dengue, leptospirosis, malaria, influenze
TRANSCRIPT
Pamantasan Ng Lungsod Ng Maynila – College of Medicine 2008-2009
LEPTOSPIROSIS
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009 DENGUE
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
CountryCasesDeathsDate of InformationSources
Cambodia20,00038Sep.[1]
Costa Rica19,00017 Sep.[2]
India, (West Bengal)90,0001,500Sep.[3]
Indonesia80,8371,099Jan. 2006[4]
Malaysia32,950831 Nov.[5]
Martinique6,000226 Sep.[6]
Philippines21,5372802 Oct.[7]
Singapore12,7001922 Oct.[8]
Sri Lanka3,000-16 Sep.[9]
Thailand31,00058Sep.[10]
Vietnam20,000284 Oct.[11]
Pakistan4,8005011 Dec 2006.[12]
Total†232,72416,673——†For listed countries only . World Health Organization estimates that there may be 50 million cases of dengue infection
worldwide each year
2005 (dengue outbreak(
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009GEOGRAPHIC DISTRIBUTION
Worldwide Dengue distribution 2006RED - Epidemic dengue BLUE – Aedes egypti
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009BREEDING SITES
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 Maynila – College of Medicine
2008-2009
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
HUMAN # 1 HUMAN # 2
Illness IllnessDAYS
Viremia Viremia
0 5 8 12 16 20 24 28
acquires virusMOSQUITO FEEDS MOSQUITO REFEEDS
acquires virus
Extrinsic
Incubation
Period
Intrinsic
Incubation
Period
Transmission of Dengue Virus
by by Aedes aegyptiAedes aegypti
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
4. Virus released and circulates in blood
3. Virus infects white blood cells and lymphatic tissues
2. Virus
replicates in target organs
1. Virus transmitted to human in mosquito saliva
1
2
3
4
Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 1)of Dengue Virus (Part 1)
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
7. Virus replicates in salivary glands
6. Virus replicates in mosquito midgut and other organs, infects salivary glands
5. Second mosquito ingests virus with blood
6
7
5
Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 2)of Dengue Virus (Part 2)
Dengue transmitted byDengue transmitted by infected female infected female mosquitomosquito
Primarily a daytimePrimarily a daytime feederfeeder
Lives around humanLives around human habitationhabitation
Lays eggs and producesLays eggs and produces larvae preferentially inlarvae preferentially in artificial containersartificial containers
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
Dengue
Undifferentiatedfever
Classical DengueFever
Dengue HemorrhagicFever
Fever, Headache, Retroorbital Pain, Severe Myalgia “Break-bone fever” Macular rash at the trunk, spreading to the extremities & face Epistaxis & scattered petechiae
Abrupt onset of Fever & myalgia Increasing prostration Severe headache, dizziness, photophobia abdominal & chest pain Conjunctival suffusion Petechiae Borderline hypotension
Dengue Shock Syndrome
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
Initial WarningSignals:
•Disappearance of fever •Drop in platelets
•Increase in hematocrit
Four Criteria for DHF: •Fever
•Hemorrhagic manifestations •Excessive capillary
permeability ≤ •100,000/mm3 platelets
When Patients DevelopDSS:
•3 to 6 days after onset ofsymptoms
Alarm Signals: •Severe abdominal pain
•Prolonged vomiting •Abrupt change from fever
to hypothermia •Change in level of
consciousness)irritability or somnolence(
Warning Signs for Dengue Shock
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
•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)
Severity Grading of DHF
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
•Blood pressure
•Evidence of bleeding in skin or other sites
•Hydration status
•Evidence of increased vascular permeability – pleural effusions, ascites
•Tourniquet test
Clinical Evaluation in Dengue
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)
Tourniquet Test
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
•Clinical laboratory tests –CBC--WBC, platelets, hematocrit
–Albumin –Liver function tests
–Urine--check for microscopic hematuria
•Dengue-specific tests –Virus isolation
–Serology
Laboratory Tests in Dengue Fever
DIAGNOSIS
Laboratory Methods forDengue Diagnosis
•Virus isolation to determineserotype of the infecting virus
•IgM ELISA test for serologicdiagnosis
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
•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
Diagnostic Tests
TDR/WHO amd PDVIOctober 2004
Pamantasan Ng Lungsod Ng Maynila – College of Medicine
2008-2009
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 LeptospirosisDescribe the etiologic agent of Leptospirosis Discuss the pathogenesis of LeptospirosisDiscuss the temporal profiles of the clinical features, including anicteric and Weil’s diseaseDiscuss the appropriate use of diagnostic tests: MAT, MCAT, IHA, ELISADiscuss 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
Chain of TransmissionPamantasan Ng
Lungsod Ng Maynila College of Medicine
2008-2009
Animal Species : Rodents
Cattles Domestic animals
Human Infections: Occupational
Direct Contact• farmers• veterinarians• abattoir workers• meat inspectors Indirect• sewers • miners • soldiers• septic tank cleaners• canal workers
Recreational water sports, swimming,
canoeing, water rafting, potholing, caving
Avocational exposures barefoot walking ,
flood swimming
Serological Classification & Groupings Hosts Serogroups
RATS L. Icterohaemorrhagiae MICE L. Ballum
DAIRY CATTLES L. Hardjo, Pomona DOGS L. Canicola
SHEEP L. Hardjo PIGS L. Pomona, Tarassovi
HUMANS L. Icterohaemorrhagiae
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Genomospecies
Serogroup
L. interrogans[pathogenic]
Australis
Autumnalis
Ballum
Bataviae
Canicola
Celledoni
Cynopteri
Djasiman
Grippotyphosa
Hebdomadis
Icterohaemorrhagiae
Javanica
Louisiana
Lyme
Manhao
Mini
Panama
Pomona
Pyrogenes
Ranarum
Sarmin
Sejroe
Shermani
Tarassovi
L. biflexa[non-pathogenic]
Andamana
Codice
Semaranga
L. borgpetersenii
L. inadai
L. noguchii
L. santarosai
L. weilii
L. kirshneri
L. meyeri
L. wolbachii
Genomospecies Serogroup
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Infected Urine & Excreta
PATHOGENESIS
PATHOGENESISPamantasan Ng
Lungsod Ng Maynila College of Medicine
2008-2009
PORT
OF
ENTRY
LEPTOSPIRES
Conjunctiva
Mucous Membrane
Mouth
Abraded Skin
Open wounds
Adhesion to Cell Surfaces
and Cellular Toxicity
Small Blood Vessel –vasculitis
Kidney – interstitial nephritis&
tubular necrosis
Liver – centrilubular necrosis
Skeletal Muscles – swelling ,
focal necrosis
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009CLINICAL FEATURES
Incubation Period - 2 – 25 days after initial direct exposure
to the urine or tissue of an infected animal
Biphasic stages Anicteric Leptospirosis
1 .Acute leptospiremic phase - - 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
2008-2009CLINICAL 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
2008-2009CLINICAL 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 College of Medicine
2008-2009
LABORATORY & RADIOLOGIC 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
26,000/Ul with left shift; (Weil’s Syndrome) marked leukocytosis
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
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
DIAGNOSIS
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
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
DIAGNOSIS
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
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
DIAGNOSIS
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
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
DIAGNOSIS
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
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
DIAGNOSIS
CULTURE OF THE ORGANISM
- leptospire can be detected from blood and CSF during the first 10 days of illness
- while in urine for several weeks beginning within the 1st week
- 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
-
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
TREATMENT
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
Low-income countries Deaths in millions % of deathsCoronary heart disease 3.29 11.4Lower respiratory infections 2.72 9.5HIV/AIDS 2.06 7.2Stroke and other cerebrovascular diseases 1.83 6.4Perinatal conditions 1.72 6.2Diarrhoeal diseases 1.58 5.2Tuberculosis 1.01 3.5Chronic obstructive pulmonary disease 0.97 3.4Malaria 0.87 3.2 Road traffic accidents 0.60 2.1
THE TOP TEN CAUSES OF DEATH (2005)WHO
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
Category A ProvincesCategory A Provinces• 9 provinces (from 26 provinces)9 provinces (from 26 provinces)• Ave. no. of malaria cases:Ave. no. of malaria cases: > 1,000 cases> 1,000 cases Category B ProvincesCategory B Provinces• 23 provinces (from 22 provinces)23 provinces (from 22 provinces)• Ave. no. of cases: Ave. no. of cases: 100 - < 1,000 cases100 - < 1,000 cases
Category C ProvincesCategory C Provinces• 31 provinces (from 18 provinces)31 provinces (from 18 provinces)• Ave. no. of cases: < 100 casesAve. no. of cases: < 100 cases
Category D ProvincesCategory D Provinces• 16 provinces (from 13 provinces)16 provinces (from 13 provinces)• 16 provinces remain malaria-free 16 provinces remain malaria-free statusstatus
GEOGRAPHICAL DISTRIBUTION OF MALARIA, GEOGRAPHICAL DISTRIBUTION OF MALARIA, PHILIPPINES PHILIPPINES
(Based on 5-year Ave, 2001 – 2005)(Based on 5-year Ave, 2001 – 2005)
Source: Malaria Control Program, 2006
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, PHILIPPINES2001 - 2005
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) Kalinga (A) Davao del Norte (A) Mindoro Occ. (A) Agusan del Norte (A) Zambales (A) Quirino (A) 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)
Nueva Vizcaya (B) Aurora (B) Maguindanao (B) North Cotabato (B) Mindoro Oriental (B) South Cotabato (B) Rizal (B)
GEOGRAPHICAL DISTRIBUTION OF MALARIA CASES
PHILIPPINES, 2001 - 2005Category 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)Zamboanga Sigubay (A)Abra (B)Ilocos Norte (B)Tarlac (B)Zamboanga del Norte (B)Bulacan (B)Pangasinan (B)Nueva Ecija (B)Camarines Norte (B)Romblon (B)Bataan (B)Lanao del Norte (B)Lanao del Sur (B)Laguna (B)Camarines Sur (B)
Negros Oriental (C)Antique (C)Ilocos Sur (C)Batangas (C)Misamis Occidental (C)Batanes (C)Negros Occidental (C)Pampanga (C)La Union (C)
GEOGRAPHICAL DISTRIBUTION OF MALARIA CASES
PHILIPPINES, 2001 - 2005
Category D Provinces• 16 provinces + 6 provinces *
Benguet *AlbayCavite *SorsogonMasbate *MarinduqueCebu *Eastern SamarBohol *Western SamarCatanduanes *Surigao delAklan NorteCapizGuimarasSiquijorBiliranIloiloNorthern Leyte Southern Leyte Northern SamarCamiguin
LIFE CYCLE OF MALARIA
Three Components of the Malaria Life Cycle
A. Anopheles mosquito must be presentB. Humans must be present C. 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
Harvest seasons drives farmers to sleep in the fields without protection fro mosquitoe bites
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
response
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 infectious diseases. Malarial infection is harmful to both mother and the unborn babies.
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
anti-malarial that are protective.
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
1 .Fever
2 .Chills
3 .Sweating
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 MALARIAHYPERACTIVE 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 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
THICK BLOOD SMEAR
BLOOD SMEAR MALARIA (BSM)
DIAGNOSISDEMONSTRATION OF THE PARASITE
Ring form Trophozoite PMN & Tropozoite Schizont Gametocyte
Thick Film
P. Falciparum – Thin Film
P Falci-Trophozoite Gametocyte P. vivax-tropo P. vivax-schizont Gametocyte
CHARACTERISTICS OF PLASMODIUM SPECIES
FINDINGS ON MICROSCOPE
P. Falciparum
P. VivaxP. OvaleP Malariae
MORPHOLOGYUsually only ring forms, banana-shaped gametocytes
Irregularly shaped large rings, enlarge erythrocytesm Shuffners dots
Infected ery- throcytes, enlarged and oval, Shuffners dot
Band or rectangular forms of trophozoites common
PIGMENTBLACKYELLOW BROWN
DARK 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
CHLOROQUINE As for quinine
TETRACYCLINE Weak antimalarial activity, should not be used alone
HALOFANTRINE As for quinine
ARTEMISIN Broader stage specificity and more rapid than Artemether, Artesunate other 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
PROGUANIL Causal prophylactic, not used alone for tx
ATOVAQUONE Acts mainly on trophozoite blood stage
LUMEFANTRINE As for quinine
ANTIMALARIAL AGENTS
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
68
ABCs of Influenza and Pandemic Update
Photo: Cynthia Goldsmith
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009Learning Objectives
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 Lungsod Ng Maynila College of Medicine
2008-2009Learning Objectives
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 InfluenzaPreparedness
Pandemic InfluenzaPreparedness
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Seasonal Influenza Infection in Humans
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Influenza is a respiratory infection
Transmission:Person-to-person transmission Primarily through contact with respiratory droplets Transmission from objects (fomites) possible
Key Characteristics
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Transmission:
Limited studies, varying interpretations
Contact, droplet, and droplet nuclei (airborne) transmission all likely occur
Relative contribution of each unclear
Droplet thought most importantCoughing, sneezing, talking
Most studies eitherAnimals or human experiments under artificial conditions
Outbreak investigationsUnclear 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 in Bukhara, Russia. By October, it had reached Tomsk and the Caucasus. 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
and mortality rate .
Pamantasan Ng 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
shed the virus longer
Key Characteristics
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
Incubation period:Time from exposure to onset of symptoms
1 to 4 days (average = 2 days)
Seasonality:In temperate zones, sharp peaks in winter
months In tropical zones, circulates year-round with
seasonal increases.
Key Characteristics
Pamantasan Ng Lungsod Ng Maynila 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 Diagnosis:
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
Clinical Illness:
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009Laboratory Test:
Viral cultureGold standard but results take 7+ days usuallyInfluenza isolates for yearly vaccine development
Point-of-care testsGenerally 70+% sensitive, 90+% specificCan provide results <30 minutes
ImmunofluorescenceRequires intact cells and laboratory skill/experience
SerologyMust used paired serum samples>2 week delay for result
RT-PCRMost sensitiveBecoming more widely available
Influenza-Like Illness Reported at the Sentinel Sitesof National Influenza Surveillance System, 2006
Table 1. ILI Cases by Region
Philippines, January 1 to December 31, 2006 (N=4,400)
RegionProvince 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)
32
36
63
91
224
516
821
411
18
15
27
43
237
545
871
450
>50
40-49
30-39
20-29
10-19
5-9
1-4
<01
Agegroup
02004006008001000 0 200 400 600 800 1000
Female Male
No. of Cases in Thousands
Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec17 6 12 4 23 5 5 4 8 4 1 97 3 2 2 1 5 2 0 0 2 6 56 3 2 4 4 2 1 1 0 4 4 13 0 0 0 21 53 57 53 32 20 16 90 0 0 0 0 1 11 21 46 31 18 2
230 100 101 103 349 346 345 469 565 457 452 2713 6 10 4 6 2 4 1 0 1 2 01 0 0 0 0 0 0 0 0 0 0 01 2 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 2 3 5
268 120 127 117 404 414 425 549 651 521 502 302
3788
Table 5. Distribution of Influenza Virus Isolates by Month
INFLUENZA BNEGATIVEPARAINFLUENZA
Virus Isolate ResultADENOVIRUS
HSV-1INFLUENZA A
ENTEROVIRUS
10
Total 4,400
13
PENDINGRHINOVIRUSRSV
39
264130
Total983532
Philippines, January 1 to December 31, 2006 (N=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 A10
INFLUENZA A A/New Caledonia/20/90(H1N1)-like & ADENOVIRUS1
INFLUENZA A A/New Caledonia/20/99(H1N1)-like163
INFLUENZA A A/New Caledonia/20/99(H1N1)-like & HSV-11
INFLUENZA A A/New York/55/2004(H3N2)-like86
INFLUENZA A A/New York/55/2004(H3N2)-like & ADENOVIRUS1
INFLUENZA A A/New York/55/2004(H5N2)-like1
INFLUENZA A A/New York/55/2004-like1
Total264
Pamantasan Ng 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 5-49 years
Inactivated, injectable vaccine for persons 6 months and older
Vaccination:
Pamantasan Ng Lungsod Ng Maynila 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
Antiviral Medications:
Pamantasan Ng 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
Other measures:
Pamantasan Ng Lungsod Ng Maynila College of Medicine
2008-2009
THANKYOU
QUIZ NEXT WEEK