Disease Characteristics and Transmission
Dengue
Dengue is a mosquitoborne viral disease with a high capacity for epidemic outbreaks. Infection can be asymptomatic or can present with symptoms ranging from mild, self-limiting, febrile illness to severe, life-threatening disease. Two clinical pictures are recognized: (a) dengue fever (DF) and (b) dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS).
The four dengue serotypes, known as dengue 1, 2, 3, and 4, constitute a complex of the flaviviridae transmitted by Aedes mosquitoes, particularly Ae. aegypti. Infection by any of the four serotypes induces lifelong immunity against reinfection by the same serotype, but only partial and transient protection against the others. Sequential infection by different serotypes seems to be the main trigger for DHF/DSS.
Disease Manifestations
The incubation period is four to six days. Infants and young children usually develop fever, sometimes accompanied by a rash. Older children and adults may develop either a mild febrile syndrome or classic DF with fever, headache, myalgias, arthralgia, nausea, vomiting, and rash. Skin bleeding, petechiae, or ecchymosis are observed in some patients. Bleeding from the nose, gums, and gastrointestinal tract; hematuria; or hypermenorrhea can accompany the clinical picture. Leukopenia is common and thrombocytopenia is sometimes observed. DF can be incapacitating, but the prognosis is favorable and the case-fatality rate is low.
By contrast, DHF/DSS can be life threatening. It is characterized by high fever, bleeding, thrombocytopenia, and hemocon-centration (Nimmanitya 1993; PAHO 1994). Plasma leakage differentiates DHF/DSS from classic DF. Severity is classified as mild (grades I and II) or severe (grades III and IV), with the main difference being shock in the latter. In some epidemics, hepatomegaly has been prominent. As with DF, DHF generally begins with a sudden temperature rise accompanied by facial flush and other nonspecific manifestations, such as anorexia, vomiting, headache, and muscle or joint pains. The most common hemorrhagic manifestation is a positive tourniquet test, although petechiae, ecchymosis, epistaxis, and gingival or gastrointestinal bleeding may also be observed. After three or four days, when the temperature returns to normal or below, the patient's condition can suddenly deteriorate with signs of circulatory disturbance. The patient may sweat, be restless, have cool extremities, and show changes in pulse rate and blood pressure. Many recover spontaneously or after brief fluid therapy, but some proceed to shock with typical signs of circulatory failure. Initially patients may be lethargic but become restless and rapidly enter a critical stage of shock. Some patients evolve to severe circulatory failure (DSS), presenting a rapid and weak pulse, a narrow pulse pressure or hypotension, cold and clammy skin, and an altered mental state. DSS is fatal in 5 to 10 percent of cases if fluid management is inadequate or delayed.
Transmission and Epidemiological Trends
The dengue virus is transmitted from humans to humans by Aedes mosquitoes, of which the most important is Ae. aegypti (Bennett and others 2002; Gubler 1979; Tardieux and others 1990). Female mosquitoes ingest the virus while feeding on viremic individuals, and after an 8- to 12-day incubation period they can transmit the virus to other humans during blood feeding (Watts and others 1987). Thereafter, the female mosquito remains infective for life. Transmission of the virus from infected females to their progeny has been documented, but its epidemiological significance is not well understood (Hull and others 1984; Rosen and others 1983).
Although believed to be of African origin, Ae. aegypti is now established throughout the tropics and subtropics, exploiting almost any water-filled container as larval habitat. Ae. aegypti is also the urban vector of yellow fever. Ae. albopictus also transmits dengue and is an important secondary vector in parts of Southeast Asia and the Pacific. This species is of Asian origin but has spread to parts of Africa, the Americas, and Europe by depositing egg masses in used car tires, which are traded around the world.
Major epidemics of denguelike illness were documented in the 18th and 19th centuries in Africa, the Americas, and Asia, and clinical descriptions of illness compatible with dengue in China date from about 265. During 1900-50, dengue epidemics occurred in Australia, China, Greece, India, Japan, Malaysia, Thailand, and Vietnam and in the Caribbean (Gubler and Kuno 1997). DHF was first recognized in the 1950s, although a similar hemorrhagic fever was reported in Philadelphia in 1780, in Australia in 1897, and in Greece in 1928. Dengue is now endemic in Africa, the Americas, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. According to WHO, it occurs in more than 100 countries and an estimated 2.5 billion people are at risk.
The increase in dengue epidemics can be attributed to rising levels of urbanization, which promote contact between humans and Ae. aegypti; inadequate domestic water supplies; and increasing international travel, migration, and trade, which help disseminate vectors and the virus. Epidemiological changes in the Americas since the 1970s illustrate this process. During the 1940s through the 1960s, the Ae. aegypti control program was successful in most of the region, with several countries declaring complete eradication. However, after some years, reinfestation with Ae. aegypti was apparent, and by 1995 it had returned to most of the previously infested countries. Reinvasion by the vector was followed by increased circulation of the virus, and the region evolved from nonendemic to hypoendemic (sporadic epidemics caused by a single serotype) to hyperendemic (simultaneous circulation of multiple serotypes resulting in frequent epidemics). DHF became a major public health problem. Before 1981, 5 countries in the region reported only a few cases of DHF, but by 2002, 21 countries reported more than 14,000 cases and 250 deaths (Gubler 2002; Guzman and Kouri 2002; Guzman and Kouri 2003; Guzman and others 2002).
Leishmaniasis
Leishmaniasis (or the leishmaniases) refers to infections caused by protozoan parasites of the genus Leishmania transmitted by female sandflies (Phlebotominae). More than 20 Leishmania species are pathogenic to humans, and more than 30 species of sandflies are proven vectors. The disease tends to be focal in distribution. In anthroponotic foci, sandflies transmit parasites from human to human, and in zoonotic foci, sandflies transmit the parasites between mammal hosts and from them to humans.
Disease Manifestations
The different species of Leishmania cause illness of differing severity. Visceral leishmaniasis (VL), caused by species of the L. donovani complex, is usually fatal if untreated. Mucocutaneous leishmaniasis, caused by the L. braziliensis complex, is highly disfiguring and mutilating, and it can be fatal because of secondary complications. Cutaneous leishmaniasis (CL), caused by the L. major, L. donovani, and L. braziliensis complexes, may be a simple, self-limiting skin ulcer, but it can be disabling when numerous lesions occur. Diffuse cutaneous leishmaniasis, caused by the L. mexicana and L. aethiopica complexes, is longer lasting because of deficient immune responses.
Epidemiological Trends
Leishmaniasis is found in 88 countries worldwide. VL occurs in 62 of those countries, with most of the estimated 500,000 annual cases occurring in poorer rural and suburban areas of Bangladesh, Brazil, India, Nepal, and Sudan. Mucocutaneous leishmaniasis is mainly limited to South and Central America, whereas most of the estimated 1 million to 1.5 million annual CL cases occur in the Middle East (Afghanistan, Algeria, the Islamic Republic of Iran, Saudi Arabia, and the Syrian Arab Republic) and in Brazil and Peru (Desjeux 1996). Reliable data on incidence and prevalence are scarce because only 33 endemic countries provide official notification of infection.
Leishmaniasis transmission is increasing in several areas. For example, the number of cases of CL in Kabul, Afghanistan, increased from 14,200 in 1994 to 65,000 in 2002, and the number of cases of VL in northeastern Brazil increased from 1,840 in 1998 to 6,000 in 2002. Such increases reflect the following environmental, land-use, and behavioral changes that increase exposure to the sandflies:
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Rural-urban migration seems to have contributed to urbanizing VL in Brazil, whereas in East Africa, VL seems to be more closely associated with migrations of seasonal workers and refugees. Transborder migrations between Bangladesh, India, and Nepal are also a risk factor for VL.
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New settlements in high-risk endemic areas, such as those established by people migrating from high plateaus to tropical plains in some Andean countries, increase their exposure to vectors.
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Development in areas of zoonotic transmission, such as road building, mining, oil prospecting, forestry, and eco-tourism, and military activity increase risks for those involved (Desjeux 2001).
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Deteriorating social and economic conditions in the poorer suburbs of some cities may contribute to increasing transmission, especially of VL.
Leishmaniasis can be an opportunistic infection in people with HIV/AIDS, and coinfections have been reported in 34 countries (Desjeux and Alvar 2003). Malnutrition or HIV/AIDS coinfection can also increase disease severity by impairing the immune response.
African Trypanosomiasis
African trypanosomiasis is caused by parasites transmitted by tsetse flies (Glossinidae). The most important are forms of Trypanosoma brucei that infect humans and livestock, and T. congolense and T. vivax that infect only livestock. Human infection causes severe disease known as sleeping sickness, which is acute in the case of infection with T. brucei rhodesiense but more chronic with T.b. gambiense. Both forms lead to central nervous involvement and are fatal without appropriate treatment.
Disease Manifestations
Parasites are transmitted by the bite of infected tsetse flies. They multiply locally in extracellular spaces, producing a characteristic lesion or chancre. The parasites circulate in blood and lymph, resulting in waves of parasitemia with episodes of fever, often accompanied by chills, rigor, malaise, prostration, and weight loss. These symptoms may occur within days of development of the chancre and constitute the hemolymphatic early stage. Febrile episodes become less severe as the disease progresses, and after a variable period the parasites invade the central nervous system and cerebrospinal fluid, leading to the late stage, with meningoencephalitis typically accompanied by severe and protracted headache, apathy, sleep disorders, irritability, and antisocial behavior.
The clinical features of late-stage sleeping sickness can resemble AIDS. With T.b. rhodesiense, meningoencephalitis typically occurs within weeks of initial infection, whereas with T.b. gambiense, this syndrome occurs later, sometimes after several years. Untreated disease causes relentless deterioration in cerebral function, with patients becoming increasingly difficult to rouse and passing into coma and death. Infection does not seem to confer immunity, so reinfection can occur after treatment.
Transmission and Vectors
Male and female tsetse flies are obligate bloodsuckers and can transmit trypanosomes, which undergo cyclical development in the infected flies. With T.b. gambiense, the main reservoir host is people, so tsetse flies mainly transmit from person to person, although increasing evidence suggests that pigs and some other animals are also important reservoirs. With T.b. rhodesiense, the main reservoir hosts are cattle and related animals, so transmission occurs mainly from animals to humans, although transmission from human to human also occurs (Okoth 1986). Mechanical (Frezil 1983), sexual (Rochas and others 2004), and transplacental (De Raadt 1985; Libala, Wery, and Ruppol 1978; Traub and others 1978) transmission have been described but are believed to be insignificant.
Thirty-one species and subspecies of Glossina are recognized. All probably can transmit trypanosomes, but only eight are known vectors for human infection. Animal trypanosomiasis can be found wherever wild tsetse flies occur, but human trypanosomiasis is usually associated with historic foci with strong epidemic potential. Most T.b. gambiense transmission is attributed to G. palpalis species occupying riverine and forest habitats in West and Central Africa, whereas T.b. rhodesiense transmission is mainly attributed to G. morsitans species in East African savannas. G. fusca species, although important vectors of animal trypanosomiasis, are considered insignificant for human forms.
Tsetse flies have an unusual life cycle. An inseminated female nurtures the egg and larva in her uterus, depositing the mature larva on the ground, where it burrows and pupates. Thus, each female produces only one offspring at a time. She produces up to 12 during her two- to three-month adult life span. The intrinsic population growth rate is low. Even small increases in average daily mortality rates can cause population decline, even to extinction.
Epidemiological Trends
Tsetse flies occur in parts of 37 countries in Sub-Saharan Africa. Animal trypanosomiasis is widespread throughout this region, but human disease is focused in areas of 20 countries. Over the entire tsetse-fly belt, WHO estimates that 60 million people are at risk of infection, with a standing prevalence of about 300,000 infections. Of these, probably fewer than 15 percent are diagnosed and treated (Cattand, Jannin, and Lucas 2001). For T.b. rhodesiense, epidemiological work in Uganda estimated that for every individual correctly diagnosed and treated, a further 12 cases are undiagnosed and unreported (Odiit 2003). The incidence of sleeping sickness has been increasing steadily since the 1970s, with epidemics in several areas, particularly the Democratic Republic of Congo (DRC) and northern Angola. In 1998-99, some 45,000 new cases were reported each year, representing a 10-fold increase since the 1960s. Most current epidemics are due to T.b. gambiense, although major epidemics of T.b. rhodesiense occurred in Uganda in 1978, 1980, and 1988.
The apparent increase is largely attributable to a decline in tsetse and trypanosomiasis control operations, which are influenced both by changing political priorities and by civil unrest and war. In the DRC, some 10,000 cases were diagnosed annually during the 1980s, but after four years with little or no control, the number of reported cases rose to 30,000 per year. In Angola, cases rose sixfold following the interruption of control operations because of war. Transmission is also occurring in new locations. In 1999, urban and periurban transmission was reported in Kinshasa, DRC, and in Luanda, Angola, and a new focus was reported in Soroti, Uganda, where an epidemic of T.b. rhodesiense disease followed the introduction of infected cattle (Fevre and others 2001).
