Pamantasan Ng Lungsod Ng Maynila –College of Medicine 2008-2009

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(

Country Cases Deaths Date of Information Sources

Cambodia 20,000 38 Sep. [1]
Costa Rica 19,000 1 7 Sep. [2]
India, (West Bengal) 90,000 1,500 Sep. [3]
Indonesia 80,837 1,099 Jan. 2006 [4]
Malaysia 32,950 83 1 Nov. [5]
Martinique 6,000 2 26 Sep. [6]
Philippines 21,537 280 2 Oct. [7]
Singapore 12,700 19 22 Oct. [8]
Sri Lanka 3,000 - 16 Sep. [9]
Thailand 31,000 58 Sep. [10]
Vietnam 20,000 28 4 Oct. [11]
Pakistan 4,800 50 11 Dec 2006. [12]
Total† 232,724 16,673 — —
†
For listed countries only . World Health Organization estimates that there may be 50 million cases of dengue infection
worldwide each year
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
GEOGRAPHIC DISTRIBUTION

Worldwide Dengue distribution 2006

RED - Epidemic dengue BLUE – Aedes egypti
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
BREEDING SITES
 Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Dengue Virus

Causes dengue and dengue hemorrhagic fever

Is an arbovirus

Transmitted by mosquitoes

Composed of single-stranded RNA

(Has 4 serotypes (DEN-1, 2, 3, 4

Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Dengue Viruses
 Each serotype provides specific lifetime immunity,
and short-term cross-immunity

 All serotypes can cause severe and fatal disease

 Genetic variation within serotypes

 Some genetic variants within each serotype appear to

be more virulent or have greater epidemic potential
 Pamantasan Ng Lungsod Ng Transmission of Dengue
Maynila – College of Medicine
2008-2009 Virus
byAedes aegypti

MOSQUITO FEEDS MOSQUITO REFEEDS

acquires virus acquires virus
Extrinsic Intrinsic

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

 Lives around human

habitation

 Lays eggs and produces

larvae preferentially in
artificial containers
 Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Dengue

Undifferentiated Classical Dengue Dengue Hemorrhagic

fever Fever Fever

Fever, Headache, Abrupt onset of Fever &

Retroorbital Pain, myalgia
Severe Myalgia Increasing prostration
“Break-bone fever” Severe headache,
Macular rash at the dizziness, photophobia
trunk, spreading to the abdominal & chest pain
extremities & face Conjunctival suffusion
Epistaxis & scattered Petechiae
petechiae Borderline hypotension

Dengue Shock Syndrome

 Pamantasan Ng Lungsod Ng
Maynila – College of Medicine Warning Signs for Dengue Shock
2008-2009

: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 •

Evidence of bleeding in skin or other sites •

Hydration status •

–Evidence of increased vascular permeability •

pleural effusions, ascites

Tourniquet test •
 Tourniquet Test
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Inflate blood pressure cuff to a •

point midway between systolic and
diastolic pressure for 5 minutes

Positive test: 20 or more petechiae •

(per 1 inch2 (6.25cm2

Pan American Health Organization: Dengue and Dengue Hemorrhagic

Fever: Guidelines for Prevention and Control. PAHO: Washington,
:D.C., 1994
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009 DIAGNOSIS

Laboratory Tests in Dengue Fever

Clinical laboratory tests •
CBC--WBC, platelets, hematocrit –
Albumin –
Liver function tests –
Urine--check for microscopic hematuria –

Dengue-specific tests •
Virus isolation –
Serology –
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Laboratory Methods for

Dengue Diagnosis

Virus isolation to determine •

serotype of the infecting virus

IgM ELISA test for serologic •

diagnosis
 Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009

Diagnostic Tests
Virus isolation is the gold standard •

RT-PCR requires standardization •

IgM capture ELISA detects primary •

or secondary infections

Rapid tests includes lateral flow tests •

for dengue antibodies or antigens
TDR/WHO amd PDVI
October 2004
Pamantasan Ng Lungsod Ng
Maynila – College of Medicine
2008-2009
Dengue Fever
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

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

Endemic with estimated incidence of 25 clinical infection per 100,000

population

Significant outbreaks in Nicaragua, Brazil, India, Malaysia & USA

Large clusters of cases were noted following flooding as a result of

excessive rainfall

Human infection is either direct or indirect contact with the urine of an

infected animal, higher in warm-climate countries
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
Chain of Transmission
:Animal Species
Rodents
Cattles
Domestic animals

: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

Infected Urine & Excreta

 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
PATHOGENESIS

Adhesion to Cell Surfaces

and Cellular Toxicity
LEPTOSPIRES

PORT
OF Small Blood Vessel –vasculitis
ENTRY
Kidney –& interstitial nephritis
tubular necrosis

Conjunctiva Liver –centrilubular necrosis

Skeletal Muscles – , swelling
Mucous Membrane
focal necrosis
Mouth
Abraded Skin
Open wounds
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
CLINICAL FEATURES
Incubation Period -2 – 25 days after initial direct exposure
to the urine or tissue of an infected animal

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

2. Immune leptospiremic phase

- asymptomatic for a week, and illness recur within a few days in some
- aseptic meningitis may develop in some patient for certain duration
- however, in a few cases complication such iritis, iridocyclitis and
chorioretinitis may occur.
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
CLINICAL FEATURES
(Severe Leptospirosis (Weil’s Syndrome
1. Jaundice
2. Renal dysfunction
3. Hemorrhagic diasthesis
-Infection is associated with serovars L. icterohemorrhagiae and copenhagen
-Within 4 – 9 days, jaundice and vascular dysfunction generally develop.
-Renal failure within 2-3 weeks after, however, reversible if attended
-Pulmonary involvement with cough, dyspnea, chest pain and blood- stain sputum
-Hemorrhagic manifestations e.g. epistaxis, petechiae, purpura and eechymoses
GI bleeding, adrenal and subarachnoid hemorrhage are seen
-Rhabdomyolysis, myocarditis, CHF, cardiogenic shock, ARDS, and multi-organ
failure are seen
 Pamantasan Ng
Lungsod Ng Maynila
LABORATORY & RADIOLOGIC
College of Medicine
2008-2009 FINDINGS

URINALYSIS -urine sediments changes leokocytes, erythrocytes, hyaline or granular

casts, with mild proteinuria

ESR- elevated (anicteric leptospirosis) peripheral leukocyte count range from 3,000 to
Ul with left shift; (Weil’s Syndrome) marked leukocytosis/26,000

THROMBOCYTOPENIA- in about 50% of patients implying renal failure

LIVER ENZYMES - are noted to be elevated up to up to 200U/L (alkaline phosphatase
and aminotransferase)

PROTHROMBINE TIME - is prolonged in Weil’s however can be corrected by Vit K

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

 Seroconversion or rise in antibody titer in MAT

Presumptive
 MAT with antibody titer of >1:100

 Positive macroscopic slide agglutination test

 Presence of compatible clinical illness
 DIAGNOSIS
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

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

ENZYME-LINK IMMUNOASSAY ( ELISA )

- use to detect IgM antibodies for diagnosis of human leptospira infection
- useful towards detection of serovar-specific antibodies for detection of infection
in food animals, detection of serovar pomona and hardjo infection in cattle
- IgM-specific dot-ELISA was developed and use to detect IgG and IgA anibodies
and shown to be sensitive

MACROSCOPIC SLIDE AGGLUTINATION TEST

used for detection of 12 serovars for rapid screening of sera from humans & animals -
- a new commercial slide agglutination assay was found to be as sensitive and
specific as an IgM-ELISA while remaining reactive for a shorter time after recovery
 DIAGNOSIS
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

INDIRECT HEMAGGLUTINATION ASSAY ( IHA )

- use to detect both IgM and IgG antibodies
- it was developed at CDC and shown to have a sensitivity of 92% and a specificity
of 95% for serological diagnosis of leptospirosis

(MICROCAPSULE AGGLUTINATION TEST (MCAT

using a synthetic polymer in place of RBC and has been extensively evaluated in -
Japan and China
more sensitive than MAT and IgM-ELISA in acute phase samples -
this is a direct agglutination method -

( POLYMERASE CHAIN REACTION ( PCR

use for detection of Leptospiral DNA, more sensitive than culture -
has been used to distinguish pathogenic from non-pathogenic serovars -
 DIAGNOSIS
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

CULTURE OF THE ORGANISM

- leptospire can be detected from blood and CSF during the first 10 days of illness
st
weekwhile in urine for several weeks beginning within the 1 -
cultures may become positive after 2 to 4 weeks ranging from 2 weeks to 4 months -
- sometimes urine culture remain positive for months or years from the start of illness
-
 TREATMENT
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

Mild Cases of Leptospirosis

Oral Tetracycline, Doxycycline, Ampicillin and Amoxycillin -

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

Mortality: 1.5 – 2.7 million death

P. Falciparum

Global burden: 42,800,000 Disability-adjusted

life years

40% of mankind residing in endemic malarial

zone

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

Road traffic accidents 0.60 2.1

 Malaria
Situation
 63 malaria endemic provinces
 16 malaria – free provinces
 12 million at risk of malaria
 2005 data:
 46,342 malaria cases
 150 malaria deaths
 Morbidity Rate: 55/100,000
 Mortality Rate: 0.17/100,000
 2006 data:
 33,852 malaria cases (↓27%)
 89 deaths (↓40%)
 Morbidity Rate: 40/100,000
 Mortality Rate: 0.10/100,000
GEOGRAPHICAL DISTRIBUTION OF MALARIA,
PHILIPPINES
(Based on 5-year Ave, 2001 – 2005)
Category A Provinces
• 9 provinces (from 26 provinces)
• Ave. no. of malaria cases:
> 1,000 cases
Category B Provinces
• 23 provinces (from 22 provinces)
• Ave. no. of cases:
100 - < 1,000 cases
Category C Provinces
• 31 provinces (from 18 provinces)
• Ave. no. of cases: < 100 cases

Category D Provinces
• 16 provinces (from 13 provinces)
• 16 provinces remain malaria-free
status

Source: Malaria Control Program, 2006

 GEOGRAPHICAL
DISTRIBUTION OF MALARIA
CASES, PHILIPPINES
2001 - 2005
Category A Provinces
• 9 provinces
• 4 (Luzon)
• 5 (Mindanao)
• 8 GF/RBM project sites
Apayao (A)
Cagayan (A)
Palawan (A)
Isabela (A)
Sulu (A)
Tawi-tawi (A)
Davao del Sur (A)
Agusan del Sur (A)
Sultan Kudarat (B)
GEOGRAPHICAL DISTRIBUTION OF
MALARIA CASES, PHILIPPINES
PHILIPPINES, 2001 - 2005
Category B Provinces
• 23 provinces
• 16 GF/RBM proj site; 7 still in Cat. B
• 10 (Luzon); 13 (Mindanao)

 Sarangani (A)  Nueva Vizcaya (B)

 Kalinga (A)  Aurora (B)
 Davao del Norte (A)  Maguindanao (B)
 Mindoro Occ. (A)  North Cotabato (B)
 Agusan del Norte (A)  Mindoro Oriental (B)
 Zambales (A)  South Cotabato (B)
 Quirino (A)  Rizal (B)
 Surigao del Sur (A)
 Compostela Valley (A)
 Davao Oriental (A)
 Zamboanga del Sur (A)
 Basilan (A)
 Mt. Province (A)
 Bukidnon (A)
 Misamis Oriental (A)
 Quezon (A)
GEOGRAPHICAL DISTRIBUTION OF MALARIA
CASES
PHILIPPINES, 2001 - 2005
Category C Provinces
• 31 provinces
2 Cat. A prov. are now in Cat. C
14 Cat. B are now in Cat. C
15 are still in Cat. C
20 (Luzon); 5 (Visayas); 6 (Min)

Ifugao (A) Negros Oriental (C)

Zamboanga Sigubay (A) Antique (C)
Abra (B) Ilocos Sur (C)
Ilocos Norte (B) Batangas (C)
Tarlac (B) Misamis Occidental
Zamboanga del Norte (B) (C)
Bulacan (B) Batanes (C)
Pangasinan (B) Negros Occidental
Nueva Ecija (B) (C)
Camarines Norte (B) Pampanga (C)
Romblon (B) La Union (C)
Bataan (B)
Lanao del Norte (B)
Lanao del Sur (B)
Laguna (B)
Camarines Sur (B)
GEOGRAPHICAL DISTRIBUTION OF
MALARIA CASES
PHILIPPINES, 2001 - 2005
Category D Provinces
• 16 provinces + 6 provinces *
Benguet *Albay
Cavite *Sorsogon
Masbate *Marinduque
Cebu *Eastern Samar
Bohol *Western Samar
Catanduanes *Surigao del
Aklan Norte
Capiz
Guimaras
Siquijor
Biliran
Iloilo
Northern Leyte
Southern Leyte
Northern Samar
Camiguin
 LIFE CYCLE OF MALARIA

Three Components of the Malaria Life Cycle

• Anopheles mosquito must be present
• Humans must be present
• Parasites must be present
Factors That Determine The
Occurrence of Malaria

 CLIMATE

 ANOPHELES MOSQUITOES

 HUMAN HOSTS

 PARASITES

 Other rare conditions

a. Congenital Malaria
b. Transfusion Malaria
c. Needle-sharing
CLIMATE

 Rainfall either can enhance breeding sites

or flushed
and destroyed due to excessive rains.

 Warmer ambient temperature (25 C or 77F)

shorten
the duration of extrinsic cycle thus
increases the
chances of transmission

 Affects human behavior where people

tends to sleep
outdoors and discourage from using bed
nets
ANOPHELES MOSQUITOES
Species Biological Characteristics

1. “Anthropohilic”- female anoph. prefer to get

their blood meals from humans
2. “Zoophilic” – prefer blood meals from animals
3. “Endophagic” – some species tend to bite
indoors
4. “Exophagic” – outdoor biting
5. “Endophilic” – some species tend to rest after a
blood meal indoors
6. “Exophilic” – while others rest outdoors
7. “Insecticide resistance” an important biologic
factor that increases transmission rates
HUMAN FACTORS

BIOLOGIC CHARACTERISTICS
Genetic Factors
• Sickle cell traits – heterozygotes for
abnormal
hemoglobin genes Hbs protective from
P. Falciparum

Duffy negative blood groups – resistant

to infection
from P. Vivax

HLA complex – plays a role in control of

immune
BIOLOGIC CHARACTERISTICS
Acquired Immunity
- “Semi-immunity” of individuals with
repeated
attacks develops a partially
protective
immunity
- “Anemia” (6-24 mos) children in
Kenya
- “Maternal antibodies” with
protection against
P. Falciparum

Pregnancy decreases immunity against

many
PARASITE
4 Global Malarial Parasites
1. Plasmodium Falciparum
2. Plasmodium Vivax
3. Plasmodium Ovale
4. Plasmodium Malariae

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

QUARTAN MALARIAL NEPHROPATHY

BURKITT’S LYMPHOMA & EBV INFECTION
 (BLOOD SMEAR MALARIA (BSM

THIN BLOOD SMEAR

blood smear must be air-dried, fixed, stained and the red cells in -
the tail of the film should be read under oil immersion

the level of parasitemia is expressed as the number of parasitized -

erythrocytes among 1000 cells as a basis for parasite count
 (BLOOD SMEAR MALARIA (BSM

THICK BLOOD SMEAR

- blood smear dried, stained without fixing

- has the advantage of concentrating the parasite (by 20-40 fold compared
with the thin blood film) thus increasing
diagnostic sensitivity
- both parasites and white cells are counted and the number of parasites
per unit volume is calculated from the total leukocyte count
- a white cell count of 8,000/ul is assumed
- a phagocytized malarial pigment inside peripheral blood monocyte and
polymorphonuclear leukocytes gives a clue of recent infection despite
absence of parasites
DIAGNOSIS
DEMONSTRATION OF THE PARASITE
P. Falciparum – Thin Film

Ring form Trophozoite PMN & Tropozoite Schizont Gametocyte

Thick Film

P Falci-Trophozoite Gametocyte P. vivax-tropo P. vivax-schizont Gametocyte

 CHARACTERISTICS OF
PLASMODIUM SPECIES

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

QUININE Acts mainly on trophozoite blood stage; kills

gametocytes of P vivax, ovale, malariae; no
action on liver stage; effective against severe
complicated falciparum malaria

MEFLOQUINE As for quinine but acts slightly earlier in

asexual cycle

CHLOROQUINEAs for quinine

TETRACYCLINE Weak antimalarial activity, should not be used
alone

HALOFANTRINEAs for quinine

 ANTIMALARIAL AGENTS

ARTEMISINBroader stage specificity and more rapid than

Artemether, Artesunateother drugs, no action on liver stage
PYRIMETHAMINE For blood stage, acts mainly on mature forms,
as causal prophylactic

PRIMAQUINE Radical cure; eradicates hepatic form of P.

vivax and P. ovale; kills gametocyte of P.
falciparum

PROGUANILCausal prophylactic, not used alone for tx

ATOVAQUONEActs mainly on trophozoite blood stage
LUMEFANTRINEAs for quinine
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009
 ABCs of Influenza and Pandemic
Update

Photo: Cynthia Goldsmith

68
 Pamantasan Ng

Learning Objectives
Lungsod Ng Maynila
College of Medicine
2008-2009

Describe the characteristics of influenza

infection in humans

Understand different types of influenza

viruses and how they can infect humans
and animals

Describe the ways that influenza viruses

can change or mutate
 Pamantasan Ng

Learning Objectives Lungsod Ng Maynila

College of Medicine
2008-2009

Describe the epidemiology of influenza

and contrast pandemic influenza with
seasonal and avian influenza outbreaks

Understand the recent history of avian

influenza outbreaks in humans

Describe the epidemiology and clinical

characteristics of H5N1 in humans
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

Seasonal Influenza Pandemic Influenza

Preparedness Preparedness
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

Seasonal Influenza Infection

in Humans
 Pamantasan Ng

Key Characteristics
Lungsod Ng Maynila
College of Medicine
2008-2009

Influenza is arespiratory infection

:Transmission
Person-to-person transmission

Primarily through contact with respiratory

droplets

Transmission from objects (fomites) possible

 : Transmission
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

Limited studies, varying interpretations

Contact, droplet, and droplet nuclei

(airborne) transmission all likely occur

Relative contribution of each

unclear

Droplet thought most important

Coughing, sneezing, talking

Most studies either

Animals or human experiments
under artificial conditions

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

Key Characteristics Lungsod Ng Maynila

College of Medicine
2008-2009

:Communicability
Viral shedding can begin 1 day
before symptom onset

Peak shedding first 3 days of

illness

Correlates with temperature

Subsides usually by 5-7th day

in
adults can be 10+ days in
children

Infants, children and the

immunocompromised may
 Pamantasan Ng
Lungsod Ng Maynila

Key Characteristics College of Medicine

2008-2009

: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

:Clinical Diagnosis College of Medicine

2008-2009

:Clinical symptoms non-specific

 Symptoms overlap with many pathogens

 Coupling with laboratory data to verify diagnosis

 Even at peak of seasonal influenza, nationally,

about
30% specimens tested for influenza are positive
 :Clinical Illness
Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

Abrupt onset

 Fever and constitutional symptoms: body aches, headaches,

fatigue

 Cough, rhinnitis, sore throat

 GI symptoms and myositis more common in young children

 Sepsis-like syndrome in infants

 Complications: viral and bacterial pneumonia, febrile

seizures, cardiomyopathy, encephalopathy/encephalitis,
worsening underlying chronic conditions
 Pamantasan Ng

:Laboratory Test Lungsod Ng Maynila

College of Medicine
2008-2009
Viral culture
Gold standard but results take 7+ days usually
Influenza isolates for yearly vaccine development

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

Table 1. ILI Cases by Region

(Philippines, January 1 to December 31, 2006 (N=4,400

Region Province Number of Cases Percent

ARMM Lanao del Sur - 1 0.0
CAR Benguet - 453 5.7
I La Union, Pangasinan - 6 0.1
III Nueva Ecija, Pampanga - 530 11.2
IV Rizal - 19 0.3
IX Zamboanga del Sur - 288 4.8
NCR Metro Manila - 2,042 53.0
V Albay, Camarines Sur - 367 8.8
VII Bohol, Cebu - 473 12.1
VIII Southern Leyte - 1 0.0
X ,Bukidnon, Misamis Occidental - 220 3.9
Misamis Oriental
Total 4,400 100
 ILI Cases by Age Group
Philippines, January 1 to December 30, 2006 (N=4,400)

Female Male

>50 32 18

40-49 36 15

30-39 63 27

Agegroup 20-29 91 43

10-19 224 237

5-9 516 545

1-4 821 871

<01 411 450

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

:Vaccination Lungsod Ng Maynila

College of Medicine
2008-2009

Influenza vaccine. is the best prevention for seasonal influenza

Inactivated viruses in the vaccine developed from three circulating

(strains (generally 2 Type A and 1 Type B strain
Therefore, seasonal “flu shot” only works for 3 influenza subtypes
and
.will not work on pandemic strains

Live, intranasal spray vaccine for healthy non-pregnant persons

years 5-49

Inactivated, injectable vaccine for persons 6 months and older

 Pamantasan Ng
Lungsod Ng Maynila

:Antiviral Medications College of Medicine

2008-2009

• 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

:Other measures Lungsod Ng Maynila

College of Medicine
2008-2009

• Infection control measures

– Used mostly in health care settings during
seasonal influenza
– Include cohorting, use of droplet precautions
(masks, gowning, gloves), limiting exposures
(e.g. no new admissions), having ill workers
stay home, etc.
– Generally not used for seasonal influenza on
a community-level
 Pamantasan Ng
Lungsod Ng Maynila
College of Medicine
2008-2009

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