Tropical Diseases

Some of the organisms that cause tropical diseases are bacteria and viruses, terms that may be familiar to most people since these types of organisms cause illness common in the U.S.

Less well known are those more complex organisms commonly referred to as parasites. All of these types of agents may be referred to generically as pathogens -- meaning any organisms that cause disease.

In the temperate climate zones, many familiar viral and bacterial diseases are spread directly from person to person, by airborne routes of transmission or by sexual contact. In the tropics, respiratory diseases (such as measles, respiratory syncytial virus, tuberculosis) and sexually transmitted diseases are also of great importance.

In addition, many diseases are spread by contaminated water and food sources, since clean water and sanitary conditions are often a luxury in developing countries.

Alternatively, some tropical disease agents are transmitted by an intermediate carrier or vector. The insect or other invertebrate vector picks up the pathogen from an infected person or animal and transmits it to others in the process of feeding. Often, tropical disease agents must undergo important developmental changes within the vector before they complete their life cycle and once again become infective for man.

Viruses
Viruses are minute infectious agents that generally consist only of genetic material covered by a protein shell. They only replicate within cells, which provide the synthetic machinery necessary to produce new virus particles.

Arboviruses (ar'bow)
The term "arboviruses" is short for "arthropod-borne viruses". Arthropods include many of the medically important bugs (mosquitoes, ticks, flies, etc.) that may transmit pathogens to humans. Arboviruses are of special relevance as tropical diseases.

Dengue (deng'ee) fever, caused by a mosquito-borne flavivirus, is found in tropical and subtropical regions of the Americas, Africa, Asia and Australia. In its acute form, dengue is characterized by flu-like symptoms including severe pain in the head, eyes, muscles and joints.

Some patients, particularly infants and children, develop "dengue hemorrhagic fever", a severe and sometimes fatal variation involving circulatory failure and shock.

The incidence of both forms of dengue infection has recently been increasing, as expanding urbanization enlarges the regions inhabited by the Aedes mosquito vector. Mosquitoes capable of transmitting this disease are also found within the United States.

Yellow fever is another arboviral disease, characterized by fever, hemorrhage, and often fatal liver complications. It is limited to tropical South America and Africa, where it is sometimes epidemic in spite of the existence of a safe and effective vaccine. The potential for increased incidence of yellow fever appears to be growing with the expanding distribution of the vector Aedes mosquitoes.

Rotavirus (row'ta)
Rotavirus causes watery diarrhea and vomiting, primarily in young children. These viruses are distributed worldwide and transmission is usually due to contact with infected individuals or fecally contaminated objects. The majority of infections are self-limiting, but infant mortality is higher in developing countries and is generally associated with severe dehydration. As with cholera, treatment consists of replacing lost fluids and electrolytes.

AIDS
The human immunodeficiency viruses (HIV) associated with the Acquired Immunodeficiency Syndrome (AIDS) have become widespread in developing nations.

By 1996, over 13 million adults were living with HIV in sub-Saharan Africa, representing about 60% of the global number of infected individuals. The spread of HIV in this region has been exacerbated by recent crises, such as natural disasters and armed conflict, with resulting mass population movements.

The number of infected individuals in Asia is also rapidly rising; it is currently estimated that over 5 million people are living with HIV/AIDS in South and Southeast Asia.

The progressive erosion of the immune system suffered by HIV-infected individuals renders them more susceptible to other infections. Often these secondary (or "opportunistic") infections are atypical or more severe than they would appear in an immunocompetent person.

Since different diseases are prominent in tropical regions, patterns of the HIV-associated infections may diverge significantly from those seen in the developed nations. Moreover, it is thought that being infected with one or more tropical diseases may affect the course of AIDS upon subsequent HIV infection.

Ebola (ee-bow'lah)
Ebola virus causes fever, severe headache, backache, vomiting, diarrhea, and severe hemorrhaging. The method by which Ebola is transmitted in nature, and what animal is its natural host, remains unclear.

In recent outbreaks such as those that have occurred in Zaire, Sudan and Gabon, man's initial contact with the virus has clearly been accidental. When humans acquire the infection, however, it spreads rapidly to those in contact with body fluids from the patient and the mortality rate is very high.

Marburg virus is related to Ebola, but usually has a somewhat lower mortality rate.

Lassa fever (lah'sah) Lassa is another often fatal hemorrhagic fever virus. It is transmitted by rodents. Symptoms of Lassa fever include sharp backache and/or headache, sore throat, fever, rashes, dehydration, general swelling, skin hemorrhaging, irregular heart beat, and disorientation.

Viruses causing several types of South American hemorrhagic fevers belong to the arenavirus family like Lassa, and are also carried by rodents.

Bacteria
Bacteria (singular = bacterium) are more complex than viruses, containing genetic information and much of the equipment necessary to produce energy and replicate independently. Some bacteria, however, can only reproduce when growing inside a cell, from which they derive required nutrients

Cholera (kol' er-ah)
Cholera is a diarrheal disease caused by infection with Vibrio cholerae, a bacterium most often found in contaminated water and shellfish, which produces a toxin that upsets the biochemical balance of cells lining the intestine and makes them secrete copious amounts of water and electrolytes.

Cholera is endemic in a number of tropical countries, and periodically major epidemics break out such as that affecting some 900,000 persons in South America between 1991 and 1993.

Cholera is characterized by severe watery diarrhea which, if left untreated, can result in serious dehydration and death. Treatment consists of replacement of lost water, salts and sugar.

Escherichia coli (esh-er-i'kee-a koh'lye)
Escherichia coli bacteria, more widely known as E. coli, can produce toxins similar to those of the cholera bacteria, causing illness ranging from traveler's diarrhea to persistent diarrhea with associated malnutrition.

An extremely pathogenic form of these bacteria causes bloody diarrhea and kidney complications, such as recently observed in outbreaks in the U.S., Japan, and Scotland, which can be lethal - particularly in children and the elderly. This form, sometimes known as 0157:H7 or EHEC (enterohemorrhagic E. coli) is often associated with ingestion of undercooked meat, but has also been found in other foods, including unpasteurized milk and fruit juices.

Tuberculosis (tu-ber-ku-loh'sis)
Caused primarily by the bacterium Mycobacterium tuberculosis (my-koh-bak-teer'ee-uhm), this is an infection that can last a lifetime, resulting in disease to virtually every organ in the body but primarily affecting the lungs. Tuberculosis occurs all over the world.

Until recently, it was thought to be well controlled in the more developed countries; unfortunately, however, it is again on the increase due to its association as an opportunistic infection of AIDS and its prevalence in drug-abusers. Tuberculosis remains a major problem in the developing world, where conditions of poverty, poor nutrition and crowding contribute to its prevalence.

It has been estimated that 5 to 15% of infected individuals develop disease. Pulmonary tuberculosis is the most common manifestation worldwide, and is associated with fatigue, weight loss, coughing and difficulty in breathing. Several drugs are available, but drawbacks include the need for lengthy treatment and increasing development of drug resistance by the bacteria.

Hansen's disease
Hansen's disease, also known as leprosy, is caused by the bacterium, Mycobacterium leprae, which is related to the agent that causes tuberculosis.

There are 3.7 million cases officially registered, but the actual number of infected individuals is at least two to three times higher. The exact mechanism of transmission from person to person remains unknown, but likely involves contact with infected skin or nasal secretions.

The bacteria grow mainly in tissue cells known as macrophages (literally "big eaters", these cells are important components of the immune system) in the skin and in Schwann cells surrounding nerves. As in the case of some of the parasitic diseases, the body's reaction to the leprosy bacillus is responsible for disease.

The clinical course of leprosy is extremely variable. Some infected individuals may remain without symptoms. In its worst form, bacterial growth is uncontrolled, leading to loss of sensation in the affected area, which may predispose to trauma and consequent deformity.

Presently, no methods for prevention exist. Treatment relies on long-term administration of antibiotics. Difficulties are encountered due to the development of drug resistance and the failure of patients to comply with treatment regimens.

Parasites
Parasites are organisms that live within or on another organism, the host, at whose expense they obtain some advantage such as nourishment. This group of pathogens includes the protozoa (single-celled organisms more complex than bacteria) and the helminths(multicellular organisms commonly referred to as worms).

Thus, parasites can range all the way from microscopic protozoa up to worms that reach three feet long. The environment in which parasites can live is spectacularly diverse: different types of protozoa may set up housekeeping in red blood cells, white blood cells (including those that are normally responsible for killing intruding microorganisms), muscle cells, brain cells, heart cells, liver cells and others, or they may live extracellularly in such sites as the blood, tissues or mucosal secretions.

Incredibly, some types of worms may also live within cells, but for the most part they live extracellularly within the gut, the blood, the lymphatics, or tissues of the skin, eyes and elsewhere.

As opposed to bacteria and viruses, many types of parasites undergo complex developmental transformations, involving growth within both mammalian and invertebrate hosts as well as both sexual and asexual types of reproduction, during their complicated life cycles.

Malaria (mah-lair'ee-ah)
Over 300 million people develop clinical cases of malaria each year, and one to three million of them die. Many of these are children living in subsaharan Africa.

Almost half of the world's population lives in an area where they are at risk of contracting the disease. Malaria is caused by protozoa of genus Plasmodium. Each of the four species of malaria parasite that infect man causes a somewhat different form of the disease.

Malaria caused by P. falciparum is the most dangerous form and accounts for the overwhelming majority of deaths. Unless appropriately treated, it can produce several life-threatening complications including kidney failure and coma.

The parasites are transmitted to humans by female anopheline mosquitoes. When the mosquito takes a blood meal on the host, she injects the parasites along with her saliva. The parasites develop first in liver cells and then infect red blood cells (erythrocytes), where they consume hemoglobin, the oxygen-carrying component of the blood.

The parasites divide in the red cell, and at the completion of development the red cell ruptures releasing parasites that can infect many other erythrocytes. The typical symptoms of malaria, cycles of chills, fever and sweating, are experienced by patients at these times.

In 1955, the World Health Organization began an extensive campaign, using insecticides and drugs, to eradicate malaria. Despite a number of dramatic successes, the objective proved elusive. Mosquitoes not only modified their behavior to avoid coming into contact with insecticides, but actually developed resistance to these chemicals.

Parasites also became resistant to the widely used drug chloroquine and other antimalarials. Mounting evidence shows that malaria is once again gaining the upper hand. Areas that have been free of malaria have been experiencing outbreaks, and the number of cases has been rising alarmingly in the Amazon and parts of Asia, especially Southeast Asia. In Africa, malaria has been moving from rural areas to the cities.

At one time, malaria was a serious health problem in the U.S.; in 1914 more than 600,000 cases of malaria occurred here. Although improved public health led to a substantial decline in the following decades, minor resurgences have occurred as troops returned from both the Korean and Vietnam wars.

In 1995, approximately 1,200 cases of malaria were reported to the U.S. Centers for Disease Control and Prevention. Not all of these cases of "imported" (acquired outside the U.S.); several were recent infections acquired within the U.S. following the bite of indigenous mosquitoes.

More recently, cases of locally transmitted malaria have been appearing in regions as diverse as California, Florida, New Jersey, New York, Texas and Michigan.

Leishmaniasis (leesh-mah-nye'ah-sis)
Leishmaniasis is actually a group of diseases, caused by infection with protozoa belonging to the genus Leishmania. There are about 20 different species that are transmitted to man by the bite of infected female sandflies. In the mammalian host, the parasite is found within macrophages. These cells are usually responsible for destroying invading microorganisms, and the remarkable ability of leishmanial parasites to evade their anti-microbial mechanisms has attracted considerable scientific interest.

Like malaria, leishmaniasis is widely distributed over large portions of the tropical and subtropical areas of the world, including portions of southern Europe. Cases have been anecdotally reported in the Southwestern U.S.

The World Health Organization reports 12 million infected individuals with 300 million people at risk in some 80 countries. Reservoir hosts, such as dogs and rodents, play an important role in the distribution of the infection.

People contract leishmaniasis when their activities bring them into close association with sandflies; for example, workers in the forests of South America are frequently exposed.

Leishmaniasis takes many forms, depending on both host and parasite factors. Symptoms may range from self-healing skin ulcers to severe life threatening disease. Cutaneous leishmaniasis, known locally by various names such as Baghdad ulcer, Delhi boil or oriental sore, is manifested by skin lesions that usually resolve but may leave ugly scars.

In some individuals, the disease spreads to the mucous membranes of the nose and mouth, resulting in hideous destruction of facial features. The most dangerous form is visceral leishmaniasis, where parasites invade the internal organs. This disease is commonly referred to as kala-azar, a Hindi term for "black-sickness" which describes the increased pigmentation of the skin. Symptoms include fever and weight loss. If left untreated, kala-azar invariably leads to death. Recent leishmaniasis epidemics in Sudan and India have highlighted the problem.

Trypanosomiasis (tri-pan-o-so-mye'ah-sis)
The protozoa causing trypanosomiasis are closely related to leishmania parasites. In humans, different species of the genus Trypanosoma are responsible for diseases that are quite distinct in clinical outcome and in geographic distribution.

The New World form, Chagas' disease or American trypanosomiasis, caused by Trypanosoma cruzi, affects about 18 million people living mostly in Latin America. The parasite is transmitted to man by blood-sucking reduviid bugs, also known as kissing bugs due to their predilection for feeding on the faces of their victims.

Unlike malaria and leishmaniasis, the parasites are not injected during feeding; rather they are deposited by defecating bugs. The parasite enters the host through the eyes, nose or mouth, or through breaks in the skin. Symptoms may appear as acute disease shortly after infection or as chronic disease years later.

Acute disease involves fever, swelling of the lymph nodes and, sometimes, inflammation of the heart muscle and of the brain. Although the acute stage may be fatal, especially in children, most infected individuals survive and enter a long symptom-less stage.

One quarter or more will develop cardiac damage that may result in heart failure and sudden death; others may develop digestive disorders.

Trypanosoma cruzi infection is not limited to humans and the presence of other infected mammals is sufficient to sustain the infection in nature. Control measures rely on limiting contact with infected bugs, because prophylaxis and drug treatment are not effective. Vector control methods involve insecticide spraying and eliminating the breeding grounds of the bugs.

The trypanosomes responsible for human disease in Africa, African trypanosomiasis or "sleeping sickness", are different from those causing Chagas' disease. This disease affects some 25,000 people per year; however, epidemics involving many times that number are well-known.

These parasites are very closely related to trypanosomes that produce veterinary disease and prevent development of ranch lands in Africa, thereby depriving people of an important source of food. These trypanosomes are transmitted to man by the bite of tsetse flies.

Initial symptoms include fever, headache, dizziness and weakness. Later, parasites invade the central nervous system, causing neurological and psychological problems, including hallucinations, delusions and seizures. Untreated, the patient may become comatose and die.  

A feature of parasite biology that has long intrigued scientists is the ability of these organisms to evade the immune response by a process known as "antigenic variation".

By means of a complex genetic mechanism, which is currently being unraveled, the parasite is able to repeatedly change the protein that covers its entire surface, thereby staying one step ahead of the ability of the host immune system to recognize and react to it. The inability of the host to recognize these new variants allows the parasite to survive for long periods of time.

Schistosomiasis (shis-toh-soh-my'uh-sis)
This disease is caused by several species of flatworms of the genus Schistosoma. About 200 million people are infected, with three times that many at risk. An estimated 200,000 people (0.1% of those infected) die every year, but many more (about 10% of infected individuals) suffer chronic damage to vital organs including the liver and kidney.

Interestingly, while this parasite's life cycle also involves an invertebrate vector, it is not transmitted through the bite of an insect, but rather develops within freshwater snails. After exiting from the snail vector, schistosome larvae swim along until they contact a human host bathing or working in the water.

They penetrate the skin, and subsequently migrate through the blood vessels until finally establishing residence in veins of the intestines or urinary bladder, depending on the parasite species. The adult male and female worms pair, mate and produce large numbers of eggs, some of which are excreted in either feces or urine and wind up in the water supply where they hatch and complete the cycle by infecting new snail hosts.

The adult worms do not cause the most common manifestations of the disease. Those eggs that are not excreted but instead become lodged in the body's tissues cause disease.

In a process known as granuloma formation, masses of cells form around the eggs in an effort to destroy them; in so doing, however, these cells initiate a process of tissue scarring (fibrosis). In those forms of the disease involving the liver and intestines, this impedes blood circulation and can cause death due to rupture of distended blood vessels. In the form involving the bladder, the extensive scarring can result in obstruction of urinary outflow.

Filariasis (fil-ah-rye ' ah-sis)
Filarial diseases are rarely life threatening or acute; they are, however, extremely debilitating and disfiguring, and make affected individuals dependent on others or on limited health care resources.

These roundworms are related to the dog heartworm, which is well known to pet lovers in the temperate zones. Transmitted to man by the bite of infected mosquitoes, filarial worms of the genera Wuchereria and Brugia cause lymphatic filariasis.

One billion people live in areas where filariasis is found, and approximately 90 million people are estimated to have the disease. When the infected female mosquito feeds on humans, she injects larval stages of the parasite. These larvae migrate through the tissues, and develop into adults that take up residence in the lymphatic system.

Disease results from extensive obstruction and damage to the lymphatic system. The end result is frequently a build up of lymph fluid in the limbs, and sometimes scrotal sac, which may cause the grotesque swelling known as elephantiasis, hanging groin and hydrocele. Male and female worms mate to produce millions of progeny called microfilariae, which end up in the blood and serve to transmit the parasite back to the insect vector.

The form of filariasis known as onchocerciasis or "river blindness", caused by Onchocerca volvulus, is transmitted by a group of insects known as blackflies, which breed in fast moving rivers and streams.

Some 90 million people are at risk in 36 countries, mostly in Africa and South America, and 18 million people are infected. The adult forms of O. volvulus live under the skin, forming visible nodules.

Most of the symptoms of the disease result from the migration of the larval stages (microfilariae) into the skin and eyes. Reaction to these stages leads to intense itching and disfiguring dermatitis as well as damage to the eyes, including corneal scarring. Onchocerciasis is a frequent cause of blindness in the tropics, affecting well over 300,000 people.

Disease control in West Africa has been brought about by the Onchocerciasis Control Programme, which coordinates the regular release of insecticides into the rivers and streams of 11 countries in this region. The program is designed to eliminate the larval stages of the blackfly vector. Ivermectin (Mectizan®), a drug originally developed for veterinary use, has proven to be an effective treatment. Merck, Sharp and Dohme, the manufacturers, have provided the compound free to all countries with endemic onchocerciasis.

Enteric Protozoa
Two parasitic infections that have recently come to widespread public attention in the U.S. are Cryptosporidium parvum (krip-toh-spoh-rid'ee-uhm) and Cyclospora cayetanensis (sye-kloh-spoh'rah).

These protozoan parasites cause persistent diarrhea, and are usually acquired by ingestion of contaminated water or food. Travelers to tropical countries may be at increased risk for acquiring these infections, but more and more cases are being recognized in countries such as the U.S. and Canada.

The first outbreak of cryptosporidiosis in a child-care center was observed in 1983. In 1993, an outbreak associated with contaminated drinking water occurred in Milwaukee, Wisconsin, that affected some 403,000 people.

Cryptosporidiosis causes especially severe diarrhea in AIDS patients. It has been estimated that 10-15% of the chronic diarrhea and wasting observed in AIDS patients in the U.S. is due to this infection, while it may account for as much as 30-50% of severe diarrhea in AIDS patients in developing countries. There is still no adequate treatment of cryptosporidiosis.

Although probably discovered around the turn of the century, Cyclospora cayatenensis was actually characterized and named in the course of ongoing studies in Peru. Like cryptosporidiosis, our understanding of cyclospora infection has been influenced by the AIDS epidemic and subsequent improvements in diagnosis.

It appears that globally, Cyclospora affects approximately equivalent numbers of immunocompetent and immunosuppressed individuals. The emergence of this parasite as a problem in developed countries became widely recognized in the summer of 1996, when over 1500 cases were reported from some 14 U.S. states and Canada as a result of eating contaminated berries.

Another water-borne protozoan, Giardia lamblia (gee-ar'dee-ah), which causes diarrheal disease, is also endemic in the U.S. It has become recognized as one of the most common causes of waterborne disease in humans in the U.S., and is also found throughout the world.

Diarrhea, abdominal cramps, and nausea are the most common symptoms of giardiasis. These may lead to weight loss and dehydration. Persons at increased risk for giardiasis include child care workers, diaper-aged children who attend day-care centers, international travellers, and hikers or campers who drink untreated water from contaminated sources.

The protozoan Entamoeba histolytica (en-tah-mee'bah), which causes severe dysentery and liver disease, is estimated to kill up to 100,000 people annually. This parasite is found throughout the world, although it is especially problematic in underdeveloped tropical and subtropical regions. The main source of transmission is people who carry a chronic infection; feces infected with the cyst form of the parasite may contaminate fresh food or water.

Other Protozoa
Toxoplasma gondii (toks-oh-plaz'mah) is a protozoan parasite common in the U.S. and other developed countries. It is estimated that more than 60 million people in the U.S. carry the toxoplasma parasite, which is transmitted in the feces of infected cats or can be acquired by eating undercooked meat.

Ordinarily T. gondii infection is benign, because the immune system keeps the parasite from causing illness. In most cases, it can be mistaken for the "flu", causing swollen lymph nodes or muscle aches. But it can cause serious neurological disorders in immunocompromised people, or in the fetus if first acquired by a mother during pregnancy.

Trichomonas vaginalis (trih-koh-moh'nas) a sexually transmitted protozoan parasite, which causes vaginal and urinary tract inflammation and, in women, has been associated with adverse outcomes of pregnancy.

Other Helminth Parasites
It is estimated that at least one quarter of the world's population is infected with parasitic worms. Many people living in tropical regions, where famine and malnutrition already create health problems, are infected with more than one of these helminth parasites.

These parasites further rob their human hosts of blood and nutrients; it is easy to understand how they can affect the physical and mental development of children and the ability of adults to work.

Hookworm infections occur mostly in tropical and subtropical climates. One type of hookworm, Necator americanus (neh-kay'tor), was widespread in the southestern U.S. early in this century.

Hookworm infection usually causes mild diarrhea or cramps. However, heavy infection with these bloodsucking intestinal roundworms can cause profound anemia, resulting in growth and mental retardation in children.

People generally acquire hookworm infection by direct contact with contaminated soil, for example, by walking barefoot. When eggs passed in the feces reach the soil, they hatch and develop into infective larvae that can penetrate the skin. Children, because they play in dirt and often go barefoot, are at particularly high risk for infection.

Ascaris (as-kar'is) worms are found in temperate as well as tropical regions; indeed they are probably the most common parasite in the world. While the mortality rate is relatively low (estimated at 20,000 per year), ascaris infection can be debilitating, causing abdominal pain and lack of weight gain in children and sometimes resulting in intestinal obstruction.

Other intestinal roundworms are also prevalent in the developing world. Trichuris (trik-u'ris) worms afflict approximately 750 million people, and can cause severe anemia, abdominal pain, nausea and weight loss. Strongyloides (stron-ji-loi'deez) worms infect around 80 million people, and cause abdominal pain, nausea and diarrhea.

Another type of helminth parasite, the tapeworm Taenia solium (te'ne-yah), also causes serious human disease. Pigs and humans are affected by this tapeworm.

Generally, people acquire an active infection by eating undercooked pork containing the larval form of the parasite. The ingested larvae then develop into adult, egg-laying, worms in the person's intestine. Eggs pass out of the body in the feces, and are spread to the environment where they may be ingested by pigs, to continue this life cycle, or by other humans.

When eggs are inadvertently eaten by people, the larvae may infect the central nervous system and brain, causing serious neurologic disorders, including seizures. This disease, called neurocysticercosis (nu-row-sis-te-sir-ko'sis) after the name of the larval stage, is a serious problem in rural parts of Latin America. It may be also be emerging in the U.S.

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