Dr. Rose Recommends for Healthy & Safe Travel
Health Guide Chapter 9
- Travelers must be aware of how to protect themselves against insect-borne diseases, particularly malaria, yellow fever, dengue fever, Japanese encephalitis, and leishmaniasis.
- Yellow fever, found only in Africa and South America and transmitted by a day-biting mosquito, is preventable by immunization. The yellow fever vaccine, however, can sometimes cause adverse side effects in older individuals and should be administered in this age group only when there is the real risk of exposure.
- Dengue is the most common arthropod-borne virus infection globally, a viral infection transmitted by daytime-biting mosquitoes in the Caribbean, Central and South America, Africa, and Southeast Asia. Symptoms can be severe and disabling and include headache, muscle and joint pain, rash and fever. A variant, dengue hemorrhagic fever, is fatal in some cases. There is no vaccine; mosquito-bite prevention measures, using DEET and permethrin, will significantly reduce the risk of infection.
- Chikungunya fever is closely related to dengue fever, but is less apt to cause fatalities. There is no vaccine.
- Zika virus is a similar virus that causes brain damage in fetuses but otherwise causes only mild symptoms. Pregnant travelers and those planning to conceive, are advised not to travel to areas where the virus is reported.
- A night-biting mosquito transmits Japanese encephalitis, a potentially serious but vaccine-preventable viral infection of the brain that is found only in rural South and East Asia. Because the risk to travelers is low, only those traveling in rural farming areas for more than 3 to 4 weeks, or during an epidemic, should consider being vaccinated.
- Leishmaniasis is a parasitic disease transmitted by sand flies. The majority of cases are clustered in several regions: 90% of visceral leishmaniasis occurs in eastern India, Bangladesh, Nepal, Brazil, and Sudan; 90% of cutaneous leishmaniasis cases are from Iran, Iraq, Saudi Arabia, Syria, Afghanistan, Brazil, and Peru.
- Miltefosine is a new oral agent used with success in India for the treatment of visceral leishmaniasis, where resistance is 40%.
Overview of Insect-Borne Diseases
This chapter describes a number of important but rather uncommon (at least for the traveler) diseases caused by viruses, parasites, and bacteria. Unlike a common disease such as hepatitis A, these insect-borne diseases often require the diagnostic and treatment expertise of a travel/tropical medicine or infectious disease specialist. This chapter also underscores the importance of insect-bite protection measures because there are no vaccines available for most of these diseases.
In 1900, Dr. Walter Reed demonstrated that yellow fever is a viral illness transmitted by mosquitoes. The disease is so named because jaundice, the result of liver damage, is a common sign of this illness.
There are two distinct cycles of transmission, but the resulting disease is the same. Urban yellow fever is transmitted by an Aedes aegypti mosquito from an infected person to another person. In jungle yellow fever, mosquitoes transmit the infection between nonhuman primates (e.g., monkeys) and humans or vice versa.
Yellow fever occurs in tropical areas of certain countries in Africa and South America. These countries comprise the yellow fever endemic zones. Interestingly, there is no yellow fever in other regions with warm climates and Aedes mosquitoes, such as the Middle East, Southeast Asia, and the Pacific. The reason for this has never been clearly understood.
Since the 1980s, yellow fever has re-emerged across Africa and South America. In Africa, both jungle and urban transmission cycles occur. The largest number of cases in Africa has been reported from Nigeria. In 1992, yellow fever reappeared in Kenya after an absence of 50 years, and in 1994 and 1995, Gabon reported its first outbreak ever. Outbreaks have also been reported from Cameroon, Ghana, Liberia, Senegal, and Sierra Leone.
In South America in 1995, Peru experienced the largest yellow fever outbreak from any country in South America since 1950, and in 1998, 45% of the world’s cases were documented there. Between 1985 and 1998, yellow fever cases have been reported from Bolivia, Brazil, Colombia, Ecuador, and Peru. In South America, the jungle transmission cycle predominates, and about 80% of yellow fever cases are reported in adult male forest workers. Urban yellow fever has not been reported from South America since 1954, but the Aedes aegypti mosquitoes have reinfested many tropical cities and some suburban areas of South America, setting the stage for potential urban outbreaks of this disease.
Yellow fever is underreported; epidemiological investigations have found the true number of cases to be 10 to 500 times higher than the number reported. Among unvaccinated individuals, it is estimated that the risk of yellow fever in endemic areas in South America is approximately 1:25,000 per 2-week stay. However, in Africa, during epidemics, the risk is estimated to be 1:250; between epidemics 1:2,500 per 2-week stay.
Most yellow fever infections are mild and go unrecognized, but severe, life-threatening illness occurs in about 15% of people exposed to the disease. Symptoms of severe illness start with fever, headache, muscle aches, nausea, abdominal pain, and vomiting. These acute symptoms last for 3 to 4 days and are followed by a toxic phase characterized by jaundice, vomiting of blood, bloody stools, coma, and, in 50% of severe cases, death.
The differential diagnosis includes malaria, leptospirosis, viral hepatitis, typhus, dengue fever, and other viral hemorrhagic fevers. The laboratory diagnosis of yellow fever can be made by measuring IgM antibody response.
Specific drug treatment is not available. Supportive care is indicated.
Vaccination—The best way to prevent yellow fever is by immunization and the current vaccine is highly effective. Most travelers to rural areas of endemic-zone countries should be immunized. To meet international requirements, the vaccine must be administered at least 10 days before arrival when administered for the first time. However, booster doses are effective immediately.
Mosquito Protection Measures All travelers should take measures to prevent mosquito bites at dawn and dusk when Aedes mosquitoes are most likely to bite. These measures include applying a DEET-containing insect repellent, wearing permethrin-treated clothing, eliminating indoor mosquitoes through screening and spraying, and sleeping under a permethrin-treated bed net.
This viral illness occurs in more than 60 tropical and subtropical countries, with more than one half the population of the globe at risk for infection. The incidence and geographic distribution of the disease have greatly increased in recent years. Dengue (pronounced DENG-ee) is now prevalent in the Caribbean, Central and South America, Mexico, the Pacific Islands, and South Asia and Southeast Asia. In the United States, the majority of dengue fever cases occur in tourists who have returned from Puerto Rico, the Virgin Islands, Mexico, and Thailand. Unless there is an epidemic in progress, the risk of acquiring dengue by the average tourist is low, perhaps 1:15,000 to 30,000 travelers.
Dengue is spread by Aedes mosquitoes. These mosquitoes feed during the day, with most biting activity in the morning for several hours after daybreak and in the late afternoon for several hours before dark, but the mosquito may feed at any time during the day, especially indoors, in shady areas, or when it is overcast. Dengue is primarily an urban disease because Aedes mosquitoes usually breed in small pools of stagnant water that collect in discarded tires, buckets, bottles, flower vases, barrels, etc. There are four (serotypes) dengue viruses. If you are infected with one type of virus, you will gain lifelong immunity against that particular serotype, but not against the other serotypes. In fact, subsequent infection with a different serotype may result in more severe disease including dengue hemorrhagic fever or dengue shock syndrome. Severe infections, however, are very rare among travelers.
Dengue virus infections may be asymptomatic or may lead to a range of symptoms, including death. The vast majority of infections, especially in children younger than 15 years of age, are asymptomatic or minimally symptomatic. More severe illness is seen with increasing age, or with repeat infections with a different serotype, especially in children living in endemic areas.
Dengue Fever (DF) Typical symptoms include chills and fever (“breakbone fever”); severe headache, especially behind the eyes; muscle and joint pain; nausea and vomiting; flushing of the face, neck, and chest; and a rash. The rash appears in 3 to 4 days and may be confused with measles. Low white blood cell count and low platelet count occur frequently. In uncomplicated cases, acute symptoms resolve in 5 to 7 days, but fatigue may linger for many weeks.
Note: Other illnesses that can mimic dengue include malaria, leptospirosis, typhoid, measles, and chikungunya fever. You should be checked immediately for malaria if you develop fever while in or after visiting a malaria-endemic area.
Dengue Hemorrhagic Fever (DHF) This is a severe, sometimes fatal form of dengue fever that rarely strikes Western tourists. Dengue hemorrhagic fever is diagnosed when there is minor or major bleeding, low platelets, and evidence of plasma leakage from capillaries into the tissues or body cavities. A progressively decreasing platelet count and a rising hematocrit from ongoing plasma loss herald the impending onset of dengue shock syndrome (DSS).
Treatment consists of bed rest, fluid replacement, and analgesics. Aspirin and other nonsteroidal anti-inflammatory drugs should be avoided because they interfere with platelet function and may promote further bleeding. Antibiotics and steroids are not beneficial. The prognosis in DHF and DSS depends on the prevention or early recognition and treatment of shock. Early, judicious treatment with intravenous fluids and plasma expanders can keep mortality below 1%. Once DSS is established, mortality can exceed 40%.
No vaccine is available. Reduce your risk by preventing mosquito bites. Remember, the Aedes mosquito is a day biter and found mostly in urban centers. Follow the guidelines in Chapter 7.
Japanese encephalitis (JE) is a mosquito-transmitted viral illness and the number one cause of brain infection (encephalitis) in Asia and the Western Pacific. More than 50,000 of cases of JE are reported annually from Southeast Asia, India, China, Japan, and Korea.
Japanese encephalitis (encephalitis = inflammation of the brain) occurs in rural- agricultural areas throughout Asia. In temperate regions such as the People’s Republic of China, Japan, and Korea, JE transmission is highest from April to September. In northern India and Nepal, peak transmission is from June to November. In the tropical regions of Asia and Oceania, JE occurs year round.
The virus of Japanese encephalitis is transmitted by Culex mosquitoes. These mosquitoes breed where there is abundant water, such as in rice paddies, and feed primarily on birds and local domestic animals, usually pigs. Visiting a rural-agricultural rice-growing, pig-farming region, therefore, can put you at risk. About 1% to 3% of the Culex mosquitoes in endemic areas are infective. Because these mosquitoes are night feeders, there is less risk of JE transmission during the day.
The average tourist is not at risk. If you are a short-term traveler, and if you are visiting only urban areas, your risk of getting JE is very low—approximately one in one million. You will be at greater risk if living in rural agricultural (rice-growing, pig-farming) areas during the season of peak transmission. Your risk then rises to approximately 1 in 5,000 per month of exposure. Of the small number of Americans who have developed this illness in the last 2 decades, most were military personnel or their dependents.
Nausea, vomiting, headache, and fever are the most frequent symptoms. A severe attack may cause seizures, paralysis, confusion, coma, and death. Fortunately, most JE infections are asymptomatic—only 1 in 250 individuals who are infected becomes sick. Unfortunately, if one does develop symptoms, the resulting illness can be severe, with death occurring in up to 25% of patients, and permanent neurologic damage in about 30%.
There is no drug treatment for JE. Good nursing care is essential in severe cases.
Mosquito Protection Measures All travelers should take measures to prevent mosquito bites, particularly during the evening and nighttime when staying in rural areas.
Vaccination See Table 3.2, Chapter 3, for JE vaccine schedule, indications, precautions, and contraindications.
African trypanosomiasis, or sleeping sickness, is transmitted by the bite of a tsetse fly. This disease is endemic in sub-Saharan Africa, and major outbreaks are now occurring in Sudan, Uganda, Congo, and Angola. The number of cases is estimated at 300,000, with about 60 million people at risk. Sleeping sickness, however, almost never occurs in tourists, although occasional cases are reported in travelers, usually those visiting game parks. Long-term travelers or expatriates living in rural endemic areas may be at slightly increased risk.
There are two forms of this disease. Gambian, or West African, trypanosomiasis (caused by Trypanosoma brucei gambiense) is a chronic disease that takes several years to reach the advanced stage. It occurs primarily in the forested areas of western and central Africa. Rhodesian, or East African, trypanosomiasis (caused by Trypanosoma brucei rhodesiense) manifests more acutely and progresses more rapidly. It occurs primarily in the savannah and woodlands of eastern and southern Africa and is the form seen (rarely) in travelers.
Symptoms start 5 to 15 days after the bite of an infected fly. (Note: Tsetse fly bites may be quite common on safari but only a very small percentage of tsetse flies are infected. Tsetse flies are not affected by insect repellents and the bites are not particularly painful). An inflamed nodule (inoculation chancre) develops at the site of the bite and may measure one half inch or more in diameter. Chancres are typically seen only in T. rhodesiense infections. Other symptoms include fever, headache, rash, lymph node swelling, enlarged spleen, swelling of the face and joints, and, occasionally, inflammation of the heart. In East African disease, the brain is invaded early, and, unless treated, progresses to lethargy, coma, and, ultimately, death within 6 weeks to 9 months. The onset of West African trypanosomiasis is more insidious. A localized skin lesion is the first symptom. Fever, rash, and lymph node swelling take weeks to months to appear. Brain damage symptoms occur later. The diagnosis of East African sleeping sickness is made by demonstrating trypanosomes in blood, chancre, or spinal fluid.
Unlike malaria—where new drugs have become available—sleeping sickness, Chagas disease, and kala-azar are treated with drugs that are decades old and often toxic. The most common treatment for sleeping sickness is melarsoprol, an arsenic derivative that kills as many as 5% of its users.
Management of this disease requires the expertise of a specialist. Suramin is the treatment of choice for early-phase East African (Rhodesian) trypanosomiasis. Melarsoprol, an arsenic compound, is indicated for the treatment of second-stage disease, when there is central nervous system involvement. Treatment of the second stage, however, is long and complicated, and can be hampered by severe side effects. In the early stage, Gambian sleeping sickness may be treated with pentamidine and the 2nd stage with eflornithine.
The only prevention is to avoid the day-biting tsetse fly.
This is a potentially fatal disease, but one that rarely affects travelers. Chagas disease* is caused by a parasite that is most often transmitted by the reduviid (triatomine) bug, known colloquially as the kissing bug. The insect lives in cracks and holes in poor housing, where it bites people, often on the face, while they sleep. Parasites in bug feces deposited on the skin enter the body through the bite or when the bite is scratched. The disease can also be transmitted through blood transfusions, organ transplants, and from mother to child at birth. Oral transmission may occur with the ingestion of food contaminated by feces of infected Triatominae. In 2005, Brazilian health officials reported a widespread outbreak in which Chagas disease was transmitted through the consumption of contaminated sugar cane juice.This mode of transmission may be particularly frequent among the settlers of Amazonian areas.
*This disease, American trypanosomiasis, is named after Carlos Chagas, a Brazilian physician, who first first described it in 1909. The causative organism, Trypanosoma cruzi, is a single-cell parasite.
Chagas disease occurs in Latin America in rural areas extending north from Chile and Argentina to Mexico. The highest incidence occurs in Bolivia, where 20% of the population is infected; Brazil, with a 1.3% global prevalence rate, has 5 million persons with Chagas disease. Prevalence is estimated to be 5% to 10% in Argentina, Honduras, Paraguay, and El Salvador; 1% to 5% in Chile, Columbia, Ecuador, Uruguay, and Venezuela; and less than 1% in Mexico and Nicaragua.
The parasites may cause an acute illness, but more frequently the symptoms are mild or overlooked. Decades later, in about 30% of infected individuals, damage to the heart and/or the gastrointestinal tract becomes evident.
The initial symptoms of Chagas disease are usually mild or nonexistent; less than one-third of persons develop an acute illness and most of these are children and young adults. One to three weeks after insect-bite exposure there may be a swollen nodule or pimple (chagoma) at the inoculation site, accompanied by fever and localized lymph node swelling. A facial bite (which is common) with entry of parasites through the conjunctiva causes painless swelling of the eyelids and conjunctivitis (Romaña’s sign) is considered a reliable diagnostic indicator in suspected cases. Localized symptoms may be accompanied by a flu-like illness with fever, headache, muscle aches, vomiting, and a rash. Some degree of heart muscle inflammation (myocarditis) occurs in 30% of infected people but severe disease, requiring hospitalization, is uncommon.
The chronic phase—After 30-60 days all initial symptoms will have resolved, but the parasites remain active in the body, causing a chronic, but largely silent, infection. By the fourth decade of life, about one-third of chronically infected people will develop symptoms of heart and/or gastrointestinal disease. Cardiac problems include cardiomyopathy, heart block, and heart failure. Chronic enlargement of the esophagus and colon may cause difficulty swallowing, abdominal pain, bloating, and constipation.
Acute Chagas disease may be confused with malaria, mumps, eye infections, sinusitis, and cellulitis of the skin. The diagnosis can be made by identifying T. cruzi parasites under the microscope. Serological testing is useful during the long asymptomatic period or when late-stage disease of the heart or intestine occurs.
The acute illness may be treated with either benznidazole (Ragonil®, Roche) or nifurtimox (Lampit®, Bayer). Neither drug is commercially available in the United States or Canada. Although there is no drug that currently provides satisfactory treatment for chronic Chagas disease, there is an increasing trend to treat silent chronic infections before late-stage illness begins.
Transmission by insect vector occurs primarly in areas where there is poorly constructed adobe-style mud and thatched roof huts. People staying in tourist accomodations are not at risk. If you are sleeping in a structure that is possibly infested, take the following precautions:
- Spray your living and sleeping quarters with an insecticide. (e.g., RAID Formula II Crack and Crevice Spray).
- Use a residual insecticide on the walls and roofs of houses.
- Sleep under a permethrin-impregnated bed net that is tucked under the mattress.
Remember that Chagas disease can also be spread by unscreened blood transfusions, so these should be avoided.
Tick-borne encephalitis (TBE) is a viral disease that occurs in forested areas of the former Soviet Union and northeastern China, eastern and central Europe, and parts of Scandinavia. TBE is transmitted by Ixodid ticks (the same ticks that transmit Lyme disease) and presents a risk to campers and hikers in endemic areas. Activities such as berry and mushroom picking can also put people at risk. TBE can also be transmitted by the consumption of unpasteurized dairy products from infected cows, goats, or sheep.
The greatest risk of disease occurs during periods of high tick activity, starting in the spring when the temperature rises above 6°C (43°F) and usually persists until October–November when the temperature falls. Infective ticks are found in mixed coniferous-deciduous forests, extending into the shrubby forest edge and meadows, as well as along river and stream valleys (including forests bordering large cities).
TBE is caused by tick-borne encephalitis virus, a member of the genus Flavivirus in the family Flaviviridae. It was first isolated in 1937. Three virus sub-types are described: European or Western tick-borne encephalitis virus, Siberian tick-borne encephalitis virus, and Far-Eastern tick-borne encephalitis virus (formerly known as Russian spring summer encephalitis virus).
The Ixodes ricinus tick accounts for TBE in western regions; Ixodes persulcatus to the east. The risk to travelers is low unless extensive outdoor activities are planned in forested regions of endemic areas. Vaccination is recommended for persons planning to expatriate or live for an extended period of time in endemic countries where they will outdoors exposure. Short-stay travelers who plan extensive hiking or camping in brushy or forested areas should consider vaccination (although this may not be possible if residing outside of Europe or Canada. The vaccine is not available in the U.S.). All travelers should exercise insect-bite prevention measures. Tick-bite prevention measures include applying a DEET-containing repellent to exposed skin and permethrin spray or solution to clothing and gear. Preventing tick bites also lowers the risk of Lyme disease.
After an incubation period of 8 days (Range: 4 to 28 days) affected individuals develop fever, fatigue and headache which in about one-third of patients may progress to confusion, imbalance, memory changes, decreasing level of consciousness, and limb paralysis. Unlike polio, the upper extremities, shoulders, and muscles of the neck, rather than the legs, are usually affected. About 25% of patients develop severe disease and 45% of these patients are left with permanent neurologic sequelae. Death occurs, however, in less than 2% of affected individuals.
Treatment consists of supportive care only.
Two TBE vaccines are available in Europe (Encepur, FSME-IMMUN). The FSME–IMMUN vaccine is available in Canada and both are available in the UK by special request. They are administered in three doses over a 12-month period but an accelerated, 3-dose schedule (0, 7, and 21 days) can be employed with Encepur. (There is also accelerated dosing for FSME-IMMUN). To date, no cases of TBE have been reported in vaccinated individuals. Immunization is recommended primarily for people who anticipate intense exposure in endemic areas. It is not recommended, or practical, for the most short-term tourists. Unvaccinated travelers should take precautions against tick bites while in endemic areas. For vaccine schedules, go to Chapter 3.
Filariasis is prevalent throughout the tropics and is a group of diseases caused by thread-like roundworms, called filaria, which are transmitted by various mosquitoes, flies, and biting midges. Varieties of filariasis include (1) lymphatic filariasis—bancroftian and Malayan filariasis (elephantiasis); (2) subcutaneous filariasis-onchocerciasis (“river blindness”); and (3) loiasis.
Bancroftian and Malayan Filariasis
These illnesses are transmitted by several different species of mosquitoes found in tropical regions of Central and South America, the Caribbean, Africa, China, India, Southeast Asia, and Oceania. Infective larvae (microfilariae) are injected into the skin by the bite of the mosquito. The larvae migrate through the lymphatic channels of the skin and become trapped in lymph nodes, where the adult worms develop. For the most part, disease results from damage to lymphatic channels caused by the host’s immune response to adult worms.
Light infections rarely lead to symptoms. Heavier exposure (many bites over many months) is generally necessary to cause symptomatic disease. Initial symptoms consist of redness of the skin and swelling of lymph nodes of the arms and legs, headache, weakness; in some cases muscle pain, coughing, wheezing, and fever occur. Thousands of mosquito bites are often required before symptoms develop. Continued exposure may result in permanent lymphatic obstruction. Progression of the disease, usually observed only in the indigenous population of the endemic area, can lead to the grotesque swelling of the legs (and scrotum in males) known as elephantiasis.
To check for exposure to filariasis, your doctor may wish to examine your white blood cells for eosinophilia, and your blood at midnight for microfilaria because these larvae enter the blood stream mostly between 10 p.m. and 2 a.m. Antibody tests are more than 95% sensitive but are nonspecific. A negative antibody test virtually rules out an active infection.
Treatment of filariasis with diethylcarbamazine (DEC) is effective. The dosage is 6 mg/kg/day for 12 days. Repeated single doses of DEC at monthly intervals for 6 to 12 months appear to increase effectiveness. An effective alternative is albendazole.
See measures described subsequently.
One type of filariasis that is particularly devastating is onchocerciasis, or river blindness, common in equatorial Africa, the Sahara, Yemen, and parts of Latin America (Mexico, Guatemala, Venezuela, Ecuador, Colombia, and Brazil). The disease is transmitted by black flies that breed in vegetation along fast-flowing rivers in these regions. Onchocerciasis is occasionally acquired by long-term travelers such as expatriates and Peace Corps volunteers. In this infection, adult worms are found in nodules under the skin, and microfilaria released from the worms are located in the skin.
Symptoms include a skin rash with intense itching (the most common symptom in infected travelers), skin nodules, swollen lymph glands, inflammation of the eyes, and, in heavy, prolonged infections, blindness.
Symptoms don’t occur for several months or more after exposure. By this time, the blood eosinophil count will usually be elevated; therefore, a complete blood count is often a good screening test. Blood tests (antifilarial antibody and antigen assays) can help establish the diagnosis. (The Clinical and Parasitology section of the National Institutes of Health [NIH] can do the serology testing; call 301-496-5398.) To make a definitive diagnosis, skin snips are obtained to identify filarial larvae.
Treatment is with ivermectin (Stromectol, Merck), 150 to 220 mg/kg in a single dose every 6 months until symptoms do not recur. (Two 6-mg tablets is the usual adult dose.) Ivermectin does not kill the adult worm, but only suppresses symptoms by temporarily reducing the number of larvae in the skin. The CDC’s Parasitology Hot Line (301-496-5398) can answer further questions.
There is no prophylactic drug. Take precautions to prevent bites from day-biting black flies.
This form of subcutaneous (below the skin surface) filariasis is common to the rain forests of West and Central Africa. Loiasis is also the most frequently diagnosed blood filarial infection in travelers returning to North America and the United Kingdom from Africa, though it is still rare. Loa loa larvae (microfilariae) are transmitted by the bite of an infective Chrysops fly, also known in Africa as the deer fly. This is a day-biting fly that breeds in rain forests. After the microfilariae enter the body they develop into adult worms in the subcutaneous tissues (under the skin) and larvae are released into the blood stream.
Symptoms of loiasis are caused by migration of the adult Loa loa worms just beneath the skin. Symptoms—which take 12 months or more to develop—include fever, itching, and skin swellings (Calabar swelling), usually involving the hands, wrists, forearms, or face. Adult worms can also be observed migrating on the surface of the eye, beneath the conjunctiva.
A blood test for eosinophilia and microfilariae (which peak in the blood during the day), and an ELISA screening test, can be done to check for exposure.
Diethylcarbamazine (DEC) is the treatment of choice for Loa loa and consists of a total dose of 75 mg/kg. Although DEC is usually innocuous to humans, serious allergic reactions induced from the destruction of filarial worms may occur. In heavy infections, the full dose of medication should be administered over 2 to 3 weeks. Refractory cases of loiasis have responded to albendazole, 200 mg orally, twice a day, for 21 days.
Prevention of Filariasis and Loiasis
No vaccines are available. You should take measures to prevent insect bites during the day for loiasis and at night for bancroftian filariasis. These measures include applying a Deet-containing skin repellent, wearing permethrin-treated clothing, and sleeping under a mosquito net or in an insect-free room.
Prophylaxis You can take DEC either weekly or monthly to prevent loiasis or lymphatic (bancroftian or Malayan) filariasis. These regimens are recommended rarely to expatriates living in highly endemic areas. Dosage—300 mg DEC weekly to prevent loiasis and 500 mg DEC 2 days each month to prevent lymphatic filariasis.
Note: DEC is available in the U.S. and Canada from the CDC, USA, and Health Protection Branch, Canada, respectively, as an investigational drug for the treatment of filariasis. It is available in many developing countries.
Leishmaniasis is one of the most common parasitic infections in the world, occurring in various forms in 80 countries. The disease is found on all continents except Australia and Antarctica. It is an important public health problem in Mexico, Central and South America, North Africa, sub-Saharan Africa, the Middle East, central Asia, southern Russia, northern China, and India. Scattered areas of disease activity occur in southern Europe, mainly Portugal, southern France, Italy, the Greek isles, the Costa del Sol, and Majorca. In the United States, cases of the disease have been reported in Texas and Oklahoma.
Leishmania are single-cell organisms (protozoa) smaller than a red blood cell. Infection occurs when these tiny parasites are injected into the body by the bite of an infective sand fly. Which form of leishmaniasis (visceral, cutaneous, mucocutaneous) that develop depends on (1) which species of Leishmania (there are about 20) causes the disease; (2) which organs and cells are predominantly infected; and (3) the host’s state of immunity (many cases of leishmaniasis are self-healing). Sand flies are usually found in focal areas on the edge of forested areas or in rodent burrows. They feed from dusk to dawn and have a very limited flight range.
Visceral Leishmaniasis (kala-azar)
Visceral leishmaniasis (kala-azar) is a potentially fatal parasitic disease characterized by fever, hepatosplenomegaly, and pancytopenia. The parasites live in dogs, foxes, rodents and humans; they are transmitted by the bites of sandflies. About 500,000 people are infected annually, with about one-half of the cases in northeast India. Visceral leishmaniasis is also found in and around the Mediterranean Basin, southern Russia, China, East Africa (Kenya, Sudan, Uganda), Central America, Brazil, Venezuela, and Paraguay. In India and China it is widespread throughout rural areas.
Hallmarks of the disease are marked enlargements of the liver and spleen, chills and fever, and anemia. Symptoms include fatigue, weight loss, cough, and diarrhea. Many infections are asymptomatic; however, the parasites may remain dormant and cause severe disease at a later date if the immune system is weakened as in patients with AIDS.
To diagnose visceral leishmaniasis, blood tests and a bone marrow examination and culture may be necessary. An antibody test may be helpful. Diseases that can be confused with visceral leishmaniasis include malaria, typhoid fever, brucellosis, Chagas disease, schistosomiasis, tuberculosis, and amoebic liver abscess. Because massive enlargement of the spleen sometimes occurs, kala-azar can also mimic leukemia or lymphoma.
Treatment optionsfor visceral leishmaniasis are limited. Safe, effective, and affordable treatments for visceral leishmaniasis in regions where the diseaseis endemic are lacking, particularly in formulations that are compatible with rural settings.
Pentostam (sodium stibogluconate), the drug of choice, is given in an intravenous dose of 20 mg/kg daily for 30 to 40 days. Pentostam is a historically effective and affordable pentavalent antimonial compound, but is assocbrated with fatal toxic effects, and in some regions its use has led to the development of resistant strains of Leishmania donovani, with the result that fewer than 50% of treated patients are cured. Pentostam is available from the Parasitic Disease Drug Service Branch of the Centers for Disease Control in Atlanta, Georgia, and the Special Access Program, Health Protection Branch, Health Canada.
In regions where antimony resistance is prevalent, intravenoubr amphotericin B (Fungizone) is used, but it is expensive and may require weeks of hospitalization with intensive clinical and laboratory monitoring. Dosage: 1 mg per kilogram intravenously every other day for 30 days.
Liposomal formulations of amphotericin B (AmBisome), which require a shorter treatment course (5 days) and have fewer side effects, remain unaffordable at nearly 30 times the cost of conventional formulations.
A new oral drug, miltefosine (Impavido), appears to be very effective when administered for 28 days, but it is expensive, and has significant gastrointestinal side effects.
Paromomycin, administered intramuscularly at a dose of 11 mg per kilogram daily for 21 days, has recently been shown to be as effective as amphotericin in the treatment of visceral leishmaniasis (New England J Med. Volume356:2571-2581June 21, 2007) The overall cure rate is 95% and the treatment regimen is far simpler than for amphotericin.
For further information about drug treatment and the serologic diagnosis of leishmaniasis, physicians should contact the Parasitic Disease Drug Service of the CDC at 770-488-7760 or 770-488-7775.
More information about leishmaniasis can be found here.
Cutaneous Leishmaniasis (old world variety)
This infection is characterized by ulcerative skin lesions, and occasionally nodules, caused by one of several species of Leishmania. Local names for this disease include Oriental sore and Baghdad boil. Risk areas include the Mediterranean Basin, the Middle East, Africa (stretching from Senegal to Sudan, Ethiopia, and Kenya), southern Russia, central Asia, and northwestern India.
As the name implies, cutaneous leishmaniasis affects the skin. A variety of lesions can occur: self-healing ulcers, chronic nonhealing sores or ulcers, or nonulcerating and warty skin nodules. Chronic skin ulcers are the most common form of the infection. The skin sites involved are those areas usually not covered by protective clothing, that is, the face, forearms, back of hands, and legs. Symptoms usually occur 2 to 8 weeks after a bite. The lesions may ulcerate and discharge fluid, or they may remain dry. Spontaneous healing tends to occur over a period of several months to 2 years.
Cutaneous leishmaniasis (new world variety)
Two species complexes of leishmania (Leishmania mexicana and Leishmania braziliensis) are responsible for most of the cutaneous leishmaniasis occurring in Mexico and in Central and South America.
Skin nodules and/or ulcers are found on exposed skin areas, usually the face and ear. These lesions appear 2 to 8 weeks after exposure. Spontaneous healing may take 6 to 18 months, or longer.
Mucocutaneous Leishmaniasis (espundia)
This disease is almost exclusively confined to the Western Hemisphere, occurring mostly in the northern half of South America.
This illness occurs when parasites spread from the skin to the mucous membranes of the mouth, nose, and throat. Espundia is usually preceded by a simple skin ulcer, which may heal. Then 1 month to many years after the initial exposure, destructive ulcerations of the nose and mouth occur. Severe disease with disfigurement (espundia) results if treatment is delayed.
To diagnose cutaneous leishmaniasis, tissue samples are obtained from the skin for microscopic examination and/or for culture. Antibody tests are of limited use except in espundia and the nodular form of the disease. The Parasitic Disease Branch of the Centers for Disease Control can identify parasites from tissue, carry out appropriate antibody tests, and offer advice on treatment.
The treatment of choice for large cutaneous lesions is intravenous sodium stibogluconate (Pentostam) in a dose of 20 mg/kg daily for 30 days. Other drugs are available (dapsone, ketoconazole, pentamidine), but their effectiveness depends on the species of infecting parasite, the geographic location where the infection was acquired, and the form of the disease.
This illness in its various forms is transmitted by sand flies. To protect yourself, you must use a DEET-containing insect repellent, treat your clothing with permethrin, and, if necessary, sleep under a mosquito net. There is no vaccine.
Symptoms include chills, fever, nausea, vomiting, severe headache, and a variety of rashes. The most effective treatment is tetracycline, erythromycin, or penicillin. Without treatment, the attack terminates in 3 to 10 days but may recur in a milder form 1 to 2 weeks later. Prevention consists of tick- or louse-bite prevention.
Rift Valley Fever
This is a viral disease of animals, but it can be transmitted to humans by mosquitoes. Rift Valley fever occurs primarily in sub-Saharan Africa. The initial symptoms (chills, fever, headache, backache, weakness, and vomiting) are similar to malaria and dengue, but reddening of the eyes helps distinguish Rift Valley fever from malaria. The illness lasts 4 to 7 days and complete recovery is the rule, but 2% of infected people develop hemorrhagic complications, jaundice, or inflammation of the brain and/or the membranes covering the spinal cord. No specific treatment is available, but ribavirin and interferon may offer some benefit. Prevention entails avoiding mosquito bites.
This mosquito-transmitted viral disease was identified in the 1950s in Africa and Asia. It is responsible for intermittent epidemics, the last outbreaks occurring in 2006 in Kenya and several islands in the Indian Ocean, including the Seychelles, Comoros Islands, and Mauritius. Over 1 million cases have also been reported from India. The disease is transmitted by daytime-biting Aedes mosqitoes.
Symptoms include high fever, a rash, and often severe, crippling joint pain. Treatment is supportive, with hydration and control of pain and inflammation of main importance. Prevention consists of insect-bite prevention measures. There is no vaccine.
West Nile Virus
This mosquito-transmitted virus was first isolated from a patient in Uganda in 1937, spread from Africa to parts of Europe and Asia, suddenly appearing in New York City in 1999. The disease was most likely imported to the United States by air travelers from Europe. In 2002, almost 3,000 cases of neuroinvasive disease (encephalitis) were reported in the United States, but in 2004 the total number of cases declined to 741. The disease is now moving from the East Coast across the country to the west. Almost one-third of the cases of neuroinvasive disease in 2004 occurred in Arizona and California; the other cases occurred throughout the rest of the country. About 20% of persons infected with the West Nile virus develop symptoms and of these only 1 in 140 will develop serious neurologic disease or die. No vaccine is currently available.
Sand Fly Fever
Sand fly fever is a viral disease transmitted by the bite of an infective sand fly and occurs in parts of Europe, Asia, Africa, and Latin America. It occurs primarily in tropical and subtropical areas with hot, dry weather. The vector of the causative virus is the common sand fly, which bites at night.
Symptoms appear 3 to 6 days after the sand fly bite and consist of fever, headache, nausea, weakness, and myalgia. These symptoms may be severe but are rarely, if ever, fatal, and treatment with fluids and analgesics is usually sufficient. Prevention of sand fly fever consists of nighttime protection against insect bites.
This is a mite-transmitted disease found in Asia, the western Pacific, and Australia. Scrub typhus is endemic in a triangular area between northern Japan and southeast Siberia to the north; Queensland, Australia, to the south; and Pakistan to the west. The cause is a rickettsial organism, Rickettsia tsutsugamushi. The disease is transmitted in scrub lands and forest clearings where mites abound on the vegetation.
The larval form, called chiggers, can bite humans who come in contact with vegetation infested with mites. One to three weeks after the mite bite, symptoms occur and consist of chills, fever, rash, lymph node swelling adjacent to the bite, and prostration. A blister, followed by a black scab, or eschar, may occur at the site of the bite. This infection may cause serious illness.
Tetracycline or doxycycline is the treatment of choice.
Prevention consists of using personal protection measures against mite bites. In particular, permethrin-impregnated clothing should be worn (long-sleeved shirts are suggested) with trousers tucked into boots when walking through grasslands and forests in endemic areas. Prophylaxis with 200 mg of doxycycline weekly is effective.
Plague is caused by an infection with bacterium Yersinia pestis, which is carried by rats, other rodents, and their fleas. The disease may occur as isolated cases or in epidemics. Plague is primarily a disease of poverty and the risk to tourists is extremely low. Most cases result from bites from infected fleas, but can also result from the handling of infected animals or from inhaling infectious airborne droplets from persons with plague pneumonia (pneumonic plague).
The most recent epidemics have occurred in East Africa and Madagascar. Recent cases are reported from Madagascar, Tanzania, Congo, Vietnam, Mozambique, Namibia, and Peru. The disease occurs rarely and sporadically in the Southwest United States, with about 10-15 cases reported annually from just a few states (northern New Mexico and Arizona, southern Colorado, California, and southern Oregon.
Symptoms of plague start 2 to 7 days after exposure with rapid onset of fever, chills, headache, generalized aches and pain, and exhaustion. Patients with the bubonic form develop painful swelling of the lymph glands (buboes) in the groin, armpit, or neck; those with the pneumonic form develop a cough and difficulty breathing.
Plague is fatal in 50% to 60% of untreated cases. Early treatment with antibiotics is effective, especially if started within a few hours of the onset of symptoms. The preferred treatment is gentamicin combined with doxycycline. Streptomycin, the drug used most often in the past, is no longer widely available.
The plague vaccine is of unproved effectiveness; the vaccine is no longer available in the United States. Prophylactic antibiotics can prevent plague; they should be taken by certain individuals (medical personnel, relief workers, etc.) when face-to-face transmission of bacteria has potentially occurred or is anticipated. Adults should take doxycycline, 100 mg daily, or tetracycline, 500 mg twice daily; children 9 years of age, or younger, sulfonamides. The most important measure to prevent bubonic plague is to avoid fleas and rodents such as rats, rabbits, squirrels, and chipmunks in endemic areas. Sick or dead animals should also not be handled. Regular use of flea powders on domestic pets having access to both human and rodent habitats is strongly advised in plague-active areas. The application of DEET-containing repellents on exposed skin and permethrin on clothing will reduce the chance of flea bites. People at high risk of exposure to infected fleas should also consider prophylactic antibiotics.
Mediterranean Spotted Fever
This tick-borne rickettsial disease is also known as boutonneuse fever in North Africa, African or Kenyan tick typhus in sub-Saharan Africa, and Indian tick typhus in southern Asia. The disease is caused by Rickettsia conorii and is transmitted by ixodid ticks. Exposure to the ticks usually results from close contact with tick-carrying dogs, rodents, or cattle. Tick typhus is one of the more frequent causes of fever in returned travelers. Symptoms include chills, fever, headache, and a rash. An ulcer with a black crust (eschar) may be noted at the site of the tick bite.
Note: Rickettsia conorii organisms include 4 different subspecies:
Boutonneuse fever and Mediterranean tick fever in Southern Europe and Africa (R. conorii subsp. conorii).
Indian tick typhus in South Asia (R. conorii subsp. indica).
Israeli tick typhus in Southern Europe and Middle East (R. conorii subsp. israelensis).
Astrakhan spotted fever in the North Caspian region of Russia (R. conorii subsp. caspiae).
Read more: http://wwwn.cdc.gov/travel/yellowBookCh4-Rickettsial.aspx and http://www.emedicine.com/med/TOPIC1412.HTM
- Doxycycline 100 mg twice daily x 3 to 5 days
- Chloramphenicol 500 mg four times daily x 3 to 5 days
Take measures to prevent tick bites, especially if engaging in outdoor activities in rural areas. Tick-bite prevention measures include applying a DEET- or picaridin-containing repellent to exposed skin and permethrin spray or solution to clothing and gear. There is no vaccine against this disease.
AFRICAN TICK-BITE FEVER
This spotted fever disease is caused by another rickettsial bacterium, Rickettsia africae. Fever and rash follow a tick bite. Unlike Mediterranean spotted fever:
- Multiple eschars may be present
- The rash is vesicular
- May be present in only 30% of patients
- Doxycycline 100 mg twice daily x 3 to 5 days
- Chloramphenicol 500 mg four times daily x 3 to 5 days
Take measures to prevent tick bites, especially if engaging in outdoor activities in rural areas. Tick-bite prevention measures include applying a DEET- or picaridin-containing repellent to exposed skin and permethrin spray or solution to clothing and gear. There is no vaccine against this disease.
This is an acute bacterial infection that can be transmitted to humans by ticks or lice. The cause is a spirochete (Borrelia recurrentis). Tick-borne relapsing fever is found in Asia, Africa, Europe, and the Americas, including mountainous areas of the western United States. Louse-borne relapsing fever, seen almost exclusively among the poor or those in refugee camps, is found in Asia, Africa, and Europe.
Ehrlichiosis & anaplasmosis
These diseases are caused by bacteria transmitted by ticks. Two types of human infections are recognized in the United States. The infections have the same symptoms and the same treatment but differ in their geographic distribution because of the fact they are transmitted by different species of ticks.
- Human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, is transmitted by Lone Star ticks (Amblyomma americanum). These ticks are found predominantly in the Southeast and Mid-Atlantic states.
- Human granulocytic anaplasmosis (HGA), previously known as human granulocytic ehrlichiosis (HGE), is a tick-associated disease caused by a species of bacteria called Anaplasma phagocytophilum. HGA is transmistted to humans by the bite of the deer tick and western black-legged tick. Deer ticks infected with A. phagocytophilum are found in the New England and North Central United States while black-legged ticks infected with A. phagocytophilum are found in northern California. States reporting the highest incidence of HGA in 2001-2002 were Rhode Island, Minnesota, Connecticut, New York, and Maryland. Overseas, cases of HGA have been documented in many countries in Europe, as well as Argentina, Japan, Malaysia, and Venezuela.
Symptoms of the two infections are practically identical. Most patients have a nonspecific flulike illness with chills, fever, headache, muscle aches, and malaise. In 15% of the cases, however, the disease is more severe and patients can develop kidney failure, pneumonia, and neurologic changes such as seizures and coma. The fatality rate is 2% to 5%.
Suspect the diagnosis in anybody with a febrile illness (with the symptoms above) who has a low white blood cell count (leukopenia), low platelet count (throbocytopenia) and abnormal liver function tests, and who has been in an endemic area, especially between April and September. The white blood cells of some patients will have characteristic inclusion bodies in their white blood cells. Antibody tests may be used to establish a diagnosis.
When a case of ehrlichiosis or anaplasmosis is suspected, treatment should be started immediately. The drug of choice is doxycycline, 100 mg twice daily, for 10 to 14 days.
This is a tick-borne illness that can be prevented by insect bite prevention measures, as outlined in Chapter 8.
Other Tick-Borne Diseases in the United States
Lyme disease (Chapter 11) and ehrlichiosis are not the only illnesses transmitted by ticks in the United States. Rocky Mountain spotted fever, Colorado tick fever, tick paralysis, tularemia, babesiosis, and relapsing fever are some of the other diseases of importance. A summary of the tick vectors that spread these diseases and their geographic distribution follows subsequently.
IMPORTANT TICKS AND TICK-BORNE DISEASES IN THE UNITED STATES
The deer tick (Ixodes scapularis) is found in great abundance from Virginia to Maine, as well as in Wisconsin and Minnesota, whereas its first cousin, the western deer tick (Ixodes pacificus, the black-legged tick) is active along the West Coast. The deer tick is a very small tick, much smaller than the dog tick or wood tick. Deer ticks, both adults and nymphs, are dark reddish brown and have black legs and a pear-shaped body. All stages, especially nymphs and adults, feed on people. The deer tick is the most important carrier of Lyme disease and is the only known carrier of babesiosis. It is also the primary transmitter of human granulocytic anaplasmosis.
The Lone Star tick (Amblyomma americanum) is found throughout the south and southeastern United States, with a high density in the Ozarks. Adults are about one-quarter inch long; nymphs, which are the most aggressive biters, are pinhead sized. The ticks are reddish brown, and the female has a white mark on the middle of her back. The smaller male has lacy white markings on the rear edge of his back. Lone Star ticks transmit monocytic ehrlichiosis, tularemia, and a variant form of Lyme disease, Southern tick-associated rash illness (STARI).
The American dog tick (Dermacentor variabilis) is widely distributed in the eastern half of the United States and is also found on the West Coast. It resembles the wood tick in appearance. The unfed female has silvery-gray markings on the shield on her back; the rest of the body is reddish brown. It is bigger than other ticks—approximately one-eighth inch to one-quarter inch long—and although it prefers dogs, it does bite people. The dog tick is the most important transmitter of Rocky Mountain spotted fever. It also transmits tularemia and probably transmits human granulocytic anaplasmosis. The dog tick can cause tick paralysis.
The Rocky Mountain wood tick (Dermacentor andersoni) is a hard tick that resembles the American dog tick and the Pacific coast tick. The female has silvery-gray markings on the shield on her back; the rest is reddish brown. This tick is the prime carrier of Rocky Mountain spotted fever in the West, and it also transmits tularemia and Colorado tick fever (mountain fever). It is the most important cause of tick paralysis in the United States.
Relapsing fever ticks (Ornithodoros hermsi, O. parkeri, O. talaje, O. turicata) are soft ticks that transmit relapsing fever, a spirochetal disease. Their bites can be painful. Relapsing fever ticks are widely scattered west of the Mississippi River. Adults are oval-shaped and colored gray to pale blue. Larvae and nymphs are gray.
The brown dog tick (Rhipicephalus sanguineus) is found throughout the United States wherever you find dogs. Although suspected of carrying ehrlichiosis, these ticks are probably not disease transmitters. The male is uniformly dark brown. The female is brown but the shield on her back is darker than the rest of her body.