LEPTOSPIROSIS
DENGUE
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
LEARNING OBJECTIVES
Understand the chain of transmission of arthropod-borne
viruses in general
Describe the clinical syndrome associated with arthropod
borne viruses
Characterize the Dengue virus
Discuss the clinical course of Dengue fever
Discuss the clinical features DHF and DSS
Discuss the supportive measures necessary in the care
Dengue patient
2005 (dengue outbreak(
Dengue Virus
Is an arbovirus
Transmitted by mosquitoes
Dengue Viruses
Each serotype provides specific lifetime immunity,
and short-term cross-immunity
Incubation Incubation
Period Period
Viremia Viremia
0 5 8 12 16 20 24 28
Illness Illness
DAYS
HUMAN # 1 HUMAN # 2
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
Replication and Transmission
2008-2009
(of Dengue Virus (Part 1
1. Virus transmitted
to human in
1
mosquito
saliva 2
2. Virus
replicates 4
3. in target
Virus organs
infects
white 3
blood cells and
lymphatic tissues
4. Virus released
and
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine Replication and Transmission
2008-2009
(of Dengue Virus (Part 2
5. Second mosquito
ingests virus with
blood
6. Virus replicates 6
in mosquito midgut
and other organs,
infects salivary 7
glands
7. Virus replicates
5
in salivary
glands
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
Dengue transmitted by
infected female
mosquito
Primarily a daytime
feeder
Dengue
:Alarm Signals
Severe abdominal pain •
:Four Criteria for DHF Prolonged vomiting •
Fever • Abrupt change from fever •
Hemorrhagic manifestations • to hypothermia
Excessive capillary • Change in level of •
permeability consciousness
mm3 platelets/100,000 ≤ • (irritability or somnolence)
Initial Warning
:Signals When Patients Develop
Disappearance of fever • :DSS
Drop in platelets •
Increase in hematocrit • to 6 days after onset of 3 •
symptoms
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009 Severity Grading of DHF
Grade 1 •
Fever and nonspecific constitutional symptoms –
Positive tourniquet test is only hemorrhagic manifestation –
Grade 2 •
Grade 1 manifestations + spontaneous bleeding –
Grade 3 •
Signs of circulatory failure (rapid/weak pulse, narrow pulse –
pressure, hypotension, cold/clammy skin
Grade 4 •
(Profound shock (undetectable pulse and BP –
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009 Clinical Evaluation in Dengue
Blood pressure •
Hydration status •
Tourniquet test •
Tourniquet Test
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
Dengue-specific tests •
Virus isolation –
Serology –
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
Diagnostic Tests
Virus isolation is the gold standard •
LEARNING OBJECTIVES
Describe the incidence & prevalence of Leptospirosis
in the Philippines and worldwide
Describe the chain of transmission of Leptospirosis
Describe the etiologic agent of Leptospirosis
Discuss the pathogenesis of Leptospirosis
Discuss the temporal profiles of the clinical features,
including anicteric and Weil’s disease
Discuss the appropriate use of diagnostic tests: MAT,
MCAT, IHA, ELISA
Discuss the appropriate antimicrobial agents and the
chemoprophylaxis against Leptospirosis
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
INCIDENCE
Leptospirosis is a worldwide zoonotic infection and now identified as
one of the emerging infectious diseases
:Human Infections
Occupational
Direct Contact
• farmers
• veterinarians
• abattoir workers
• meat inspectors
Indirect
• sewers
• miners
• soldiers
Serological Classification & Groupings
• septic tank cleaners
• canal workers Hosts Serogroups
RATS L. Icterohaemorrhagiae
Recreational
MICE L. Ballum
,water sports, swimming DAIRY CATTLES L. Hardjo, Pomona
,canoeing, water rafting DOGS L. Canicola
potholing, caving SHEEP L. Hardjo
Avocational exposures PIGS L. Pomona, Tarassovi
,barefoot walking
flood swimming HUMANS L. Icterohaemorrhagiae
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
Genomospecie
Serogroup Genomospecies Serogroup
s
Andamana
Australis
Manhao L. biflexa
Codice
[[non-pathogenic
Autumnalis
Mini
Semaranga
Ballum
Panama
L. borgpetersenii
Bataviae
Pomona
Canicola L. inadai
Pyrogenes
Celledoni
Ranarum
L. noguchii
Cynopteri
L. interrogans Sarmin
[[pathogenic
Djasiman L. santarosai
Sejroe
Grippotyphosa
Shermani L. weilii
Hebdomadis
Tarassovi
L. kirshneri
Icterohaemorrhagiae
Javanica L. meyeri
Louisiana
L. wolbachii
Lyme
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
PATHOGENESIS
PORT
OF Small Blood Vessel –vasculitis
ENTRY
Kidney –& interstitial nephritis
tubular necrosis
Biphasic stages
Anicteric Leptospirosis
- Acute leptospiremic phase .1
,Non-specific flu-like symptoms as fever and chills -
severe headache usually frontal and retrobulbar w/photophobia
nausea and vomiting
muscle pain affecting the calves, back and abdomen
mental confusion
pulmonary involvement as cough with some hemoptysis
- Signs of conjunctival suffusion is evident
less common are myalgias, lymphadenoathy, hepatosplenomegaly,
rashes in any form
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
CLINICAL FEATURES
ESR- elevated (anicteric leptospirosis) peripheral leukocyte count range from 3,000 to
Ul with left shift; (Weil’s Syndrome) marked leukocytosis/26,000
CSF - slightly elevated protein, normal glucose level but there is increase of polymorphs
followed by mononuclear cell increases
RADIOGRAPHIC FINDINGS - the affected lower lobes shows patchy alveolar pattern
that corresponds to alveolar hemorrhages
DIAGNOSIS
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
Definitive Diagnosis
Isolation of the organism from the patient
Presumptive
MAT with antibody titer of >1:100
ANTIGEN DETECTION
( MICROSCOPIC AGGLUTINATION TEST ( MAT
reference method for serological diagnosis of leptospirosis -
patient sera is mixed with live antigen suspensions of leptospiral serovars -
after incubation, the serum-antigen mixture are examined microscopically for -
agglutination and titers are determined
CDC case definition,a titer of >200 = probable case w/clinically compatible illness
Endemic Countries: a single titer of >800 in symptomatic patients is indicative of Lep
Acute Infection: may go as high as >25,600
DIAGNOSIS
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
Severe Leptospirosis
- Intravenous Penicillin-G, Amoxycillin, Ampicillin or Erythromycin
- Weil’s syndrome may require dialysis for renal failure, may need
transfusion of whole blood/or platelets
Geographical Distribution
Worldwide: 300 – 500 million cases
SOURCE: Div of Parasitic Diseases, Nat’l Center for Infectious Diseases, CDC
THE TOP TEN CAUSES
WHO OF DEATH (2005)
Low-income countries Deaths in millions % of deaths
Coronary heart disease 3.29 11.4
Lower respiratory infections 2.72 9.5
HIV/AIDS 2.06 7.2
Stroke and other cerebrovascular diseases 1.83 6.4
Perinatal conditions 1.72 6.2
Diarrhoeal diseases 1.58 5.2
Tuberculosis 1.01 3.5
Chronic obstructive pulmonary disease 0.97 3.4
Malaria 0.87 3.2
Category D Provinces
• 16 provinces (from 13 provinces)
• 16 provinces remain malaria-free
status
CLIMATE
ANOPHELES MOSQUITOES
HUMAN HOSTS
PARASITES
BIOLOGIC CHARACTERISTICS
Genetic Factors
• Sickle cell traits – heterozygotes for
abnormal
hemoglobin genes Hbs protective from
P. Falciparum
Characteristic of Malarial
Parasites
- P Falciparum causes more disease and death
- P. vivax & ovale have stages that can remain dormant
in
the liver and can cause relapse
- P. falciparum have developed strains that are
resistant to
antimalarial drugs
- Travelers to malaria-risk areas should use
prophylactic
CLINICAL FEATURES OF MALARIA
Because of its”
protean
manifestations,
Malaria can mimic any
kind of disease except
“pregnancy
CLINICAL FEATURES OF MALARIA
Classical Triad of Malaria
Fever .1
Chills .2
Sweating .3
:Other significant features
Headache - Mild jaundice -
Myalgia - Anemia -
G I disturbances - Hepatosplenomegaly -
MANIFESTATION OF SEVERE MALARIA
Unarousable coma/cerebral malaria
Acidemia/acidosis
Severe normochromic, normocytic anemia
Renal failure
ADRS/Pulmonary edema
Hypoglycemia
Hypotension/shock
Bleeding/DIC
Convulsion
Hemoglobinuria
CHRONIC COMPLICATIONS OF MALARIA
HYPERACTIVE MALARIAL SPLENOMEGALY
chronic or repeated malarial infections living -
from endemic areas
exhibit abnormal immunologic response due -
to repeated infections
immunologic process stimulates reticuloendo -
thelial hyperplasia eventually towards spleen
enlargement
HMS presents with an abdominal mass or a -
dragging sensation in the abdomen
persons with HMS who are living in endemic -
areas should receive chemoprophylaxis
blood smear must be air-dried, fixed, stained and the red cells in -
the tail of the film should be read under oil immersion
FINDINGS ON MICROSCOPE
P. P. Vivax P. Ovale P
Falciparum Malariae
MORPHOLOGY Usually only ring Irregularly Infected ery- Band or
forms, banana- shaped large throcytes, rectangular
shaped rings, enlarge enlarged forms of
gametocytes erythrocytesm and oval, trophozoites
Shuffners dots Shuffners common
dot
PIGMENT BLACK YELLOW DARK BROWN
BROWN BROWN BLACK
ANTIMALARIAL AGENTS
68
Pamantasan Ng
Learning Objectives
Lungsod Ng Maynila
College of Medicine
2008-2009
Key Characteristics
Lungsod Ng Maynila
College of Medicine
2008-2009
:Transmission
Person-to-person transmission
Outbreak investigations
Unclear of infection source
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
The "first" pandemic of 1510 travelled from Africa and spread across Europe
The "", 1889–1890. Was first reported in May of 1889 inBukhara , Russia.
By October, it had reachedTomsk and theCaucasus. It rapidly spread west
and hit North America in December 1889, South America in February – April
1890, India in February-March 1890, and Australia in March – April 1890. It
was purportedly caused by the type of flu virus and had a very high attack
. andmortality rate
Pamantasan Ng
:Communicability
Viral shedding can begin 1 day
before symptom onset
:Incubation period
Time from exposure to onset of
symptoms
(to 4 days (average = 2 days 1
:Seasonality
In temperate zones, sharp peaks in
winter
months
Pamantasan Ng
Lungsod Ng Maynila
Abrupt onset
Point-of-care tests
Generally 70+% sensitive, 90+% specific
Can provide results <30 minutes
Immunofluorescence
Requires intact cells and laboratory skill/experience
Serology
Must used paired serum samples>2 week delay for result
RT-PCR
Mostsensitive
Becoming more widely available
Influenza-Like Illness Reported at the Sentinel Sites
of National Influenza Surveillance System, 2006
Female Male
>50 32 18
40-49 36 15
30-39 63 27
Agegroup 20-29 91 43
1000 800 600 400 200 0 200 400 600 800 1000
No. of Cases in Thousands
Table 5. Distribution of Influenza Virus Isolates by Month
Philippines, January 1 to December 31, 2006 (N=4,400)
Virus Isolate Result Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Total
ADENOVIRUS 17 6 12 4 23 5 5 4 8 4 1 9 98
ENTEROVIRUS 7 3 2 2 1 5 2 0 0 2 6 5 35
HSV-1 6 3 2 4 4 2 1 1 0 4 4 1 32
INFLUENZA A 3 0 0 0 21 53 57 53 32 20 16 9 264
INFLUENZA B 0 0 0 0 0 1 11 21 46 31 18 2 130
NEGATIVE 230 100 101 103 349 346 345 469 565 457 452 271 3788
PARAINFLUENZA 3 6 10 4 6 2 4 1 0 1 2 0 39
PENDING 1 0 0 0 0 0 0 0 0 0 0 0 1
RHINOVIRUS 1 2 0 0 0 0 0 0 0 0 0 0 3
RSV 0 0 0 0 0 0 0 0 0 2 3 5 10
Total 268 120 127 117 404 414 425 549 651 521 502 302 4,400
Table 7. Distribution of Influenza A Virus Isolate by Strain
(Philippines, January 1 to December 30, 2007 (N=264
INFLUENZA A Total
INFLUENZA A 10
INFLUENZA A A/New Caledonia/20/90(H1N1)-like & ADENOVIRUS 1
INFLUENZA A A/New Caledonia/20/99(H1N1)-like 163
INFLUENZA A A/New Caledonia/20/99(H1N1)-like & HSV-1 1
INFLUENZA A A/New York/55/2004(H3N2)-like 86
INFLUENZA A A/New York/55/2004(H3N2)-like & ADENOVIRUS 1
INFLUENZA A A/New York/55/2004(H5N2)-like 1
INFLUENZA A A/New York/55/2004-like 1
Total 264
Pamantasan Ng
• Two classes
– Adamantanes – rimantadine and amantadine
• Currently not recommended for use due to
resistance among circulating influenza A viruses
– Neuraminidae inhibitors
• Oseltamivir and zanamivir
• Can be used for both prevention and for
treatment
Pamantasan Ng
THANK
YOU