Disease Characteristics and Transmission
Chagas disease, LF, onchocerciasis, and leprosy are all parasitic infections, but their causative agents, modes of transmission, and geographic distribution differ. Chagas disease is caused by infection with a protozoan, leprosy by a mycobacterium, and LF and onchocerciasis by filarial nematodes. Three are vector-borne diseases, but leprosy is transmitted directly from person to person. Chagas disease occurs only in the Americas, onchocerciasis is found predominantly in Africa, and LF and leprosy occur in all tropical regions.
Chagas Disease
Chagas disease—also known as American trypanosomiasis—is a zoonotic disease caused by the protozoan hemoflagellate Trypanosoma cruzi that is mainly transmitted by large, bloodsucking, reduviid bugs of the subfamily Triatominae (known as kissing bugs). Infection with this blood parasite has been recorded in more than 150 species of 24 families of domestic and wild mammals as well as in humans. In the vertebrate host, T. cruzi usually infects macrophage, muscle, and nerve cells.
Human infection with T. cruzi most commonly originates through contact of broken skin or mucosa with the excretion of infected insect vectors. The incubation period ranges from 7 to 15 days, leading to the acute phase of infection—characterized by patent parasitemia—which may last up to four weeks. The acute phase may be without obvious symptoms. Romana's sign—that is, uniocular, bipalpebral edema with regional lymphadenopathy—is diagnostic of the acute infection but occurs in less than 5 percent of infections.
If a recent infection is untreated, the individual will remain infected for life. After an asymptomatic period of 10 years or more, some 10 to 40 percent of those infected will develop cardiac or digestive complications that are characteristic of the chronic stage of the disease. In chagasic myocardiopathy the most common symptoms are dyspnea and arrhythmias. Electrocardiographic alterations can occur, such as right bundle branch block, left anterior hemiblock, or both, which may require a pacemaker implant. Apical aneurisms are also typical of advanced chagasic cardiopathy, which may rupture on excessive exercise, leading to sudden death. Chagas disease can also involve intestinal complications characterized by severe dilatations of parts of the digestive tract known as megasyndromes. Megaesophagus and megacolon are the most common. Symptoms of megaesophagus are dysphagia and odinophagia and subsequent malnutrition. Chagasic megacolon is characterized by constipation and meteorism. As a result of colon distension and contractions, abdominal pain is frequent, and fecalomas are a complication.
More than 120 species of Triatominae and three transmission cycles are recognized. The domestic cycle, responsible for maintaining infection in humans, occurs mostly in rural or periurban areas where houses have adobe walls and thatched roofs. Humans, dogs, cats, and in some countries guinea pigs are the main parasite reservoirs in this cycle. The vector lives and multiplies in cracks in the walls, holes in the roof, under and behind furniture and pictures, and so on. The sylvatic cycle involves sylvatic triatomine bugs that become infected and in turn infect rodents, marsupials, and other wild animals. The third is the peridomestic cycle in which mammals participate (domestic rodents, marsupials, livestock, cats, dogs) by moving freely in and out of human dwellings, and sylvatic bugs are attracted to lights in houses and to food. This peridomestic cycle acts as a link between the domestic and sylvatic cycles. Occasionally, infected sylvatic species of Triatominae fly into houses and contribute to transmission either by feeding and defecating on the people or their domestic animals or (indirectly) by contaminating food and drink in which the parasites can survive. In the Amazon region, cases of acute Chagas disease have been associated with sylvatic Triatominae contaminating sugarcane or fruit juice.
Transmission by blood transfusion is the second-most common way of acquiring T. cruzi infection. The true incidence of infection through blood transfusion is unknown, because most cases are not recognized. In transfusionally acquired T. cruzi infection, the incubation period is 30 or more days, and the most common symptoms are fever, general lymph node enlargement, and splenomegaly (Schmunis and others 2001).
Transplacental transmission of T. cruzi can occur, and estimates indicate that 5 percent of newborns born to chagasic mothers will become infected. Less common routes of transmission are by transplantation with an infected organ or, more rarely, through contaminated food or infection in the laboratory (WHO 2002a).
Lymphatic Filariasis
LF is caused by species of nematode parasites—Wuchereria bancrofti, Brugia malayi, and Brugia timori—and is transmitted by mosquitoes (WHO 2002c). The adult filarial parasites live in the lymphatics of humans. After mating, each female worm produces several thousand offspring, microfilariae, during its lifetime. The microfilariae are found in humans' internal organs and appear in peripheral blood at times that coincide with the vector's biting activity. The biting mosquito ingests the microfilariae along with the blood meal, and they develop into infective-stage larvae in 10 to 12 days. When an infective mosquito bites a human, the infective-stage larvae are transmitted to the human host and develop into the adult stage in about one year. The adult parasites live 5 to 10 years, of which the fecund life span is 4 to 6 years. Several hundreds to thousands of infective mosquito bites are necessary to establish infection.
Of the three parasite species, W. bancrofti accounts for nearly 90 percent of LF infections worldwide. B. malayi is prevalent only in some parts of South and Southeast Asia, and B. timori is found only in Indonesia. Several species of Culex, Anopheles, Aedes, and Mansonia mosquitoes are involved in the transmission of LF. C. quinquefasciatus is the major vector in Africa, Asia, and South America and transmits nocturnally periodic W. bancrofti. Among anophelines, An. gambiae and An. funestus play a significant role in Africa. Several Aedes species, particularly Ae. polynesiensis, are the major vectors in the South Pacific islands, where diurnally subperiodic W. bancrofti is common. B. malayi is primarily transmitted by Mansonia and Anopheles species.
Infected people can harbor microfilaremia without overt clinical manifestations. The disease process is determined primarily by living adult worms, inflammatory responses caused by the death of adult worms, and secondary bacterial infections. The inflammatory response begins with the death of or damage to adult worms, which leads to host reaction and acute filarial lymphangitis. A heavy worm burden and the presence of worms in the scrotal area precipitate the development of hydrocele, chyluria, chylocele, and lymph scrotum. Lymphatic dysfunction caused by dilatation of the lymphatic vessels makes the patient more prone to repeated secondary bacterial infection, which precipitates lymphedema and elephantiasis. Microfilariae play an important role in the pathogenesis of tropical pulmonary eosinophilia (Dreyer and others 2000).
Onchocerciasis
Onchocerciasis is an infection with the filarial parasite Onchocerca volvulus. The main complications are severe eye disease that can lead to blindness and severe skin disease with unsightly lesions and intense itching (WHO 1995a). O. volvulus is transmitted by vector blackflies of the genus Simulium, whose larvae and pupae develop in rapidly flowing, well-oxygenated streams and rivers. As a result, onchocerciasis is often known as river blindness. The most important vectors are members of the S. damnosum complex in Africa and the Middle East and S. neavei in parts of East Africa. Of the many vectors in the Americas, the most important are S. ochraceum, S. metallicum, S. oyapockense, S. guianense, and S. exiguum.
When taking a blood meal, infected Simulium vectors deposit one or more infective (third-stage) O. volvulus larvae, which reach adulthood in the human host after about a year but may live as long as 14 years. The adult worms typically entwine in nodules where they mate, producing microfilariae that migrate into the skin, eyes, and other organs. These microfilariae are unable to develop into adult worms without first being ingested in the blood meal of a blackfly vector. The microfilariae transform in the vector over a period of 6 to 12 days to produce the third-stage larvae that are infective to humans.
The thousands of microfilariae that do not succeed in reaching a blackfly vector die in the human body, provoking inflammatory reactions in tissues. Inflammation in the eyes leads to irreversible ocular lesions, resulting first in impaired vision and finally in total blindness (WHO 1995a). The death of microfilariae in the skin gives rise to intense itching, dermatitis, depigmentation, and atrophy of the skin (Murdoch and others 2002). A less common complication is lymphadenitis, which may lead to hanging groin and elephantiasis of the genitals, and increasing evidence indicates that onchocerciasis is a risk factor for epilepsy and hyposexual dwarfism in certain areas (Boussinesq and others 2002). The greater is the body load of adult worms and microfilariae, the greater is the risk of developing skin and eye disease.
The disease pattern of onchocerciasis—in particular the severity of ocular disease—varies considerably between geographic zones. Onchocercal blindness can be extensive in hyperendemic communities of the West African savannas, whereas in forest villages with a comparable intensity of infection, the skin manifestations tend to be the main complications of the disease (Dadzie and others 1989; Murdoch and others 2002). These differences may reflect the existence of different vector-parasite complexes, with strains of O. volvulus that differ in pathogenicity (Zimmerman and others 1992). The vector-parasite complex in the West African savanna is responsible for the most severe form of ocular onchocerciasis in the world: in the most affected villages, more than 10 percent of the population may be blind because of onchocerciasis.
Leprosy
Leprosy is caused by Mycobacterium leprae, a gram-positive, strongly acid-fast bacterium. M. leprae is an obligate, intracellular parasite that resides predominantly in macrophages. It is the only bacterium that infects peripheral nerves, showing a preference for Schwann cells, particularly of unmyelinated fibers.
The disease spectrum of leprosy ranges from a single self-healing, hypopigmented macule to a generalized illness causing widespread peripheral nerve damage and affecting even bones and internal organs. Skin lesions may be well- or ill-defined hypopigmented macules, plaques, or nodules that are localized or distributed over the whole skin. They may be hypaesthetic, anesthetic, hyperaesthetic, or have normal sensibility. Nerve lesions occur in dermal nerves as well as in superficial sensory nerves and mixed nerve trunks. One or more nerves may be enlarged on palpation. Signs such as clawing of fingers and toes, "absorption" of digits caused by repeated injury, and dry skin are secondary to impairment of motor, sensory, and autonomic nerve function.
A diagnosis of leprosy is based on finding at least one of three so-called cardinal signs (ILA 2002):
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diminished sensibility in a typical macule or plaque in the skin
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palpable enlargement of one or more peripheral nerve trunks at specific sites
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demonstration of acid-fast mycobacteria in a slit skin smear.
Currently, patients are classified based on clinical signs only, but skin smear results are taken into account when available. Patients who have more than five skin lesions or who have a positive skin smear are classified as multibacillary; others are classified as paucibacillary.
The skin signs of leprosy are relatively harmless, but complications of the disease may lead to severe consequences, such as blindness, infertility, disfigurement, and severe sensory and motor disability. Reactions—that is, episodes of acute inflammation caused by hypersensitivity to bacterial antigens—can be particularly severe. Patients can develop nerve damage without any obvious sign of these reactions, but after neuropathy has become irreversible, it may lead to secondary impairments, such as wounds, contractures, and shortening of digits. As a result of visible impairments or activity limitations—or simply because of the diagnosis of leprosy—many people experience psychosocial problems (van Brakel 2000).
The exact mode of transmission of M. leprae is still not fully understood, but the respiratory tract seems to play an important role. The primary reservoir of infection is the human host. Untreated multibacillary leprosy patients are able to shed large amounts of M. leprae from the nose, and household and social contacts of such patients are at a higher risk of developing leprosy than the general population (van Beers, Hatta, and Klatser 1999). M. leprae-specific DNA sequences have been isolated from the noses of apparently healthy individuals, and widespread seropositivity against M. leprae-specific antigens has been demonstrated in endemic areas, although the role of these individuals in transmitting leprosy is not fully understood. Effective antileprosy treatment usually renders a patient noninfectious within a few days.
