I am giving the old names for these malarias in parentheses to give some historical perspective in case you see these terms again. I will also explain how these old terms relate to the pathogenesis of these respective diseases and the associated fever patterns.
The life cycle of all species that infect humans is basically the same. There is an exogenous asexual phase in the mosquito called sporogony during which the parasite multiplies. There is also an endogenous asexual phase that takes place in the vertebrate or human host that is called schizogeny. This phase includes the parasite development that takes place in the red blood cell, called the erythrocytic cycle and the phase tthat takes place in the parencymal cells in the liver, called the exo-erythrocytic phase. The exo-erthrocytic phase is also called the tissue phase. The schizogeny that takes place here can occur without delay during the primary infection or can be delayed in the case of relapses of malaria. I will focus on the development of the parasite in the human host.
Definition 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
Etiology•Malaria is caused by a parasite that ispassed from one human to another bythe bite of infected Anophelesmosquitoes.•After infection, the parasites (calledsporozoites) travel through thebloodstream to the liver, where theymature and release another form, themerozoites. The parasites enter thebloodstream and infect red blood cells.
Etiology•The parasites multiply inside the redblood cells, which then break openwithin 48 to 72 hours, infecting more redblood cells. The first symptoms usuallyoccur 10 days to 4 weeks after infection,though they can appear as early as 8days or as long as a year after infection.The symptoms occur in cycles of 48 to72 hours.
EtiologyMalaria can also be transmitted from a mother to herunborn baby (congenitally)and by blood transfusions.Malaria can be carried by mosquitoes in temperateclimates, but the parasite disappears over the winter.Thedisease is a major health problem in much of the tropicsand subtropics. The CDC estimates that there are 300-500million cases of malaria each year, and more than 1 millionpeople die from it. It presents a major disease hazard fortravelers to warm climates.In some areas of the world,mosquitoes that carry malaria have developed resistance toinsecticides. In addition, the parasites have developedresistance to some antibiotics. These conditions have led todifficulty in controlling both the rate of infection andspread of this disease.
Malaria Life SporogonyCycle OocystLife Cycle Sporozoites Mosquito Salivary Zygote Gland Hypnozoites Exo- (for P. vivax and P. ovale) erythrocytic (hepatic) cycle Gametocytes Erythrocytic CycleSchizogony
Clinical presentation Early symptoms Headache Malaise Fatigue Nausea Muscular pains Slight diarrhea Slight fever, usually not intermittent Could mistake for influenza or gastrointestinal infection
Clinical 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 Cycle Exo-erythrocytic (hepatic) Cycle: Sporozoires injected Sporozoites infect liver cells and into human host during develop into schizonts, which release blood meal merozoites into the bloodParasitesmature inmosquitomidgut and Dormant liver stages MOSQUITO HUMANmigrate to (hypnozoites) of P.salivary vivax and P. ovaleglands Erythrocytic Cycle: Merozoites infect red blood cells to form Some merozoites schizonts Parasite undergoes sexual reproduction in differentiate into male or the mosquito female gametocyctes
Differential diagnosisAt 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 progressesThe 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 Malaria sulfadoxine-pyrimethamine chloroquine quinine mefloquine Artemisinin compounds
sulfadoxine-pyrimethamine 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.
chloroquine 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.
quinine Resistance has brought this drug back to the limelight. Quinine remains quite effective even after extensive use.
mefloquine 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 compounds These are peroxide antimalarials which release carbon centred free radicals when they come in contact with heme.
Objectives of monitoring antimalarial drug resistance Evaluate the efficacy of first- and second-line drugs used in the treatment of malaria Provide information for action
Tools for Monitoring1. Therapeutic efficacy tests2. In vitro tests3. Molecular markers
Methods 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 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 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 spraying Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected areas.
Mosquito nets and bedclothes Mosquito nets help keep mosquitoes away from people, and thus greatly reduce the infection and transmission of malaria.
Vaccination 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 testsGenerally 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 Malaria- First group CHQ, Amiodaquine Quinine, Quinidine Mefloquine, Halofantrine Lumefantrine
First group-adverse reactions GI disturbances-nausea, vomiting, diarrhoea anderosive 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 Malaria-others Clindamycin Azithromycin Proguanil Dapsone Primaquine
Intravenous anti-malarial therapy- Indications Presence of vomitingInability 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 therapyChloroquine: 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-severe f.malariaArtesunate 2.4mg/kg stat; followed by 2.4mg/kg at 12 hrs, 24hrs and then daily. ORArtemether 3.2mg/kg stat im; then 1.6mg/kg od im. PLUSAdd quinine 20mg salt/kg over 4 hrs; followed by 10mg/kg over 2-8 hrs slow infusion thrice a day. PLUSDoxy 100mg bd / tetra 250mg (4mg/kg) qds
Other supportive therapy Maintain acid-base balance Maintain blood sugar Add folvite for hemolysis Blood transfusions Exchange transfusion