DefinitionDefinition Malaria is a mosquito-borne

disease that causes over 2.7 million deaths per year according to estimates by the World Health Organization.

Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium

EtiologyEtiology•Malaria is caused by a parasite that is passed from one human to another by the bite of infected Anopheles mosquitoes. •After infection, the parasites (called sporozoites) travel through the bloodstream to the liver, where they mature and release another form, the merozoites. The parasites enter the bloodstream and infect red blood cells.

EtiologyEtiology•The parasites multiply inside the red blood cells, which then break open within 48 to 72 hours, infecting more red blood cells. The first symptoms usually occur 10 days to 4 weeks after infection, though they can appear as early as 8 days or as long as a year after infection. The symptoms occur in cycles of 48 to 72 hours.

EtiologyEtiologyMalaria can also be transmitted from a mother to her unborn baby (congenitally)and by blood transfusions. Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter.The disease is a major health problem in much of the tropics and subtropics. The CDC estimates that there are 300-500 million cases of malaria each year, and more than 1 million people die from it. It presents a major disease hazard for travelers to warm climates.In some areas of the world, mosquitoes that carry malaria have developed resistance to insecticides. In addition, the parasites have developed resistance to some antibiotics. These conditions have led to difficulty in controlling both the rate of infection and spread of this disease.

Exo-erythrocytic (hepatic) cycle

Sporozoites

Mosquito Salivary Gland

Malaria Life CycleLife Cycle

Gametocytes

Oocyst

Erythrocytic Cycle

Zygote

Schizogony

Sporogony

Hypnozoites(for P. vivax and P. ovale)

Clinical presentationClinical presentation

Early symptoms Headache Malaise Fatigue Nausea Muscular pains Slight diarrhea Slight fever, usually not intermittent

Could mistake for influenza or gastrointestinal infection

Clinical presentationClinical presentation

Acute febrile illness, may have periodic febrile paroxysms every 48 – 72 hours with

Afebrile asymptomatic intervals Tendency to recrudesce or relapse over

months to years Anemia, thrombocytopenia, jaundice,

hepatosplenomegaly, respiratory distress syndrome, renal dysfunction, hypoglycemia, mental status changes, tropical splenomegaly syndrome

Malaria Transmission Malaria Transmission CycleCycle

Parasite undergoes sexual reproduction in the mosquito

Some merozoites differentiate into male or female gametocyctes

Erythrocytic Cycle: Merozoites infect red blood cells to form schizonts

Dormant liver stages (hypnozoites) of P. vivax and P. ovale

Exo-erythrocytic (hepatic) Cycle: Sporozoites infect liver cells and develop into schizonts, which release merozoites into the blood

MOSQUITO HUMAN

Sporozoires injected into human host during blood meal

Parasites mature in mosquito midgut and migrate to salivary glands

Differential diagnosisDifferential diagnosis

At the onset of the disease it may be very difficult to differentiate malaria from viral fevers.

Jaundice and fever is also seen in viral hepatitis and other forms of hepatitis, cholecystitis and

hepatic abscess.

Dengue, Leptospirosis and hemolytic anemia have the common triad of pallor, icterus and

splenomegaly.

As the disease As the disease progressesprogresses

The patient becomes more drowsy and breathless suggesting ALI and ARDS.The

O2 concentration starts to drop and respiratory alkalosis sets in. Eventually he may be started on mechanical ventillation.

The kidneys start to fail and urine output lessens signifying acute renal failure.

Shock,hypoglycemia, lactic acidosis and DIC complete the picture of MOSF.

 The WHO publication, Drug resistance in malaria, describes the state of knowledge about this problem and outlines the current thinking regarding strategies to limit the advent, spread and intensification of drug-resistant malaria.

Resistance of Plasmodium falciparum to choloroquine, the cheapest and the most used drug is spreading in almost all the endemic countries.

Treatment of MalariaTreatment of Malaria

sulfadoxine-pyrimethamine

chloroquine

quinine

mefloquine

Artemisinin compounds

sulfadoxine-sulfadoxine-pyrimethaminepyrimethamine

These drugs act by sequential inhibition of enzymes of folate metabolism. Resistance to these drugs has developed over the past 30 years and is now wide spread. Resistance develops very rapidly and remains stable due to a single point mutation.

chloroquinechloroquine

Chloroquine acts by getting accumulated in the food vacuole where it inhibits heme polymerase. Resistant strains are able to efflux the drug by an active pump mechanism and release the drug at least 40 times faster than sensitive strains, thereby rendering the drug ineffective.

quininequinine

Resistance has brought this drug back to the limelight. Quinine remains quite effective even after extensive use.

mefloquinemefloquine

Resistance develops when the parasite is able to efflux the drug. Initially it was given at dose of 15mg/kg and was combined with sulfadoxine/pyrimethamine to reduce emergence of resistance.

Artemisinin compoundsArtemisinin compounds

These are peroxide antimalarials which release carbon centred free radicals when they come in contact with heme.

Objectives of monitoring antimalarial Objectives of monitoring antimalarial drug resistancedrug resistance

Evaluate the efficacy of first- and second-line drugs used in the treatment of malaria

Provide information for action

Tools for MonitoringTools for Monitoring

1.  Therapeutic efficacy tests

2. In vitro tests

3.  Molecular markers

Methods of ControlMethods of Control

Methods used to prevent the spread of disease, or to protect individuals in areas where malaria is endemic, includeprophylactic drugs, mosquito eradication, and the prevention of mosquito bites

The continued existence of malaria in an area requires a combination of high human population density, high mosquito population density, and high rates of transmission from humans to mosquitoes and from mosquitoes to humans.

Vector control

Prophylactic drugs

Indoor residual spraying

Mosquito nets and bedclothes

Vaccination

Vector controlVector control

It is done by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water.

Prophylactic drugsProphylactic drugs

Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Generally, these drugs are taken daily or weekly, at a lower dose than would be used for treatment of a person who had actually contracted the disease.

Indoor residual sprayingIndoor residual spraying

Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected areas.

Mosquito nets and Mosquito nets and bedclothesbedclothes

Mosquito nets help keep mosquitoes away from people, and thus greatly reduce the infection and transmission of malaria.

VaccinationVaccination

Vaccines for malaria are under development, with no completely effective vaccine yet available. Presently, there is a huge variety of vaccine candidates on the table.

Other testsOther tests

Generally the complete blood counts and platelets counts are of little benefit in the diagnosis but aid in assessing the severity and complications of the ongoing infection.

PfHRP2 dipstick or card test: monoclonal ab captures the parasite antigens. Only for

falciparum malaria.

LDH dipstick or card test

Drugs used to treat Drugs used to treat Malaria-First groupMalaria-First group

CHQ, Amiodaquine

Quinine, Quinidine

Mefloquine, Halofantrine

Lumefantrine

First group-adverse First group-adverse reactionsreactions

GI disturbances-nausea, vomiting, diarrhoea and

erosive or hemorrhagic gastritis with abdominal pain and hematemisis at times.

Cardiovascular instability- Prolonged QTc ventricular tachyarrythmia and hypotension

CNS-disorientation, abn behaviour, seizure

Metabolic- hypoglycemia

ALWAYS CHECK – K, MG, SUGAR before starting

Drugs used to treat Drugs used to treat malariamalaria

Doxy, Tetra – pregnancy, children, hepatic

Sulfadoxine-Pyrimethamine – sulfa allergy, renal failure

Artemisin derivatives - safe

Drugs used to treat Drugs used to treat Malaria-othersMalaria-others

Clindamycin

Azithromycin

Proguanil

Dapsone

Primaquine

Intravenous anti-Intravenous anti-malarial therapy- malarial therapy-

IndicationsIndicationsPresence of vomiting

Inability to start oral therapy may also be due to altered mental alertness and seizures.

Patients who are intubated and on ventillators.

Those who are critically ill.

Intra-venous therapyIntra-venous therapy

Chloroquine: intravenous 10 mg/kg max 600mg over 6-8 hrs followed by 15mg/kg max 900mg over next 24 hrs as slow infusion.

Quinine : intravenous 20mg/kg over 4 hrs; then 10mg/kg(max 600mg)three times a day.

Intra-venous therapy-Intra-venous therapy-severe f.malariasevere f.malaria

Artesunate 2.4mg/kg stat; followed by 2.4mg/kg at 12 hrs, 24hrs and then daily. OR

Artemether 3.2mg/kg stat im; then 1.6mg/kg od im.

PLUS

Add quinine 20mg salt/kg over 4 hrs; followed by 10mg/kg over 2-8 hrs slow infusion thrice a day.

PLUS

Doxy 100mg bd / tetra 250mg (4mg/kg) qds

Other supportive Other supportive therapytherapy

Maintain acid-base balance

Maintain blood sugar

Add folvite for hemolysis

Blood transfusions

Exchange transfusion

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