for students
Dr.T.V.Rao MD

Malaria – Early History

The symptoms of malaria were described in ancient Chinese medical writings. In 2700 BC, several characteristic symptoms of what would later be named malaria were described in the Nei Ching,

Hippocrates and Malaria

Hippocrates, a physician born in ancient Greece, today regarded as the "Father of Medicine", was the first to describe the manifestations of the disease, and relate them to the time of year and to where the patients

 Name

is derived from Italian

Mal’ aria or bad air
Malaria continues to be most important cause of fever and morbidity in the Tropical world Malaria has been eradicated from Europe, Most of North America, USA South America Korea and Japan,

Malaria-endemic Areas 2000

Why it is important in Medicine
 Malaria

remains the world's most devastating human parasitic infection. Malaria affects over 40% of the world's population. WHO, estimates that there are 350 - 500 million cases of malaria worldwide, of which 270 - 400 million are Falciparum malaria, the most severe form of the disease.

Malaria Kills more people than AIDS
 Malaria

kills in one year what AIDS kills in 15 years. For every death due to HIV/AIDS there are about 50 deaths due to malaria. To add to the problem is the increasing drug resistance to the established drug.

History – Events on Malaria
   

1880 - Charles Louis Alphose Lavern discovered malarial parasite in wet mount 1883 - Methylene blue stain - Marchafava 1891 - Polychrome stain- Romanowsky 1898 - Roland Ross - Life cycle of parasite transmission, wins Nobel Prize in 1902 1948 - Site of Exoerythrocytic development in Liver by Shortt and Garnham

Major Developments in 20th Century
 1955

- WHO starts world wide malaria eradication programme using DDT  1970 – Mosquitos develop resistance to DDT Programme fails  1976 – Trager and Jensen in vitro cultivation of parasite

Charles Louis Alphonse Laveran,

Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine, Algeria, was the first to notice parasites in the blood of a patient suffering from malaria. This occurred on the 6th of November 1880. For his discovery, Laveran was awarded the Nobel Prize in 1907.
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Ronald Ross

In August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes For his discovery, Ross was awarded the Nobel Prize in 1902.
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Nobel Prizes in Malaria

The discovery of this parasite in mosquitoes earned the British scientist Ronald Ross the Nobel Prize in Physiology or Medicine in 1902. In 1907, Alphonse Lavern received the Nobel prize for his findings that the parasite was present in human blood.

Chloroquine (Resochin) (1934, 1946)

Chloroquine was discovered by a German, Hans Andersag, in 1934 at Bayer I.G. Farbenindustrie A.G. laboratories in Eberfeld, Germany. He named his compound resochin. Through a series of lapses and confusion brought about during the war, chloroquine was finally recognized and established as an effective and safe antimalarial in 1946 by British and U.S.
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Malaria a vector borne Disease

Malaria is a vector-borne infectious disease caused by protozoan parasites. It is widespread in tropicl and subtropical regions, including parts of the Americas, Asia, and

Female Anopheles Mosquitos transmit Malaria

Parasites Cause of Malaria
is caused by an infection by one of four single celled Plasmodia species, they are: falciparum, vivax, malariae, and ovale. The
 Malaria

most dangerous of the four is.P.falciparum

Newer species

A fifth species, Plasmodium knowlesi, causes malaria in macaques but can also infect humans.

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SPOROZOA belong to phylum Apicomplexa – contains two classes 1 Haematozoea 2 Coccidea Belong to class Haematozoea occur in the blood of the vertebrate hosts contain two orders Haemosporidia (genus Plasmodium – Malaria ) Piroplasmidia (containing genus Babesia)

Structure of Malarial parasite

Falciparum most Dangerous
 Falciparum

accounts for 90% of deaths due to malaria and vivax is the most widely spread species because it exists in both temperate and tropical climates (Encarta). The malaria life cycle is a complex system with both sexual and asexual aspects .
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A complex Life cycle

Human Cycle
1 Pre erythrocytic schizogony 2 Erythrocytic Schizogony 3 Gametogony 4 Exoerythrocytic schizogony
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Events in Humans start with Bite of Mosquito
Man – Intermediate host.  Mosquito – Definitive host – Sporozoites are infective forms  Present in the salivary gland of female anopheles mosquito  After bite of infected mosquito sporozoites are introduced into blood circulation.

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Period of Pre erythrocytic cycle

P.vivax 8 days  2 P.falciparum – 6 days  3 P.malariae - 13 – 16 days,  4 P.ovale 9 days On maturation Liver cells ruputure Liberate Merozoites into blood stream
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Pre erythrocytic cycle

Sprozoites undergo developemtnal phase in the liver cell Sprozoites are elongated and spindle shaped become rounded inside the liver parenchyma Multiple nuclear divisions develop to Schozonts A Schizont contains 20,000 – 50,000 merozoites.
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Malaria Life Cycle Life Cycle

Oocyst Sporozoites Mosquito Salivary Gland



Exoerythrocytic (hepatic) cycle

Hypnozoites (for P. vivax and P. ovale)

Erythrocytic Cycle


Exo-erythrocytic (tissue) phase
 P.

malariae or P. falciparum sporozoites do not form hypnotizes, develop directly into pre-erythrocytic schizonts in the liver  Pre-erythrocytic schizogeny takes 6-16 days post infection  Schizonts rupture, releasing merozoites which invade red blood cells (RBC) in liver

Affinity of Parasite to Erythrocytes
  

P.vivax P.malariae P.ovale

Infectes only young or Old Erythocytes

 P.falciparum


Infects all age

Also adhere to the endothelial lining of Blood vessesl Causes the obstruction, Thrombosis and Local Ischemias

Erythrocyte cycle
 Merozoites

released invade red cells  P.vivax infects young erythrocytes  P.malariae Infects old erythrocytes  P.falciparum infects RBC of all ages  The Merozoites are pear shaped 1-5 microns in length  The receptors for Merozoites are on red cells in the glycoprotein

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Erythrocytic Schizogony

Liberated Merozoites penetrate RBC Three stages occur 1 Trophozoites 2 Schizont 3 Merozoite

Erythrocytic cycle

  

Ruptured red cells release Merozoites which attack new red cells Continue with Schizogony Repeated cycles will continue In P.falciparum infected erythrocytes with Schizonts aggregate in the capillaries of brain and other internal organs Only ring forms are seen in the blood smears


After invasion grow and feed on hemoglobin Blue cytoplasm and red nucleus, Called as Signet ring appearance Hence called ring form

 When

the Trophozoite is fully developed becomes compact.  Malarial pigments are scattered through the cytoplasm  The Nucleus is large and lies at the periphery starts dividing.  Becomes Schizont

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Plasmodium vivax
        

Number of merozoites 12 to 24 arranged in grape like clusters RBC enlarged Schuffner’s dots present Yellowish brown fine granules Schizont 9-10 microns fills and enlarged Red cell Gametocytes – spherical or globular Size much larger than red cell Male 9 microns Female 10 – 11 microns
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 

RBC is normal size Maurer’s dots 9 large red spots sometimes basophilic stippling Dark brown or blackish one or two solid blocks Gametocytes Crescentric, larger than a red cell 9 -10 microns, male and female 12- 14 microns

Plasmodium falciparum

Plasmodium malaria
   

 

RBC Normal size Contain Ziemann’s stippling Contain dark brown coarse granules Schizont – 6 – 7 microns almost fills a normal sized red cell. Gametocytes Spherical or globular Size much larger than a red cell

Plasmodium ovale
    

Infected RBC slightly larger Contain Schuffner’s dots coarse granules Schizont 6.2 microns fills three quarters Merozoites 6 -12 fills three quarters Gametocytes Spherical or globular, much larger than a red cell
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Exo-erythrocytic (tissue) phase
 P.

malariae or P. falciparum sporozoites do not form hypnozites, develop directly into pre-erythrocytic schizonts in the liver  Pre-erythrocytic schizogeny takes 6-16 days post infection  Schizonts rupture, releasing merozoites which invade red blood cells (RBC) in liver

Exo Erythrocytic Schizogony
 Some

Sprozoites do not undergo sporogony in the first instance  But go into resting stage called as Hypnozoites,( hibernation )  Within 2 years reactivate to form Schizonts release Merozoites and attack red cell and produce relapses  Absent in P falciparum

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      

Merozoites differentiate into Male and female gametocytes Macrogametocytes also called female gametocytes Microgametocyte also called as male gametocytes They develop in the red cells Found in the peripheral blood smears Microgametocyte of all species are similar in size Macro gametocytes are larger in size.

Mosquito cycle A definitive Host – Mosquito

Mosquito cycle Sexual cycle
   

Sexual cycle will be initiated in the Humans by the formation of Gametocytes Develop further in the female Anopheles


Only mature sexual forms are capable of further development in Mosquito In midgut one Microgametocyte develops into 4-8 thread like filamentous structures named Micro gametes From one macrogametocyte only one macrogamete is formed

Events in Mosquitos
 Fertilization

occurs when a Microgametocyte penetrate into Macrogametocyte  Fertilized macrogametocyte is known as ZYGOTE  ZYGOTE matures into OOKINETE  OOKINETE to OOCYST

Formation of Sporozoites in Mosquitos.

 

OOCYST matures with large number of Sporozoites ( A few hundred to thousands.) OOCYST ruptures and release SPOROZOITES in the body cavity of Mosquito There is a specific predilection for salivary glands Now capable to transmit the infection to new Host
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Pathology and Pathogenesis
 Sporozoites

result from sexaul and sporogenic cycle of development in mosquitoes and injected into human blood serum.  Events start with bite of Infected Anopheles Mosquitoes  Sporoozoites enter liver, in 1 hour infect the parenchymal cell.

Pathology and Pathogenesis
 Sporozoites

result from sexaul and sporogenic cycle of development in mosquitoes and injected into human blood serum.  Events start with bite of Infected Anopheles Mosquitoes  Sporoozoites enter liver, in 1 hour infect the parenchymal cell.

Pathogenesis in Pre Erythrocyte cycle
   

Numerous asexual progeny – Merozoites ruputure and leave from liver cells Enter the Blood and invade Erythrocytes Erythrocytic cycle starts – Multiply in species specific fashion Broods of Merozoites appearing at 48 hour interval in P.ovale, P.vivax , P.falciparum P.malariae appear in 72 hour cycles,

Chooses to enter the RBC
   

Specific for each species They pit on red cells By endocytosis enters the RBC Becomes a Trophozoites

 When

the Trophozoite is fully developed becomes compact.  Malarial pigments are scattered through the cytoplasm  The Nucleus is large and lies at the periphery starts dividing.  Becomes Schizont

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Cycles differs in Different species
Cycle repeats every 48 hours in 1 P.falciparum 2 P.ovale 3 P.vivax Repeats every 72 hours In P.malariae
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Incubation period varies according to species
 Which

includes Exo eythrocytic cycle time and one or two erythocytic cycles,  P.vivax and P.falciparum 10 – 15 days (can vary from weeks to months)  P.malariae infection can start after 28 days.
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Clinical Features of Malaria

Clinical Manifestations are related to cycle of events in relation to RBC

How Malaria present Clinically
Stage 1  Chills for 15 mt to 1 hour  Caused due to rupture from the host red cells escape into Blood  Preset with nausea, vomitting,headache

– Stage 2
 Fever

may reach upto 400c may last for several hours starts invading newer red cells.

Clinical Malaria
 Stage

3 Patent starts sweating, concludes the episode Cycles are frequently Asynchronous Paroxysms occur every 48 – 72 hours In P.malariae pyrexia may lost for 8 hours or more and temperature my exceed 410c

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More commonly, the patient presents with a combination of the following symptoms
      

Fever Chills Sweats Headaches Nausea and vomiting Body aches General malaise.
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Early symptoms
 The

common first symptoms – fever, headache, chills and vomiting – usually appear 10 to 15 days after a person is infected. If not treated promptly with effective medicines, malaria can cause severe illness and is often fatal.

What are the characteristics of a malaria attack

 

Fever and shivering. The attack begins with fever, with the temperature rising as high as 40ºC and falling again over a period of several hours. A poor general condition, feeling unwell and having headaches like influenza. Diarrhea, nausea and vomiting often occur as well.
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Malaria the disease

9-14 day incubation period Fever, chills, headache, back and joint pain Gastrointestin al symptoms (nausea, vomiting, etc.)

Clinical events
 The

symptoms often associated with malaria are due to bursting red blood cells and clogged capillaries of major organs. Infection occurs when an infected anopheles mosquito feeds on an individual releasing sporozites into the blood stream. Mosquitos can carry more than one species and thus can infect peoples with more than one species
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Malaria stages of the disease

Malaria intensifies
  

 

Symptoms intensify Irregular high fever Anxiety, delirium and other mental problems Sweating, increased pulse rate, severe exhaustion Worsening GI symptoms Enlarged spleen and liver

Broad clinical manifestations of Malaria
 Fever  Sweating  Anemia  Splenomagaly  Irratability  Coma,

(enlarged spleen)

Retinal Hemorrages   Algid Malaria ( a shocklike syndrome)  Respiratory distress syndrome

Periodicity can be clue in Diagnosis and species relation

Malaria tertiana: 48h between fevers (P. vivax and ovale) Malaria quartana: 72h between fevers (P. malariae) Malaria tropica: irregular high

Malaria the disease

Pathogenesis of Malaria

In highly endemic areas: high mortality among children due to severe anemia, children who survive beyond the first years show decreasing parasitemia and disease (this immunity is not sterile and depends on constant exposure)
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Cytokines & toxins
„ Malaria produces a strong Th-1 type response „ Elevated serum levels of IFN γ and TNFα „ Cytokines can induce (mimic) many of the symptoms and signs of malaria (shivering, headache, chills, spiking fever, sweating, vasodilation, hypoglycemia)

Hatched=chill Black=rigor Clear=sweating

Cerebral Malaria
Malignant malaria can affect the brain and the rest of the central nervous system. It is characterized by changes in the level of consciousness, convulsions and paralysis.

Cerebral Malaria
   

Present with Hyperpyrexia Can lead to Coma Paralysis and other complications. Brain appears congested

Pathogenesis of Cerebral malaria

„ High cytokine levels could be toxic on their own „ High levels of cytokine also enhance the second process thought to be responsible for cerebral malaria: sequestration of infected RBCs

Sequestration & cytoadherence

Rosetting (adhesion of infected RBCs to other RBCs) and clumping (adhesion between infected cells) was first observed in in vitro culture Rosetting was also found in 50% of field isolates and correlated strongly with the severity of the observed disease

Sequestration & cytoadherence
How do parasite proteins travel to the surface of the RBC?  This is a considerable challenge as RBC lack functional secretory apparatus  Why do patients fail to mount an effective immune response against antigens that are presented this prominently?

Black Water Fever
 In

malignant malaria a large number of the red blood corpuscles are destroyed. Haemoglobin from the blood corpuscles is excreted in the urine, which therefore is dark and almost the colour of

How long Malaria infection can lost in Man
 

 

Without treatment P.falciparum will terminate in less than 1 year. But in P.vivax and P.ovale persist as hypnozoites after the parasites have disppeared from blood. Can prodce periodic relapses upto 5 years In P.malariae may last for 40 years ( Called as recrudescence X relapse ) Parasites survive in erythrocytes Liver ?

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Why Falciparum Infections are Dangerous
 Can

produce fatal complications, 1.Cerebral malaria 2.Malarial hyperpyrexia 3.Gastrointestinal disorders. 4.Algid malaria 5 Black water fever can lead to death

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Complication of P.malariae

Can produce Nephrotic syndrome Affects mainly children of years age

Pernicious Malaria Carries a High Mortality

  

On few occasions life threading complications can occur. Occurs in infections with P.falciparum Associated with Heavy parasitaztion Grouped into three types 1. Cerebral Malaria 2 Algid malaria 3 Black water fever

Uncomplicated Malaria
 The

classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:  a cold stage (sensation of cold, shivering)  a hot stage (fever, headaches, vomiting; seizures in young children)  and finally a sweating stage (sweats, return to normal temperature, tiredness)

Malaria A Major Health problem of Tropical countreis

Pernicious Malaria
  

Is a life threatening complication in acute falciparum malaria It is due to heavy parasitization Manifest with 1 Cerebral malaria – it presents with hyperpyrexia, coma and paralysis. Brain is congested 2 Algid malaria – presents with clammy skin leading to peripheral circulatory failure.

Complication in Malaria
 Pulmonary

edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment  Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets)  Cardiovascular collapse and shock

Black water Fever

  

It is a manifestation of infection with P.falciparum occuring in persons who have been previously infected and have had been inadequate dose of quinine It is characterized by intravascular hemolysis fever, and Haemoglobunuria Cardiovascular collapse and shock Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets)

Other Complications In Malaria
 Acute

kidney failure  Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites  Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia

 Influenced


– – – – – – –

Genetics Age Health condition Pregnancy status Intensity of transmission in region Length of exposure Maintenance of exposure


– Red cell polymorphisms associated with some protection
    Hemoglobin S sickle cell trait or disease Hemoglobin C and hemoglobin E Thalessemia – α and β Glucose – 6 – phosphate dehydrogenase deficiency (G6PD)

– Red cell membrane changes
 Absence of certain Duffy coat antigens improves resistance to P.v.


– Transferred from mother to child
 3-6 months protection  Then children have increased susceptibility

– Increased susceptibility during early childhood
 Hyper- and holoendemic areas
– By age 5 attacks usually < frequent and severe – Can have > parasite densities with fewer symptoms

 Meso- or hypoendemic areas
– Less transmission and repeated attacks – May acquire partial immunity and be at higher risk for symptomatic disease as adults


– No complete immunity
 Can be parasitemic without clinical disease

– Need long period of exposure for induction – May need continued exposure for maintenance – Immunity can be unstable
 Can wane as one spends time outside endemic area  Can change with movement to area with different endemicity  Decreases during pregnancy, risk improves with increasing gravidity

Laboratory Diagnosis of Malaria

Diagnostic Tools for Human Infections with Malaria
 Blood

film examination  Serology - IFA  PCR

Blood collected with sterile technique

Making the smears

Making of Thick smear

Thin and Thick smear

Appearance of Thick and Thin Smears

 Malaria

parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria
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How parasites appear

QBC system has evolved as rapid and precise method in Diagnosis

The QBC Malaria method is the simplest and most sensitive method for diagnosing the following diseases.
– – – Malaria Babesiosis Trypanosomiasis (Chagas disease, Sleeping Sickness) – Filariasis (Elephantiasis, Loa-Loa) – Relapsing Fever (Borreliosis)
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QBC system

Appearance of Malarial parasite in QBC system

Antigen Detection Methods are Rapid and Precise
 

Antigen Detection Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings


Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience.
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Newer Diagnostic methods
Molecular Diagnosis
 Parasite

nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).

Types of Serological Assays Malaria
Antibody Detection
Indirect Fluorescent Antibody Enzyme immunoassays

Antigen Detection

Antibody Detection
Antigen Patient’s serum contains specific and non-specific antibodies =

Antigen-antibody complex

Antibody Detection
+ =

Antigenantibody complex

*-labeled antibody to
human antibody

Antigen-antibodyantibody complex


Indirect Fluorescent Antibody (IFA)

Microscope slide

Enzyme Immunoassay (EIA/ELISA)
enzyme substrate




Antigen Detection

Monoclonal antibody

Antigen in patient’s serum

Antigen-antibody complex

Antigen Detection

Antigen-antibody complex

Immobiliz ed monoclon al antibody

Antibody-antigenantibody complex

Antigen Detection Malaria

Immunochromatographic Dipstick
Optimal Assay

P. falciparum specific monoclonal antibody
Plasmodium pan specific monoclonal antibody


Malaria IFA Test
Sensitivity = 98% Specificity = 99.5%

Sulzer et al, Am J Trop Med Hyg 1969;18:199-205 Sulzer et al, Bull Wld Hlth Org 1971;45:375-379

P malaria

Malaria IFA Test Initial detection of antibodies
 Parasitemia precedes antibody  P. vivax

2-6 days

– P. falciparum and P. malariae 4-6 days
 If parasitemia is suppressed by

treatment, may develop detectable antibody

Determination of Infecting Species
Non-Immune  Samples drawn 0-14 days post onset: Highest titer was to the infecting species in 81%  Samples drawn 15-60 days post onset: Highest titer was to the infecting species in 96%

Malaria IFA Test

Determination of Infecting Species
 Is possible in non-immune

Malaria IFA Test

individuals with primary infection.  Is NOT possible in immune individuals because their antibody response reflects multiple infections with multiple species.

Malaria IFA Test
Antibody Persistence after Treatment Non-Immunes (Vietnam Vets with Pv) 53% IFA negative at 6 mo. post-Rx  59% IFA negative at 12 mo. post-Rx

Wilson et al, Am J Trop Med Hyg 1970;19:401-404

Malaria IFA Test
Antibody Persistence after Treatment Non-Immunes (Vietnam Vets with Pv) 53% IFA negative at 6 mo. post-Rx  59% IFA negative at 12 mo. post-Rx

Wilson et al, Am J Trop Med Hyg 1970;19:401-404

Sensitivity of Tools for Diagnosis of Malarial Infection
Most sensitive: Antibody detection 2. PCR 3. Blood film examination

Diagnosis of Untreated Acute Malaria
 Blood film

examination  PCR

Diagnosis of Chronic Malaria
 Screen with serology

If IFA positive:  May do blood film examination  May do PCR

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Diagnosis of Treated Recent Malaria
 Serology  Blood film

examination  PCR

Malaria Relapses

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.


Over view of Treatment options in Malaria
       

Most drugs used in treatment are active against the parasite forms in the blood (the form that causes disease) and include: Chloroquine Sulfadoxine-pyrimethamine (Fansidar®) Mefloquine (Lariam®) Atovaquone-proguanil (Malarone®) Quinine Doxycycline Artemisin derivatives (not licensed for use in the United States, but often found overseas)

 In

endemic areas, the World Health Organization recommends that treatment be started within 24 hours after the first symptoms appear. Treatment of patients with uncomplicated malaria can be conducted on an ambulatory basis (without hospitalization) but patients with severe malaria should be hospitalized if possible.
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What is presumptive treatment?
 

Presumption - In an area with high transmission of malaria, it should be presumed that ALL cases of fever are due to malaria. Treatment - First loading dose of Chloroquine should be administered immediately after collecting the blood specimen, even without waiting for its report. If the fever is indeed malaria, this treatment alleviates symptoms early, may be well before the test result is available. If it is malaria, Chloroquine also prevents the spread of malaria by destroying the gametocytes of P. vivax (the more common malaria). If it is not malaria, nothing is lost, for Chloroquine at this dose is safe and has no adverse effects!

Radical treatment

Radical treatment is administration of Primaquin to all confirmed cases of malaria. In P. vivax malaria, 2 weeks' therapy with Primaquin completely cures the infection in the host by its tissue schizonticidal activity and thereby prevents relapses. In P. falciparum malaria, a single dose of primaquine destroys the gametocytes, thereby prevents the spread of the infection into the mosquito.

Use of Primaquin
Primaquine is active against the dormant parasite liver forms ( hypnozoites) and prevents relapses. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency.
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Drug Resistance

Choroquine Resistance
 Chloroquine

resistant P. falciparum (CRPF) first developed independently in 3 to 4 foci in Southeast Asia, Oceania , and South America in the late 1950's and early 1960's. Since then, Chloroquine resistance has spread to nearly all areas of the world where falciparum malaria is transmitted

Chloroquine Resistance
 Chloroquine

resistant P. vivax (CRPV) malaria was first identified in 1989 among Australians living in or travelling to Papua New Guinea. CRPV has also now been identified in Southeast Asia, on the Indian subcontinent, and in South America. Vivax malaria, particularly from Oceania, also exhibits decreased susceptibility to primaquine.

Testing Drug Resistance

There are 4 basic methods for testing malaria for drug resistance: in vivo tests, in vitro tests, molecular characterization, and animal models. Of these, only the first 3 are routinely done In vivo tests: In these tests, patients with clinical malaria are given a treatment dose of an antimalarials drug under observation and are monitored over time for either failure to clear parasites or for reappearance of parasites.
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In vitro Testing
 In

vitro tests: In these tests, blood samples from malaria patients are obtained and the malaria parasites are exposed to different concentrations of antimalarials drugs in the laboratory. Some methods call for adaptation of parasites to culture first, while others put blood directly from patients into the test system.

Molecular Methods
 Molecular

characterization: For some drugs (Chloroquine, SP and similar drugs, atovaquone), molecular markers have been identified that confer resistance. Molecular techniques, such as polymerase chain reaction (PCR) or gene sequencing can identify these markers in blood taken from malariainfected patien

Resistance to Chloroquine - 1960

Resistance to Chloroquine 1970

Resistance to Chloroquine - 1980

Resistance to Chloroquine - 2000

Intensification of Chloroquine Resistance in Africa

Antimalarials Resistance 1998 (excluding CQ)

SP SP, Mefloquine Mefloquine SP, Mefloquine, Halofantrine, Quinine

Reports of Chloroquine Resistance in P.vivax

1995 1995 1995 1990 1991 1989

World Malaria Day, April 25

April 25 is World Malaria Day, which commemorates the date in 2000 when 44 African leaders committed to cutting malaria deaths in half by 2010. This year's World Malaria Day theme is "Counting Malaria Out." How does CDC contribute?

CDC's malaria Web site offers telediagnosis and treatment strategies

You can e-mail a digital image to the Centres for Disease Control and Prevention for telediagnosis, and if necessary download guidelines for treatment from its new malaria Web site,

Tele Net Working

Images of other suspected parasitic infections can be emailed to the CDC's Laboratory Identification of Parasites of Public Health Concern program ( ).

Doctortvrao’s ‘e’ learning series

Development of Vaccines
 Malaria

vaccines in development include: pre-erythrocytic or liverstage vaccines that aim to protect against the early stage of malaria infection; blood-stage vaccines that aim to reduce the severity of disease; and transmission-blocking vaccines that are intended to prevent mosquitoes that fed on an infected person from spreading

Future Ambitions

The malaria vaccine community aims to license—by 2015—a first-generation vaccine that has 50 percent efficacy against severe disease and death, with protection lasting at least one year without the need for boosting. They also aim to license—by 2025—a second-generation malaria vaccine that has a protective efficacy of at least 80 percent against clinical disease and with protection lasting for many years without a booster.

Why vaccines are Difficult
 

No licensed vaccine against malaria currently exists The parasite has evolved a series of strategies that allow it to confuse, hide, and misdirect the human immune system. The parasite changes through several life stages even while in the human host, presenting a different subset of molecules for the immune system to combat at each stage.

Simple protective Measures

There's no reason only poor people should get malaria': The moment Bill Gates released jar of mosquitoes at packed conference

Bill and Melinda Gates Foundation that announced last year it was donating £115 million to help develop a vaccine for the deadly disease.

Goal of Medical Humanity

Created for Medical and Paramedical students in Developing World
Dr.T.V.Rao MD Email

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