This document summarizes a lecture on tropical diseases given by Dr. Alexandre Naime Barbosa. It discusses several arboviruses including yellow fever, dengue, chikungunya, Zika, and their transmission cycles, geographical distribution, symptoms, pathogenesis, diagnosis, treatment and prevention. The objectives of Dr. Barbosa's educational project are to provide training to health students and professionals, disseminate scientific knowledge to the public, and encourage scientific discussion.

1. Alexandre Naime Barbosa MD, PhD
Infectious Diseases Professor
Winter School on Tropical Diseases
Botucatu School of Medicine - UNESP
2016 - Botucatu - SP - Brazil

2. O material que se segue faz parte do projeto didático do
Prof. Dr. Alexandre Naime Barbosa
Objetivos
1. Ensino: Treinamento de Estudantes e Profissionais da Área de Saúde;
2. Extensão: Facilitar o Contato da População em Geral com Conceitos Científicos;
3. Científico: Fomentar a Discussão Científica e Compartilhar Material Didático.
Autoria e Cessão
1. Conteúdo: Os dados contidos estão referenciados, em respeito ao autor original;
2. Uso: Está permitido o uso do material, desde que citada a fonte;
3. Contato: fale com o autor e conheça o seu projeto didático em:

3. The following material is part of the educational project produced by
Prof. Dr. Alexandre Naime Barbosa
Objectives
1. Education: Training for Students & Health Professionals
2. Community: Provide and Translate Scientific Information to the Population;
3. Scientific: Encourage the Scientific Discussion and Share Teaching Materials.
Authorship and Assignment
1. Content: The following data are referenced in respect to the original author;
2. Use: It is allowed to use the material, if the source is mentioned;
3. Contact: Talk to Dr. Barbosa and keep in touch with his project in:

4. 1. Arbovirus: Overview
2. Yellow Fever
3. Dengue
4. Chikungunya
5. Zika
6. Conclusions

6. So what is the world's deadliest animal?

7. Maybe a smaller animal…

8. Arbovirus: Arthropod Borne viruses
WHO definition: viruses that are
maintained in nature principally, or to an
important extent, through biological
transmission between susceptible
vertebrate host by hematophagous
arthropods; viruses multiply in tissues of
arthropods, and are passed on to new
vertebrates by bites of arthropods after a
period of extrinsic incubation period.

9. Cycle Type 1: Man-Arthropod-Man

10. Cycle Type 2: Animal-Arthropod-Man

11. Family Members
Bunyaviridae La Crosse, Oropouche, Rift Valley, Sandfly, Crimean-Congo
Flaviviridae
Yellow Fever, Dengue, Zika, Japanese Encephalitis,
Saint Louis Encephalitis, West Nile, Kyasanur Forest, Omsk
Togaviridae
Chikungunya, O’nyong-nyong, Ross River, Equine Encephalitis
(East, West, Venezuelan), Sindbis

12. Encephalitis Syndrome
Virus Genus Vector Distribution
EEE Alphavirus Mosq. USA, Canada
WEE Alphavirus Mosq. USA, W. Indies
J.E Flavivirus Mosq. Orient
St. L.E Flavivirus Mosq. USA, C. America
La Crosse Bunyavirus Mosq. USA

13. Fever, with or without rash and arthralgia
Virus Genus Vector Distribution
Chickungunya Alphavirus Mosq. Africa, Asia, C&S Amer.
O’nyong-nyong Alphavirus Mosq. Africa
Sindbis Alphavirus Mosq. Africa, Asia, India
Dengue Flavivirus Mosq. Entire tropics, India
West Nile Flavivirus Mosq. Africa, India
Sandfly Phlebovirus Sandfly Med, Asia, India
Oropouche Bunyavirus Mosq. W.I, South America (N)

14. Hemorrhagic Fever
Virus Genus Vector Distribution
Chickungunya Alphavirus Mosq. Africa, Asia, C&S Amer.
Dengue Flavivirus Mosq. Entre tropics
Yellow Fever Flavivirus Mosq. Africa, S. America
Kyasanur Forest Disease Flavivirus Tick India(Karnataka)
Omsk HF Flavivirus Tick Russia
Crimean-Congo HF Nairovirus Tick Africa, Asia, E.U.

15. CDC - 2015

17. Family: Flaviviridae; Genus: Flavivirus
Distribution: restricted to Africa & Central and South America.

18. Family: Flaviviridae; Genus: Flavivirus
Distribution: restricted to Africa & Central and South America.

19. Brazil: Endemic vs Transition vs Free Areas

20. Brazil: Endemic vs Transition vs Free Areas

21. São Paulo State: Endemic vs Transition vs Free Areas

22. Botucatu 2009 Epidemic

23. Brazil: YF in 2012-13

24. Transmission:

25. Symptoms
The majority of persons infected with yellow
fever virus have no illness or only mild
illness.
In persons who develop symptoms, the
incubation period (time from infection until
illness) is typically 3–6 days.
The initial symptoms include sudden onset
of fever, chills, severe headache, back pain,
general body aches, nausea, and vomiting,
fatigue, and weakness. Most persons
improve after the initial presentation.

26. Symptoms
After a brief remission of hours to a day,
roughly 15% of cases progress to develop a
more severe form of the disease. The severe
form is characterized by high fever, jaundice,
bleeding, and eventually shock and failure of
multiple organs. Rate of Death: 50%

27. Pathogenesis

28. Diagnosis
Virus isolation
– From the blood or post-mortem liver tissue
Rapid diagnostic test:
– Detection viral genome by PCR in blood o tissues
– Not widely available
Detection IgM antibodies (ELISA)
– Simple sample provides a presumptive
diagnosis. Confirmation is made by a rise
between paired acute and convalescent samples
or a fall between early and late convalescent
samples.
– Cross-reactions with other flaviviruses
complicate the diagnosis particularity in Africa
(multiple flaviviruses cocirculate).

29. Treatment
No specific treatments have been
found to benefit patients with yellow
fever. Whenever possible, yellow
fever patients should be hospitalized
for supportive care and close
observation.
Treatment is symptomatic. Rest,
fluids, and use of pain relievers and
medication to reduce fever may
relieve symptoms of aching and
fever.

30. Prevention
Vaccine:
- Types: Inactivated mouse brain or Live attenuated
- Mandatory for people that live at endemic area and
travelers
Others
- Use insect repellent
- Wear proper clothing to reduce mosquito bites
- Be aware of peak mosquito hours

32. Family: Flaviviridae; Genus: Flavivirus, 4 Serotypes (1,2,3,4)
Distribution: all tropical and some subtropical areas
- WHO: 2.5 billion people, two fifths
of the world's population, at risk from
dengue and estimates that there may
be 50 million cases of dengue
infection worldwide every year. The
disease is endemic in more than 100
countries

33. Brazil: 2014 - 2015 Epidemic

34. Brazil: 2014 - 2015 Epidemic

35. Transmission: 1 patterns (Cycle)
1. Person to person transmission by Aedes
A. aegypti (America) and A. albopictus (Asia)

36. Classic Dengue (Break bone Fever)
- Incubation: 3-10 days;
- Chills, high fever, intense headache, myalgia,
arthralgia, retro-orbital pain, colic pain and
abdominal tenderness. Fever biphasic (saddle
type).
- Maculopapular rashes develop on chest, trunk.

37. Dengue Hemorrhagic Fever (DHF) &
Dengue Shock Syndrome (DSS)
C/F-High fever, hemorrhagic phenomena
including bleeding from the eyes, nose, mouth,
ear, into the gut, and oozing of blood from skin
pores, thrombocytopenia, and
hemoconcentration
Vascular leak syndrome - blood leaks through
the skin and into spaces around the lungs and
abdomen. This fluid loss and severe bleeding can
cause blood pressure to fall; then Dengue Shock
Syndrome (DSS) sets in, which has a high
mortality rate.

38. Pathogenesis

39. Diagnosis
- Isolation of virus from blood
- Serology:
-Antibody detection IgM
-Antigen detection- NS1 ag
- RT-PCR

40. Treatment
No antiviral therapy available
Symptomatic management in majority of cases
Suitable fluid replacement

41. Prevention

43. Family: Togaviridae; Genus Alphavirus
Distribution:

44. Brazil: 2014 Epidemic

45. Brazil: 2014 Epidemic

46. Transmission: 2 patterns (Cycles)
1. Person to person transmission by Aedes sp.
2. Monkey-monkey by arboreal mosq. A. aegypti (America) and
A. albopictus (Asia)

47. Symptoms
- Fever
- Severe arthritis
- Chills, headache, photophobia
- Nausea, abdominal pain
- Rashes and petechias

48. Clinical Findings

49. Diagnosis
- Isolation of virus from blood
- Serology: Antibody detection IgM/IgG
- RT-PCR

50. Treatment and Prevention
No antiviral therapy available
Symptomatic management in majority of cases
No available vaccine

52. Family: Flaviviridae; Genus: Flavivirus
Distribution:

53. 14

54. - 1940 - 50: First evidences of human infections (Zika = Forest in Uganda)

55. - 1940 - 50: First evidencies of human infection (East Africa)
- 2007: Big epidemic in Yap Island and Micronesia (80% of total population)
- 2013: French Polynesia (neurologic complications, and others)
- 2015: Brazil and South America (Microcephaly)

56. Beginning of 2015:
- 21 cases of “Dengue-Like”: 8 RT-PCR ZKV Positives (Natal - RN)

57. First Identifield Cases:
- April 2015: Camaçari (BA)
- May 2015: Natal (RN)
- May 2015: Sumaré (SP)
Route Theory
- Va’a (Canoe) World Sprint Championships (RJ, Ago/2014)
- Ocean Pacific Countries: French Polynesia, New Caledonia, Cook Island, Easter Island
- Zika circulation starts in 2014
- Brazil Zika virus is close to Polynesia virus

60. Brasil, Ministério da Saúde - 2016
Dados Oficiais do Surto 2015-16 (23/02/2016)
Confirmados 583
Óbitos 120
Zika Identificado 67
Casos Suspeitos 4.107
Descartados 950

61. - Família: Flaviviridae
- Gênero: Flavivirus
- Vírus RNA
- Arbovírus
- Duas linhagens
- Africana
- Asiática
CDC - 2016

62. Importância Epidemiológica: Transmissão Vetorial
- Aedes aegypti, Aedes africanus e outros Aedes
- Culex???

63. Transmission: 2 patterns (Cycles)
1. Person to person transmission by Aedes sp.
2. Monkey-monkey by arboreal mosq.
Aedes aegypti
Aedes africanus,
Aedes apicoargenteus
Aedes furcifer
Aedes luteocephalus
Aedes vitattus

64. Outras Vias de Menor Importância Epidemiológica
- Transplacentária e Perinatal
- Transfusional
- Sexual
- Saliva e Urina (???)
- Leite Materno (??????)

65. - Período de Incubação (Mosquitos): 10 dias
- Reservatórios de Importância: Humanos e Pequenos Primatas
- Infecção em Humanos:
Células Dendríticas
Linfonodos
Corrente Sanguínea
- Sintomas Clínicos: Leves a Moderados (Febre, Rash Cutâneo e Conjuntivite)
- Associação Possível e Provável com Malformações Fetais e Sde. de Guillain-Barré
- Associação Causal e Dano Neurológico Direto (e outros): em estudo e análise

66. - Microcefalia pode ocorrer, mas não se limita a esse achado (Z-TORCH)
- Podem ocorrer medidas normais de PC, mas com graves malformações de SNC
- Necrose tecidual => Redução massa cerebral => Microcefalia
- Lisencefalia, hidrocefalia, calcificações multifocais corticais e subcorticais
- Perda do tecido cortical, e presença de necrose e inflamação
- Lesões oftalmológicas: mácula e peri-mácula; nervo óptico
- Artrogripose: endurecimento da musculatura e as articulações
- Taxa de Transmissão Transplacentária: 2-5% (???)
- ZKV no feto: permanência e reativação por um longo período
- Momento de maior risco na gestação (???)

67. 18/Nov/2015

68. 10/Fev/2016

69. 13/04/2016

72. Pacientes com quadro de exantema máculo-papular e DOIS dos seguintes sintomas:
- febre (<38,5º C) ou
- hiperemia conjuntival sem secreção ou
- prurido ou
- artralgia ou
- edema periarticular
Outros Achados: mialgia, cefaleia, edema de membros inferiores, dor retrorbital,
anorexia, vômitos, diarreia ou dor abdominal.
Manifestações neurológicas:
- Síndrome de Guillain Barré, ADEM: 4 a 20 dias após o início dos sintomas

73. Symptoms
About 1 in 5 people infected with Zika virus
become ill.
The most common symptoms of Zika are fever,
rash, joint pain, or red eyes. Other symptoms
include muscle pain, headache, pain behind
the eyes, and vomiting.
The illness is usually mild with symptoms
lasting for several days to a week.
Severe disease requiring hospitalization is
uncommon.
Deaths due to Zika are very rare.

74. Matsuda EM - 2016

75. Brasil, Ministério da Saúde - 2016

76. Treatment and Prevention
No antiviral therapy available
Symptomatic management in majority of cases
No available vaccine

78. Não há vacina
Eliminação dos criadouros dos mosquitos
Evitar locais com presença do mosquito, uso de telas
Repelentes
- < 6 meses: sem indicação
- 6 meses - 2 anos: IR3535
- 2 anos a 12 anos: DEET 10% (no máximo, aplicar 3x/dia) ou Icaridina;
> 12 anos ou gestantes: DEET > 10% ou Icaridina
Uso de inseticidas
Uso de cobertura de áreas expostas com roupa
Atualização de carteira vacinal

81. Comparison of Symptoms (Chikungunya, Dengue anda Zika)

85. Obrigado pela Atenção!
SAE de Infectologia HC UNESP Botucatu Faculdade de Medicina UNESP