body weight or erythromycin 250 mg or 10 mg/kg (2.2. lb) of body weight 3 times a day. Nearly 15% of persons treated with antibiotics for Lyme disease in this fashion may develop fever, flushed skin, and low blood pressure within 24 hours of treatment. This may require physician intervention for intravenous fluids.

A physician may elect to treat certain Lyme disease victims with a daily injection of ceftriaxone for 2 weeks. There are occasional treatment failures; these people may require hospitalization for another intravenous antibiotic.

Prevention is key. Avoid tick bites by wearing proper clothing (light colored for spotting ticks, tightly woven collared shirts, closed boots, long sleeves and pant legs, hats) impregnated with 0.5% permethrin (Permanone) insecticide or N,N-diethyl-3-methylbenzamide (DEET) repellent in the critical locations (see page 390). When traveling in tick country, keep shirts and pant cuffs tucked in. All hair-covered areas and warm, moist locations on the skin should be inspected carefully. Any tick found on the skin should be removed promptly and properly (see page 386). Following a tick bite, watch for the characteristic rash and symptoms. Some authorities believe that a tick must be attached to a human for at least 36 to 48 hours to transmit Lyme disease, but this has not yet been proven. Most authorities agree that the risk of transmission increases with the duration of tick attachment.

It has not yet been proven that administration of an antibiotic to every person bitten by an Ixodes tick is a cost-effective method to prevent this disease. However, in an area where carrier ticks and the disease are frequent, it is not unreasonable to administer an appropriate antibiotic within 72 hours following removal of an embedded or blood-engorged tick. Suggested drug regimens include amoxicillin 500 mg three times a day or doxycycline 100 mg twice a day for 10 days. In the absence of an allergic reaction to the antibiotic, this therapy is generally safe.

EHRLICHIOSIS AND ANAPLASMOSIS

Human ehrlichiosis (there is also a canine form) is present in two forms, one caused by a rickettsial organism known as Ehrlichia chaffeensis, which is spread by Amblyomma americanum tick bites, and the other caused by the rickettsial organisms E. phagocytophila and E. equi, spread by Ixodes tick bites. Infection is usually acquired by a person who inhabits a rural environment. The average incubation period after a bite is approximately 7 to 10 days. The victims, who are more commonly middle-aged adults than children and young adults, complain of a flu-like syndrome with high fever, chills, fatigue, headache, muscle aches, vomiting, and a variety of skin rashes, which can be punctate, bumpy, like tiny bruises, or broad and reddened. A victim often has decreased counts of various types of blood cells, as well as liver dysfunction. The treatment is tetracycline 500 mg four times a day, or doxycycline 100 mg twice a day, for 10 days. The few children who have been diagnosed with ehrlichiosis have been treated with doxycycline 3 mg/kg of body weight in two divided doses per day. Untreated or treated after a delay in diagnosis, up to 15% of victims can develop severe infections, kidney failure, bleeding disorders, seizures, and/or coma.

Human anaplasmosis, which was formerly called human granulocytic ehrlichiosis, is caused by infection of white blood cells by a bacterium named Anaplasma phagocytophilum. Like ehrlichiosis, anaplasmosis is disseminated by bites of Ixodes ticks, the blacklegged tick (I. scapularis) in the Northeast and upper Midwest, and the western blacklegged tick (I. pacificus) on the West Coast. Infected persons have the onset of illness 5 to 21 days after a bite with symptoms of fever, headache, fatigue, and muscle aches, which may progress to more serious illness affecting the kidneys, central nervous system, lungs, and blood system. The treatment is the same as for ehrlichiosis.

BABESIOSIS

Babesiosis is caused by protozoan parasites that invade human red blood cells. They are transmitted from mammals and rodents to humans by the bite of certain hard ticks. For instance, Babesia microti in New England is transmitted by the northern deer tick Ixodes scapularis, which can also transmit the spirochete agent of Lyme disease.

An infection manifests itself in a human with symptoms of fatigue, loss of appetite, and weakness, followed within a few days to a week by fever, sweats, and muscle aches. Less common symptoms include headache, nausea, vomiting, and chills. There is rarely a rash. The victim may suffer anemia and an enlarged spleen. A person who no longer has a spleen may suffer a more serious or prolonged illness.

A physician can make the diagnosis by observing the parasites in a smear of human blood under the lens of a microscope. Most victims recover without treatment. In severe cases, a physician may administer drugs, such as quinine and clindamycin.

TRICHINELLOSIS (TRICHINOSIS)

Trichinellosis (trichinosis) is a disease that occurs in humans who consume the larvae of Trichinella species (such as spiralis and nativa) that have encysted in animal muscle tissue (meat). Most of us are familiar with the risk associated with eating undercooked pork, but be aware that cases have resulted from consumption of horse meat, wild boar, bear, walrus, and cougar, the latter in jerky form (which was brined and smoked, but never heated during preparation). Squirrels, woodchucks, capybaras, mice, and rats are infected in nature.

Victims of trichinellosis first develop gastrointestinal distress (nausea, vomiting, diarrhea, and abdominal pain) during the week following ingestion of infested meat. This may continue for 4 to 6 weeks. During the second week, when the larvae are invading human muscle tissue, high fever, muscle aches, swelling (edema, puffiness) of the soft tissues around the eyes, weakness, skin rash, and joint aches develop. There may be tiny red hemorrhages under the fingernails or visible within the skin. In addition, analysis of human blood shows an unusually high count of eosinophils, which are a cell type associated with allergies and certain parasite infestations.

The migrating larvae can cause damage to the lungs (cough, bloody sputum, shortness of breath, pain with breathing), heart, and brain.

The larvae encyst in the muscle tissues, beginning the second or third week of infection, which causes muscle aches and stiffness. Then the larvae die; they become calcified 6 to 18 months after the infection first occurred.

The definitive diagnosis is made in humans by a blood test or muscle biopsy (examining a small piece of muscle harvested from the patient for Trichinella cysts and muscle inflammation with a concentration of eosinophils). Treatment for a person with trichinellosis is not yet totally satisfactory; it involves administration of the drug thiabendazole or mebendazole.

Although most species of Trichinella are killed by freezing, there are freeze-resistant strains, so all meat that is at a high risk for carrying the parasite should be cooked thoroughly to a temperature of at least 150°F to 170°F (65.6°C to 77°C), which generally occurs when the meat turns from pink or red to gray. Certain brining solutions may kill Trichinella; however, the curing temperature must be sufficiently high.

LEPTOSPIROSIS

Leptospirosis is caused by the spirochetes of Leptospira species. The organisms are shed in the urine of wild and domestic animals, including cows, dogs, and pigs. Humans acquire the disease by contacting contaminated soil or water, which includes freshwater ponds and streams. The spirochetes can enter through nicked or abraded skin, through the mucous membranes of the eye and mouth, or by being ingested.

After an incubation period of 5 to 14 days, many victims display fever, chills, fatigue, muscle aches, headache, swollen lymph glands, and red eyes without a discharge. Nausea, vomiting, abdominal pain, and cough are common symptoms as well. This presentation lasts for about a week, and then is followed by a few days of improvement, after which a second stage of the disease begins. This is characterized by more muscle aches, nausea and vomiting, and a diffuse skin rash (red or purplish patches of skin). A sore throat, enlarged spleen, abnormal heart rhythms, low platelet count, and enlarged liver with jaundice may develop. In very severe cases, the victim may suffer from kidney and liver dysfunction, and even bleeding from the lungs.

The treatment is doxycycline 100 mg by mouth twice a day, or tetracycline 500 mg four times a day, for 7 days. Other antibiotics that can be used are amoxicillin, cefuroxime axetil, penicillin, and erythromycin.

To avoid infection, it is best not to swim in freshwater ponds and streams likely to be heavily contaminated by urine from livestock or wildlife.

TULAREMIA

Tularemia is caused by the bacterium Francisella tularensis, which can be transmitted to humans by tick bites, or by handling, skinning, or eating improperly cooked infected rabbit meat. Rarely, it can be transmitted from a cat, bear, deer, beaver, or muskrat. Even more rarely, it can be inhaled (associated with gardening and lawn care) and cause pneumonia.

There are multiple clinical presentations of the disease, with combinations of the following signs and symptoms: painful and tender ulcers on the hand (from handling an infected animal) with associated swollen lymph glands behind the elbow and in the armpit; swollen lymph glands in the groin, associated with insect bites of the legs; sore throat; conjunctivitis in one eye with a swollen lymph gland in front of the ear on the same side; fever; chills; weakness; pneumonia; and weight loss.

A physician will use blood tests to confirm the diagnosis. Treatment is best rendered with intramuscular injections of streptomycin. If the victim cannot be brought to medical attention promptly, therapy may be initiated with tetracycline 500 mg four times a day, or ciprofloxacin 750 mg twice a day.

MENINGOCOCCAL DISEASE (INCLUDING MENINGITIS)

One of the most feared infectious diseases is meningitis caused by the bacterium Neisseria meningitidis (meningococcus). The infection can appear in outbreaks, most commonly abroad, particularly in sub-Saharan Africa and China. The infection is spread in the respiratory secretions of humans.

The disease appears in many forms, the most common of which are meningitis, pneumonia, and disseminated bacterial infection. The typical presentation of meningitis is fever, headache, and a stiff neck (see page 174). If the cause is meningococcus, the victim may develop a skin rash, which consists of red dots or bumps, or a flat, more patchy dark red discoloration. If the dark red dots begin to enlarge and coalesce into large purplish bruise-like discolorations, this is a bad sign. In the worst cases, the victim develops shock, respiratory failure, diffuse bleeding, and death. Approximately 1 in 10 victims of meningococcal meningitis dies.

This is a true emergency. The victim needs large doses of intravenous antibiotics, such as ceftriaxone. If these are not available, administer a high oral dose of penicillin, cephalexin, cefixime, cefpodoxime, or amoxicillin–clavulanate acid for 10 days. If the victim is allergic to penicillin, use trimethoprim-sulfamethoxazole or ciprofloxacin. Ciprofloxacin may also be administered to all close (“household”) contact adults in a single dose of 500 mg. Azithromycin in a single dose of 500 mg by mouth may also be effective for prophylaxis against the disease in contacts. Rifampin may also be used for this purpose in adults (600 mg a day by mouth for 2 days) and children (younger than 1 month: 5 mg/kg by mouth every 12 hours for 2 days; older than 1 month: 10 mg/kg by mouth every 12 hours for 2 days). A physician may elect to prescribe an injection of ceftriaxone for this purpose.

An effective meningococcal vaccine is available (see page 453)

RABIES

Rabies is discussed on page 410.