African Sleeping Sickness (Trypanosomiasis)

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African Sleeping Sickness (Trypanosomiasis)

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Trypanosomiasis (tri-PAN-o-SO-my-a-sis), which is also known as African sleeping sickness because of the semi-conscious stupor and excessive sleep that can occur in someone who is infected, is an infection passed to humans through the bite of the tsetse fly. Thus, it is a vector-borne disease. The fly bite transfers either Trypanosoma brucei rhodesiense, which causes a version of the disease called East African trypanosomiasis, or T. brucei gambiense, which causes West African trypanosomiasis. If left untreated, trypanosomiasis is ultimately fatal.

Trypanosomiasis is common in Africa. In the 1960s the disease was almost eradicated, but interruptions in the delivery of public health to affected regions due to government indifference and warfare caused a re-emergence of the disease, now resulting in tens of thousands of cases every year. The World Health Organization (WHO) estimates that in 2005 there were 50,000–70,000 new cases. This is a drop from higher numbers reported during the 1990s. An ongoing effort involving WHO, Médecines Sans Frontières (Doctors Without Borders), and several pharmaceutical companies is again attempting to bring trypanosomiasis under control.

Disease History, Characteristics, and Transmission

Trypanosomiasis has been known for centuries. It was first described in the fourteenth century in the land-locked region of northwestern Africa that today is known as Mali. The involvement of the trypanosomes and the tsetse fly were discovered by Sir David Bruce in 1902-1903. A few years later, a massive epidemic that affected millions of Africans and killed 500,000 people called attention to the seriousness of the disease. Shortly afterward, the association between trypanosomiasis and the tsetse fly was established.

T. brucei rhodesiense and T. brucei gambiense are protozoa. Protozoans are single-celled organisms that are more complex in structure than bacteria and viruses; the organisms are considered to be animals. The protozoa responsible for sleeping sickness are native to Africa. The few cases of trypanosomiasis that occur outside of Africa each year generally result from travelers who acquire the protozoa in Africa, then leave and subsequently develop the disease in another country.

The two protozoans have a complex life cycle. In the animal host, the organisms that are injected by a tsetse fly progressively change their shape to what is described as the stumpy form. This form is able to infect a tsetse fly when it takes a blood meal from an animal. While inside the gut of the fly, the protozoans change again into a form that is able to migrate to the salivary glands of the fly. Finally, another change in the organism occurs; the protozoan is now capable of infecting another animal when the tsetse fly seeks a blood meal. This animal-to-human cycle can continue until the chain of transmission (also called the cycle of infection) is interrupted, usually by an organized effort by agencies such as WHO.

T. brucei rhodesiense is naturally carried by antelopes. The antelopes are not harmed by the protozoan and serve as the natural reservoir of the T. brucei rhodesiense. Tsetse flies who obtain a blood meal from an antelope can acquire the protozoan, which they can transfer to humans or cows. The resulting infection is lethal in cattle. People who are most likely to become infected are those who come into contact with cattle or antelopes. Thus, those who raise cattle, or the game wardens and visitors to East African game reserves and other rural areas are at risk.

T. brucei gambiense does not infect antelope or cattle. It resides in creatures that live in the tropical rain forests found in Central and West Africa. The disease caused by this protozoan in humans produces more severe symptoms and more often results in death. Fortunately, because of its isolated distribution, fewer people contract this form of trypanosomiasis.

The infection due to T. brucei rhodesiense progresses more swiftly than the longer-lasting infection that is caused by T. brucei gambiense. Both infections inevitably lead to death if they are not treated.

Sleeping sickness is a complex disease, with interactions between humans, the tsetse fly vector, and the animal host. This can complicate efforts to control the disease.

Typically, the first indication of both types of trypanosomiasis is the development of redness, pain, and swelling at the site of the fly bite several days after having been bitten. The sore is also referred to as a chancre. Some people also develop a rash. Both forms of the disease then progress in two stages. The first stage begins two to three weeks following the bite and the entry of the protozoans into the bloodstream. The symptoms of this stage develop as the trypanosome is carried throughout the body in the bloodstream. The lymphatic system, which is an important part of the immune system, can also become infected. Because at this stage the disease affects the whole body, it is termed the systemic phase. A hallmark of the illness at this point is an extreme fluctuation of body temperature. A person's temperature will cycle from normal to very high and back again, which is a consequence of the immune system's reaction to the protozoan. Additionally, a person may experience a feeling of extreme itchiness and develop a headache. Some people become mentally disoriented. If left untreated, a person can lapse into a coma and die.

West African trypanosomiasis also produces marked swelling of lymph nodes, especially those located behind the ear and at the base of the neck, and swelling of both the spleen and the liver. East African trypanosomiasis can cause the heart to become inflamed and to malfunction.

Some of the symptoms of trypanosomiasis that can occur during the first stage of the illness are a result of the immune reaction to the infection. The immune response remains strong, since invading trypanosomes can shift the composition of their outer surface. As the immune system hones in on one surface configuration, that configuration can rapidly change. This trait is known as antigenic variation. The trypanosomes are capable of expressing thousands of different surface profiles during the years that an infection can last. A consequence of the heightened immune response due to the changing surface of the protozoan is the cycling fever, as well as organ damage and weakened blood vessels; the latter aid in the spread of the organism throughout the body.

The second stage of trypanosomiasis involves the nervous system. As the brain becomes affected, a person can experience difficulties in speaking, mental disorientation, and periods of near-unconsciousness or sleep during the daytime (hence the term sleeping sickness). During the night, insomnia robs a person of sleep. Other symptoms can develop that mimic those of Parkinson's disease; these include difficulty in movement, with difficulty in walking that can require a shuffling motion to avoid falling down, involuntary movement or trembling of arms and legs, and a tightening of muscles. With more time, a person can lapse into a coma and die.

Trypanosomiasis can also be transferred from a pregnant woman to her baby prior to birth or via transfusion with infected blood or a contaminated organ that is transplanted. However, these routes of infection are rare.

Scope and Distribution

Trypanosomiasis is prevalent in regions of Africa. East African trypanosomiasis is found in Uganda, Tanzania, Kenya, Malawi, Zaire, Ethiopia, Botswana, and Zimbabwe. West African trypanosomiasis is prevalent in Western and Central Africa.

According to the WHO, in 2002 trypanosomiasis was constantly present in 11 countries and almost as prevalent in a further 12 countries. As of 2007, epidemics are occurring in the Democratic Republic of Congo, Angola, and Sudan.

Spread of the disease to humans occurs only in Africa, since the tsetse fly is only found on the African continent. On the rare occasions that trypanosomiasis occurs elsewhere in the world, it is usually the result of travel by someone who became infected while in Africa. As of February 2006, the United States Centers for Disease Control and Prevention (CDC) has records of only 36 cases of the disease in the United States, and all involved people who contracted the disease in Africa.

A version of trypanosomiasis called Chagas disease, which is caused by Trypanosoma cruzi, occurs in South America and sometimes in Central and North America.

The WHO estimates that there are 50,000 or more cases of East and West African trypanosomias every year. However, since the majority of cases occur in regions of Africa where organized medical care and reporting is scant, the actual number of cases is likely much higher. The CDC estimates that there are over 100,000 new cases every year.

Treatment and Prevention

The diagnosis of trypanosomiasis involves examination of the fluid from either the site of the tsetse fly bite or from a swollen lymph node or blood, to detect the presence of infecting protozoa. As well, fluid can be injected into rats, which can develop an infection. Blood recovered from the rats after several weeks will contain the protozoa.

WORDS TO KNOW

CHAIN OF TRANSMISSION: Chain of transmission refers to the route by which an infection is spread from its source to susceptible host. An example of a chain of transmission is the spread of malaria from an infected animal to humans via mosquitoes.

EPIDEMIC: From the Greek epidemic, meaning “prevalent among the people,” is most commonly used to describe an outbreak of an illness or disease in which the number of individual cases significantly exceeds the usual or expected number of cases in any given population.

PROTOZOA: Single-celled animal-like microscopic organisms that live by taking in food rather than making it by photosynthesis and must live in the presence of water. (Singular: protozoan.) Protozoa are a diverse group of single-celled organisms, with more than 50,000 different types represented. The vast majority are microscopic, many measuring less than 5 one-thousandth of an inch (or 0.005 millimeters), but some, such as the freshwater Spirostomun, may reach 0.17 inches (3 millimeters) in length, large enough to enable it to be seen with the naked eye.

RE-EMERGING INFECTIOUS DISEASE: Re-emerging infectious diseases are illnesses such as malaria, diphtheria, tuberculosis, and polio that were once nearly absent from the world but are starting to cause greater numbers of infections once again. These illnesses are reappearing for many reasons. Malaria and other mosquito-borne illnesses increase when mosquito-control measures decrease. Other diseases are spreading because people have stopped being vaccinated, as happened with diphtheria after the collapse of the Soviet Union. A few diseases are reemerging because drugs to treat them have become less available or drug-resistant strains have developed.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

VECTOR: Any agent, living or otherwise, that carries and transmits parasites and diseases. Also, an organism or chemical used to transport a gene into a new host cell.

Medications are available to treat trypanosomiasis. A drug called pentamidine is used for the early stage of T. brucei gambiense infections, and the drug suramin is used for the early stage of infections caused by T. brucie rhodesiense. More advanced stages of both forms of the disease are treated using a drug called melarsoprol. Those who do not respond to melarsoprol can be given another drug called eflornithine. Unfortunately, the drugs can have undesirable side effects. For example, suramin, eflornithine, and pentamidine can cause a fatal reaction in the kidney or liver, or inflammation in the brain. These drugs must be used with care and their effects monitored; they are usually only used in a hospital setting. While these drugs can be effective, the CDC does not recommend any particular medication.

Trypanosomiasis cannot clear up on its own. Hospitalization and treatment is necessary. Those who recover from the infection should be monitored for several years afterward to ensure that the infection does not recur.

As of 2007, there is no vaccine for either form of trypanosomiasis. Prevention of the disease consists of avoiding contact with the tsetse fly. For example, contact with bushes should be minimized, as the flies often rest there. Bushes and other shrubbery that are near rivers or waterholes are prime spots for tsetse flies, and so should be avoided. This habitat tends to be rural, so people who spend time traveling or staying in rural areas of regions where trypanosomiasis is prevalent are at risk and should be appropriately cautious.

Clothing can be protective. The clothing should be fairly thick, as the tsetse fly can bite through light fabric. Also, because the fly is attracted to bright colors, clothing should be bland; khaki- or olive-colored clothing is recommended. The clothing should fit tightly at the wrists and ankles to make it harder for flies to enter. Riding in the back of open-air vehicles is unwise; tsetse flies are also attracted to dust. Another wise precaution, which has also proven useful in reducing the incidence of malaria, is the use of protective netting over a bed.

Impacts and Issues

The resurgence of trypanosomiasis during the 1970s highlights the vigilance that is necessary to control infectious diseases and prevent their re-emergence. The loss of control over trypanosomiasis was due to the interruptions in the monitoring of disease outbreaks, the displacement of people due to regional conflicts, and environmental changes. These problems are ongoing. In particular, the documented warming of the atmosphere will make Africa even more hospitable to the spread of the territory of the tsetse fly, which could increase the geographical distribution of trypanosomiasis.

Trypanosomiasis is a major health concern in approximately 20 countries in Africa. The WHO estimates that over 66 million people are at risk of developing the disease. However, fewer than 4 million people are being monitored and only about 40,000 people are treated every year. The proportion of people being monitored or treated is smaller than other tropical diseases, even though trypanosomiasis can increase to epidemic proportions and the death rate for those who are not treated is 100%.

Epidemics disrupt families as well as national economies, as large numbers of people become unable to work or care for themselves. According to WHO estimates, in 2004 the number of healthy years of life lost due to premature death and disability caused by trypanosomiasis was 1.5 million. Since many regions are still agricultural, the rural-based disease affects those who are most important to the economy. Of the 48,000 deaths that occurred in 2004, 31,000 were males, who are often the working family members. Epidemics can decimate the population of a region.

Taking care of those diagnosed with trypanosomiasis is a daunting task for the poor nations, since two-thirds of people diagnosed with the disease already have the advanced stage of the infection, in which the nervous system has been affected. The only treatment that is effective once the central nervous system has been affected—the drug melarsoprol—contains arsenic, and so the treatment itself can sometimes be fatal. Compounding the problem, some strains of the trypanosomes that are resistant to drugs used to treat the disease at an earlier stage have been detected. It seems a matter of time before these resistant strains become more common, as the resistance gives them a selective advantage over nonresistant trypanosomes.

Treatment can also be hampered by the cost of the drugs. An example is eflornithine. Originally developed as an anticancer compound, the drug has been promising against T. brucei gambiense. However, it costs between 300 and 500 U.S. dollars per patient, which makes it unaffordable for mass use by a poor nation.

The WHO is actively involved in programs intended to monitor and treat trypanosomiasis. As one example, since 1975, WHO, the United Nations Children's Fund (UNICEF), the World Bank, and the United Nations Development Program (UNDP) have collaborated on The Special Program for Research and Training in Tropical Diseases. The aim of the program is to develop means of combating infectious diseases, including trypanosomiasis, in a way that is effective and affordable to poorer countries that otherwise are unable to meet the economic and logistical burdens of treatment.

In addition, the WHO Communicable Disease Surveillance and Response unit works with countries experiencing epidemics to set up national programs to control the disease. This can be challenging, since governments can treat trypanosomiasis as a low priority issue until an epidemic strikes. By acting earlier and with a more coordinated national effort, however, epidemics might well be avoided.

Primary Source Connection

With international cooperation among African countries and international health authorities, intensive insecticide spraying, and efficient drug delivery to treat the disease in its early stages, trypanosomiasis was nearly eradicated from Africa in the mid-1960s. By the late 1980s, major epidemics in east and central Africa heralded a dramatic re-emergence of the disease. In the article for the magazine Foreign Policy, author Peter Hotez discusses reemerging diseases, including those that could re-emerge deliberately through acts of bioterrorism, along with the political, social, and natural causes that allow diseases to re-emerge. Peter Hotez is professor and chair of microbiology and tropical medicine at The George Washington University and a senior fellow at the Sabin Vaccine Institute.

Dark Winters Ahead

During the 1990s, the eruption of military conflicts posed one of the strongest stimuli for the reemergence of infectious diseases in poor nations. The civil wars in Angola, Rwanda, and Sudan produced devastating out-breaks of African sleeping sickness, cholera, and polio, even though experts had assumed that these infections had been eliminated a decade or so earlier.

New links between political turmoil and public health crises are forcing the traditional foreign-policy community to consider the latest trends in global disease. Enter Emerging Infectious Diseases, a seven-year-old bimonthly journal published by the Centers for Disease Control and Prevention (CDC) in Atlanta. The journal provides a valuable service by studying infectious agents like the West Nile or Ebola viruses, which have the potential to emerge because of new human or animal migrations or environmental changes. A recent article by Scott Dowell, the acting associate director for global health at the CDC's National Center for Infectious Diseases, examines the seasonal aspects of infectious disease, offering insights that could prove useful to global public health initiatives as well as antibioterrorism efforts around the world.

In an article titled “Seasonal Variation in Host Susceptibility and Cycles of Certain Infectious Diseases,” Dowell explains how human viral epidemics seem to depend on the calendar, suddenly appearing and disappearing with the seasons. A good example is the regular January arrival of influenza in the United States. Similarly, rotavirus gastroenteritis appears in the southwestern United States and then slowly migrates to northeastern cities like Boston and Washington, D.C., striking young children during the winter months. Some 200 years ago, these same cities faced predictable and devastating summer epidemics of yellow fever introduced by cargo ships carrying infected mosquitoes from the West Indies.

Dowell argues that this seasonal variation of infection might not depend solely on the weather, as is commonly thought. He notes that the same viral infection— such as influenza—can appear on both sides of the equator during January, despite it being winter in the North and summer in the South. Because some aspects of human physiology (including sensitivity to light and certain immunities) also vary with the calendar, Dowell maintains, the regular arrival of certain epidemic infections might be explained by seasonal changes in human susceptibility to microbial invasion.

On this particular point, Dowell's hypothesis is less convincing since it diminishes the crucial role of the infectious agent itself in producing a clinical infection. Indeed, infectious pathogens have coevolved with humans in an intricate and remarkable dance that has taken millions of years. Recognizing the tentative nature of his hypothesis, Dowell calls for fellow researchers to review past clinical trials for further evidence.

Nevertheless, Dowell's larger emphasis on the seasonal nature of infection has important implications for the implementation of public health efforts. For instance, when national immunization days are held in polio- and measles-endemic regions of the developing world, they are best conducted well before the seasonal onset of these infections, thus allowing sufficient time for a child's immune system to respond to the vaccine. The same time-urgency applies to so-called days of tranquility, when vaccinations help to implement effective cease-fires in war-torn areas of Central Asia and sub-Saharan Africa.

Dowell's insights can also help those who seek to mitigate the potential impact of bioterrorism attacks. U.S. civil defense officials are concerned by the similarity between the early symptoms produced by biological warfare agents—such as bacterial agents of tularemia and Q fever—with the symptoms produced by influenza. In the initial stages of infection, all three will produce fever, chills, headaches, muscle pains, and appetite loss. The similarity may delay the detection of biological attacks during the winter, when public health officials might erroneously attribute an increase in complaints of such symptoms to a common flu outbreak.

Responding to such concerns, the CDC has initiated a national system of Centers for Public Health Preparedness to ensure that local health workers can respond to a bioterrorism attack. Similarly, the U.S. Defense Department's Advanced Research Projects Agency is developing new technologies aimed at differentiating infectious agents used as biological weapons from common seasonal viruses. However, such efforts are far from sufficient. A January 2001 CDC report concluded that the nation's public health infrastructure is not prepared to detect a bioterrorist event. In June 2001, the Center for Strategic and International Studies and the Johns Hopkins University Center for Civilian Biodefense Studies simulated a bioterrorist attack in a war game exercise known as “Dark Winter.” Their conclusion: A smallpox attack on the United States would produce massive civilian casualties and rapid breakdown of the country's essential institutions. Unfortunately, the United States remains years away from replenishing key vaccine stockpiles and even further from having improved detection technologies in place.

Peter Hotez

HOTEZ, PETER. “DARK WINTERS AHEAD.” FOREIGN POLICY (NOVEMBER-DECEMBER 2001): 84.