Dengue, Leptospirosis, Malaria, Influenze

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(

http://en.wikipedia.org/wiki/Cambodia

http://www.adnki.com/index_2Level.php?cat=Security&loid=8.0.215931004&par=0

http://en.wikipedia.org/wiki/Costa_Rica

http://www.alertnet.org/thenews/newsdesk/N07212679.htm

http://en.wikipedia.org/wiki/India

http://en.wikipedia.org/wiki/West_Bengal

http://www.iht.com/articles/ap/2006/10/02/asia/AS_GEN_India_Dengue_Outbreak.php

http://en.wikipedia.org/wiki/Indonesia

http://www.bernama.com/bernama/v3/news_lite.php?id=176076

http://en.wikipedia.org/wiki/Malaysia

http://thestar.com.my/news/story.asp?file=/2005/11/2/nation/12486682&sec=nation

http://en.wikipedia.org/wiki/Martinique

http://www3.cnn.com/2005/WORLD/americas/09/26/degnue.island.ap/

http://en.wikipedia.org/wiki/Philippines

http://news.inq7.net/breaking/index.php?index=2&story_id=53192

http://en.wikipedia.org/wiki/2005_dengue_outbreak_in_Singapore

http://www.moh.gov.sg/corp/publications/listmore.do?id=pub_title_commdisease&cid=pub_newsletters

http://en.wikipedia.org/wiki/Sri_Lanka

http://mdn.mainichi-msn.co.jp/international/news/20050916p2g00m0in014000c.html

http://en.wikipedia.org/wiki/Thailand


http://en.wikipedia.org/wiki/Vietnam

http://www.thsv.org/news_details.aspx?newsID=883

http://en.wikipedia.org/wiki/Pakistan


http://en.wikipedia.org/wiki/World_Health_Organization


2008-2009GEOGRAPHIC DISTRIBUTION

Worldwide Dengue distribution 2006RED - Epidemic dengue BLUE – Aedes egypti


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)


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


2008-2009


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


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)


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


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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


2008-2009


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


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•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


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•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


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:


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•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


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•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


2008-2009


2008-2009

Dengue Fever

Pamantasan Ng Lungsod Ng Maynila College of Medicine

2008-2009


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


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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


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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


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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


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



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.



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


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


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


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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


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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


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


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

-


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 erythrocytes, 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


2008-2009

http://en.wikipedia.org/wiki/Image:EM_of_influenza_virus.jpg

68

ABCs of Influenza and Pandemic Update

Photo: Cynthia Goldsmith




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



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


2008-2009

Seasonal InfluenzaPreparedness

Pandemic InfluenzaPreparedness



2008-2009

Seasonal Influenza Infection in Humans



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


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



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 .



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


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


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:


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:


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


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:



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:


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:


2008-2009

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Dengue, Leptospirosis, Malaria, Influenze