Yellow Fever

Yellow fever (YF) is an acute, hemorrhagic, febrile disease caused by a RNA virus of the family Flaviviridae, the yellow fever virus (YFV).¹ This family of viruses embraces several important pathogens that are responsible for human and animal diseases, including Saint Louis encephalitis and Dengue.² The YFV is an arthropod-born virus (arbovirus) vectored by hematophagous mosquitoes. The YFV has originated in Africa and further disseminated to the New World during early colonization periods.¹

Two distinct cycles of transmission of YFV are recognized: a sylvatic cycle and an urban one. In the sylvatic cycle, the YFV is transmitted among non-human primates and a number of blood-sucking mosquito species (Aedes sp in Africa; Haemagogus sp, Sabethes sp, Aedes sp in the Americas). Humans can be infected when invade the wild environment. The urban cycle can be maintained by the transmission among humans and the peridomestic mosquitoes of the species Aedes aegypti.⁴ The urban cycle is associated to improper waste disposal and unplanned urbanization into previously wild areas. Peridomestic mosquitoes may feed on infected non-human primates and subsequently transmit the virus to human beings. Reports have shown that human cases frequently follow outbreaks in non-human primates in the vicinity.^1,3

Due to epidemiologic and ecologic aspects, eradication of the sylvatic cycle of is unfeasible. Urban cycle remains a major human health concern in certain areas of Africa and tropical America.⁴ In Brazil, the urban cycle of the yellow fever virus was considered eradicated in 1942. However, the recurrence of dengue virus and its vector, the Aedes aegypti, associated with the crescent human invasion into wild environments, raises the possibility of YF resurgence in Brazilian metropolitan regions. Non vaccinated humans are at risk of infection and disease if bitten by vectors harboring the virus in endemic regions. Prevention is based on vector control and immunization of humans at risk of exposure using a live attenuated yellow fever virus 17-D strain vaccine.⁴

Infection with YFV has been reported in a wide range of non-human primate species. Among African non-human primate species, YF has been described in baboons (Papio sp.), mangabeys (Cercocebus sp.), chimpanzees (Pan sp.), colobus monkeys (Pilocolobus sp.), African green monkeys (Cercopithecus spp.), and patas monkey (Erythrocebus patas)¹. The YF in African species usually is associated with a few and mild clinical manifestations, and most of the infected individuals overcome the illness without sequelae. On the other hand, in South and Central America, YF can present devastating effects on neotropic primates. Among this group of primates, howler monkeys (Alouatta spp.), spider monkeys (Ateles spp.), and squirrel monkeys (Saimiri sciureus) are particularly susceptible to disease.^1,3 In susceptible neotropic primates, YF is characterized by an acute onset of fever, nausea and vomiting, followed by renal and hepatic failures. Due to disseminated intravascular coagulation, jaundice and hemorrhages from body orifices may occur. Fatality among individuals showing renal and hepatic failures is elevated. Gross lesions are unspecific and include jaundice, hemorrhages in multiple organs, and moderate to severe hepatic lipidic degeneration. Microscopically, the remarkable features are hepatic esteatosis, midzonal hepatic necrosis, and the presence of Councilman bodies, indicating active apoptosis. Treatment of affected non-human primates is palliative and based on supportive care.^1,3

Leishmaniasis

Leishmaniases (LM) are a complex of world-wide diseases with a wide range of clinical and epidemiological features. The disease is caused by protozoan parasites of the genus Leishmania, family Trypanosomatidae, which can infect numerous mammal species, including humans.^1,2 Recent data show that human LM is endemic in 88 countries; 66 of them in the Old World and 22 in the New World.³ It is estimated that 12 million people are infected worldwide. Both human and animal LM have increased their geographic distribution, certainly due to environmental changes and human demographic and behavioral factors.³

Although the taxonomic classification of Leishmania spp. is controversial, up to 30 different species of Leishmania species can be recognized, and as many as 20 of them have shown zoonotic properties.¹

The parasites are vectored into the mammal host by hematophagous sandflies (Phlebotomus sp. in Old World and Lutzomya sp. in the New World). Domestic dogs play a very important role as reservoirs of leishmaniae in urban and rural areas. Other wild canids from New and Old World have also been reported as hosts for leishmaniae, as the foxes, jackals, and wolves in the Old World. The wild crab-eating fox, Cerdocyon thous, and the opossum, Didelphis marsupialis, in South America are firmly placed in the category of natural reservoirs of L. chagasi.⁴ Similarly, the parasites have been reported in a number of other wild vertebrate species, as primates, felids, edentate, and rodents among others. However, the actual epidemiological role played by many of these host species is still uncertain, and they are referred as potential reservoirs.

In humans, LM presents three different clinical manifestations: the visceral leishmaniasis (VL), the cutaneous leishmaniasis (CL), and the mucocutaneous leishmaniasis (MCL), depending on the species of Leishmania involved. The causative agents of VL are L. donovani, L. infantum and L. tropica in the Old World, and L. chagasi in the New World. The CL presents a wider diversity of causative agents in comparison to the other presentations of the disease. In the Old World, L. aethiopica, L. major, L. infantum, and L. tropica are referred as causative agents of CL; in the New World, 11 different epitheliotropic species of Leishmania have been reported.^1,2 In Brazil, 7 species have been described; the most important are L. (V.) braziliensis, L.(V.) guyanensis e L.(L.) amazonensis (Ministério da Saúde, 2007). Clinical manifestations of LM are common in domestic dogs and in determined species of wild canids; limited information is available for other animals host species.¹

The leishmaniae are obligate intracellular pathogens of vertebrate phagocytes. They are in the form of promastigotes when transmitted from their insect vectors, and transform into their amastigote form in the macrophages of the vertebrate hosts.^1,2 Pathological alterations are variable and largely dependent on the clinical presentation of LM (VL, CL, and MCL). The observed lesions are secondary to the effects of the pathogen on the host mononuclear phagocytic system.²

The diagnosis of LM relies in the clinical presentation, in the gross and microscopic appearance of the lesions, and in other laboratorial tools for direct or indirect detection of the parasites. Serologic methods are useful to detect antibodies against leishmaniae (IF, ELISA and Western blotting). For the morphologic identification of the parasites under optical microscopy, culture methods might be required. Diagnostic approaches based in nucleic acids detection methods, as PCR have been increasingly used.^1,2

Treatment of LM in dogs is based on long term administration of pentavalent antimonials drugs (meglumine antimoniate and sodium stibogluconate) and/or allopurinol.^1,5 Data on feline LM therapy is scarce. Successful treatment of a cat with CL was obtained with the association of meglumine antimoniate and ketoconazole.¹ The culling of infected dogs as a control measure against LM has been seen with criticism6. For other wild species, culling poses strong ethical restrictions in addition to be unfeasible under natural conditions. Vaccination of domestic dogs against LM is being viewed as a promising perspective.^1,6

References

Yellow Fever

1.  Mansfield K, King N. Viral diseases. In: Bennett BT, Abee CR, Henrickson R. Nonhuman Primates in Biomedical Research: Diseases. Academic Press, San Diego. P.p. 1-58. 1998.

2.  Fauquet CC, et al. Viral Taxonomy; Eight Report of the International Committee on Taxonomy of Virus. Elsevier, Amsterdam. 1259p. 2005.

3.  Brady AG, Morton DG. Digestive system. In Bennett BT, Abee CR, Henrickson R. Nonhuman Primates in Biomedical Research: Diseases. Academic Press, San Diego. P.p. 377-414.

4.  Strano AJ. Yellow fever. In: Connor DH, Chandler FW, Schwartz, DA, Manz HJ, Lack EE. (Eds) Pathology of Infectious Diseases. Appleton & Lange, Stamford. P.p.383-387. 1997.
 

Leishmaniasis

1.  Baneth G. Leishmaniasis. In: Infectious Diseases of the Dog and Cat. GREENE, G.E. (Ed.). Saunders Elsevier. Saint Louis. P. 685-695. 2006.

2.  DeNigris EC, et al. Leishmaniasis. In: Connor DH, Chandler FW, Schwartz DA, Manz HJ, Lack E.E. (Eds) Pathology of Infectious Diseases. Appleton & Lange, Stamford. P.p.1191-1203. 1997.

3.  Gramiccia M, Gradoni L. Intern. J. Parasitol. 35: 1169-1180, 2005.

4.  Lainson R, Rangel E. Mem. Inst. Oswaldo Cruz 100(8): 811-827, 2005.

5.  Banneth G, Shaw SE. Vet. Parasitol. 106: 315-324. 2002.

6.  Courtnay O, et al. J. Infect. Dis. 186: 1314-1320, 2002.