Lecture 54 - 3rd Asessment - Malaria

Learning Objectives  Must     

(Malaria)

know about:

Endemic countries & Importance to Kuwait Life Cycles of P. falciparum and P. vivax Diagnosis Pathogenesis of Severe Malaria Prevention

 Should

know:

 Drug

Resistant Malaria  Treatment & Prophylaxis

Case 1 A 29-year old Indian male presented with fever (39C) with rigors for 5 days. •He felt lethargic and weak •

•Physical examination showed splenomegaly •He visited India 6 months ago and had fever for 5days.

oMicroscopy of Blood smear showed

Clinical Queries • What is your provisional diagnosis? • What’s the etiological agent of this • infection? How and where did he get the infection?

• What’s the significance of travel to India?

• How would you diagnose this infection?

• Why the symptoms reappeared 6 months after his visit ? • How would you manage this patient?

Case 2 A 25-year old Kuwaiti male presented with fever with chills 39C for 4 days. •He felt lethargic and weak; he was slightly anemic •

•Physical examination was normal •He visited Sri Lanka 2 weeks ago oMicroscopy of Blood smear showed

Case 2 The patient was given a standard chloroquine therapy: Day 1: Chloroquine (10 mg/kg) 600 mg & 300 mg after 6 hrs Day 2, 3: Chloroquine (5 mg/kg)

300 mg/day

Microscopy of Blood smear done on the 3rd day was positive for malarial parasite

Case 2 Day 4: Quinine 10 mg/day plus Oxytetracycline 250 mg 8 hrly

for 1 week

Blood film became negative on the 6th day

Clinical Queries • What is your provisional diagnosis? • What’s the etiological agent of this • infection? How and where did he get the infection? • How would you diagnose this infection?

• How would you manage this patient?

• Why the drug was changed on the 4th day? • How you would you follow up the patient?

Malaria  Tropical 

(P. falciparum, vivax, ovale, malariae)

& subtropical, ME. Africa

Indigenous in 102 countries

 Vector:

Female Anopheles sp  Falciparum is the deadliest 1 million children die in Africa/year

 Life – –

cycle:

Exoerythrocytic Cycle Erythrocytic Cycle

Geographical Distribution

Malaria Situation in Kuwait No Transmission of Malaria Infection Vector:

Anopheles stephensi. Anopheles pulcherrimus

Malaria Cases: * * * *

>800 cases reported/Year All are imported cases 2/3rd are P. vivax & 1/3rd P. Falciparum >80% cases are in Expatriates from Asian countries

Malaria Vector Female Anopheles sp.

• Favorable Environment - Optimum Temperature - Optimum Humidity • Susceptible Host

Malaria in Kuwait

Malaria Situation in Kuwait No Transmission of Malaria Infection Vector:

Anopheles stephensi. Anopheles pulcherrimus

Malaria Cases: * * * *

>800 cases reported/Year All are imported cases 2/3rd are P. vivax & 1/3rd P. Falciparum >80% cases are in Expatriates from Asian countries

Trucks, tractor-trailers and buses have • Blind spots the same size as cars. • Mirrors that eliminate blind spots. • Much smaller blind spots than cars. • Much larger blind spots than

Malaria

Life Cycle

Malaria

Ring

P. vivax

Trophozoite

Schizont

Malaria

P. falciparum

No mature stages are seen in peripheral blood

Malaria

P. malariae

P. ovale

Malaria

24-48 hrs

Fever

48 hrs

72 hrs

Malaria

Pathology

Varies with the species of parasite Infected Falciparum malaria: Fever, Hemolysis, Anemia, Occlusion of cerebral vessels, Cerebral malaria Vivax malaria: Relapses are common due to latent liver stages ‘Hypnozoites’.

Malaria

Pathology

Relapse: Clinical attack due to reactivation of latent stages ‘hypnozoites’ after complete clearance of erythrocytic stages P. vivax & P. ovale

Recrudescence: Renewed clinical attack due to survival of erythrocytic stages in submicroscopic levels P. falciparum & P. malariae

Malaria

Pathology

Falciparum malaria

Hepatosplenomegaly

Malaria

Pathology

Falciparum malaria

Anaemia

Malaria

Pathology

Severe Falciparum Malaria

Liver damage

Kidney damage

Malaria

Pathology

Severe Falciparum Malaria

Retinal haemorrhage

Malaria

P. falciparum

No mature stages are seen in peripheral blood

Thick film

Thin film

Ring Stage

Gametocyte

Malaria

Pathology

Cerebral Malaria

Pathogenesis of Cerebral Malaria Exact Mechanism(s) Not Known 

 Knobs on the mature stages

  Adherence to the endothelial cells   Rosetting

Increased production of TNF­α  Upregulation of ICAM­1      Production of Nitric oxide 

Malaria

Pathology Cerebral Malaria

Host receptors: Thrombospondin (TSP) Leucocyte Diff. Ag. (CD36) Intercellular Adhesion Molecule-1 (ICAM-1)

Malaria

Pathology

Cerebral Malaria RBC Ligands:    

Pf HRP-1 Pf EMP 1 Pf 332 Modified BAND 3    

Malaria

Pathology Cerebral Malaria

Malaria

Pathology Cerebral Malaria

Malaria

Diagnosis

1. Travel History 2. Blood film: Thick & Thin

3. Antigen testing 4. PCR

??

Malaria

Immunity vs Resistance

Immunity: 2. Natural Immunity Infants (1st 4 months)

5. Acquired Immunity 6. Premunition 7. Anti-disease immunity Resistance (Relative resistance): • Sickle-cell trait • G6PD deficiency • Duffy antigen negative (P. vivax)

Malaria

Treament

1. Suppressive Clinical Chloroquine

2. Radical Treatment: P. vivax, P. Ovale Primaquine

3. Chloroquine Resistance Mefloquine

4. In Pregnancy Mefloquine

5. Infants & Children Chloroquine, Mefloquine

Malaria Challenge

 Emergence of Drug Resistant P. falciparum Strains  Development of Malaria Vaccine

Drug Resistant Malaria Geographical Distribution

   Malaria Vaccines 

Pre-erythrocytic Stage vaccines: CS protein: (NANP) 40-66 kDa



Asexual Stage Vaccines: Merozoite Surface Proteins: MSP-1 (195 kDa), MSP-2 (45 kDa)



Transmission Blocking Vaccines Pfs25



25 kDa

SPf66 NANP [Pf83 (MSA-1), Pf35, Pf55] NANP

Malaria

Prevention

1. Mosquito control 2. Bed nets 3. Insecticide spray 4. Treatment 5. Chemoprophylaxis

Malaria Chemoprophylaxis

 Take Chemoprophylaxis according to Travel Central America, Middle East: Southeast Asia, Africa:

Chloroquine Mefloquine

 Start Before Travel

 Continue During & After Travel Chloroquine and Proguanil are safe for use in pregnancy

Passing is prohibited • Within 100 feet of a bridge or tunnel. • Off the pavement or shoulder of the road. • Whenever a solid line marks the left side of your lane. • All of the above.