What does Malaria mean? The word “malaria” comes from the Italian mala aria, meaning “bad air.” When the term was coined, it was commonly believed that malaria was caused by breathing in bad air.
Overview Malaria is a mosquito-borne parasitic disease caused by genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions of the world. Around 400-900 million people are affected At least 2.7 million deaths annually. It is one of the major public health concerns
Epidemiology Around 300-500 million clinical cases of malaria are reported every year, of which more than a million die of severe and complicated cases of malaria. Malaria is known to kill one child every 30 sec, 3000 children per day under the age of 5 years. Malaria ranks third among the major infectious diseases in causing deaths after pneumococcal acute respiratory infections and tuberculosis, and accounts for approximately 2.6% of the total disease burden of the world.
Epidemiology (cont.) It mainly occurs throughout tropical regions 515 million clinical cases per year An estimated 655,000 people died from malaria in 2010 with two-thirds of these occurring in sub-Saharan Africa especially amongst children and pregnant women the incidence of malaria was greatly reduced between 1950 and 1960 but since 1970 there has been resurgence.
Who is at Risk? Most people who get malaria are travelers or people who live in an area with malaria transmission. Young children and pregnant women. Poor people that live in rural areas who lack knowledge, money and the access to health care.
Causative Agent Malaria is caused by species of Plasmodium. The genus Plasmodium contains over 200 species at least 11 species infect humans. Most important are: Plasmodium falciparum Plasmodium malariae Plasmodium ovale Plasmodium vivax Plasmodium knowlesi Plasmodium parasites are highly specific with female Anopheles mosquitoes
Vector Female mosquitos of genus Anopheles are primary hosts and transmission vectors. There are approximately 460 recognized species Over 100 can transmit human malaria Only 30–40 commonly transmit parasites of the genus Plasmodium Anopheles gambiae is one of the best known which transmits Plasmodium falciparum
Vector (cont.) Only female mosquitoes feed on blood while the males feed on plant nectar and do not transmit the disease.The females of Anopheles genus prefer to feed at nightThey start searching for a meal at dusk and continue throughout the night until they take a meal
Life Cycle & Pathogenesis Inside the vector (sexual reproduction): Young female mosquitoes ingest the malaria parasite by taking a blood meal from an infected human carrier The ingested gametocytes will differentiate into male and female gametes and then unite to form a zygote (ookinete) in the mosquito’s gut The resulting ookinete penetrates the gut lining to form an oocyst in the gut wall The oocyst ruptures to release sporozoites that migrate in the mosquito’s body to the salivary glands and are ready to infect new human hosts
Life Cycle & Pathogenesis Inside humans: Malaria develops via two phases: Exoerythrocytic: involves infection of liver Erythrocytic phase: involves infection of RBC (erythrocytes)
Life Cycle & Pathogenesis by taking a blood meal. A mosquito infects a person First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells, and escape back into the bloodstream. Then, the merozoites infect red blood cells, where they develop into ring forms, trophozoites and schizonts which in turn produce further merozoites. Sexual forms (gametocytes) are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.
Clinical Features P. falciparum (malignant tertian): It is the most dangerous of the malarias Onset is insidious, with malaise, headache and vomiting… commonly mistaken for influenza The fever has no particular pattern. Jaundice is common due to hemolysis & hepatic dysfunction There is hepatosplenomegaly Anemia develops rapidly
Clinical Features P. falciparum complications: Cerebral Malaria: the most grave complication, causing either confusion or coma without localizing signs. Convulsions Hypoglycemia Acute pulmonary edema Acure renal failure (Blackwater fever ) Metabolic acidosis Aspiration pneumonia Severe anemia Coagulopathy/Spontaneous bleeding
Causes of severe malaria P. falciparum-infected erythrocytes sequester in blood vessels, creating blockages. Infected erythrocytes also “stick to endothelium, platelets, and other erythrocytes” Rosetting -- cohesion of erythrocytes Leads to immune evasion because of lack of circulation through the spleen. Aids in the progression of the severity of malaria
Clinical Features P. vivax & P. ovale (benign tertian): In many cases the illness starts with several days of continued fever before the development of classical bouts of fever on alternate days. Fever starts with a rigor. The patient feels cold and the temperature rises to about 40 C. After an hour hot or flush phase begins. It lasts several hours and gives way to profuse perspiration and a gradual fall in temperature. The cycle is repeated 48 hours later. Anemia develops slowly
Clinical Features P. malariae infection (quartan): This is usually associated with mild symptoms and bouts of fever every third day. Parasitemia may persist for many years with the occasional recurrence of fever, or without producing any symptoms.
Hypnozoites It is the round or oval, uninucleate, dormant form of Plasmodium seen inside the liver cells during the intrahepatic (exoerythrocytic) stage of the parasite’s life cycle; it is believe to be the true latent stage associated with relapse in malaria. Hypnozoites are seen in: Plasmodium vivax Plasmodium ovale
Diagnosis Clinical Fever, sweat, chills, headache and muscle pain Serology PCR ELISA Blood Film (gold standard) Banana-shaped intraerythrocytic gametocytes identify P. falciparum Enlarged erythrocytes with Schuffner’s dots are characteristics of P. vivax Schuffner’s dots in ovale-shaped red blood cells are characteristic of P. ovale Band-form trophozoites are seen in P. malariae
BinaxNOW® Malaria Detects circulating malaria antigens in whole blood. 15 minute test The only FDA cleared rapid malaria test.
How the test works? The test targets the histidine-rich protein II (HRPII) antigen specific to P. falciparum and a pan-malarial antigen (aldolase), common to all four malaria species capable of infecting humans - P. falciparum, P. vivax, P. ovale, and P. malariae. It is intended to aid in the rapid diagnosis of human malaria infections and to aid in the differential diagnosis of Plasmodium falciparum infections from other less virulent malarial infections. Negative results must be confirmed by thin / thick smear microscopy.
Prevention Medications (will be mentioned in treatment) Vector control Mosquito nets and bedclothes Immunity (natural & vaccines) Education
Vector Control Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and southern Europe, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions. Malaria was eliminated from most parts of the USA in the early 20th century by use of the pesticide DDT.
Mosquito nets Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large "bed net" above the center of a bed such that it drapes down and covers the bed completely.
Immunity Natural immunity occurs, but only in response to repeated infection with multiple strains of malaria. A completely effective vaccine is not yet available for malaria, although several vaccines are under development. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. Other vaccine candidates, targeting the blood-stage of the parasites life cycle, have also been insufficient on their own. Several potential vaccines targeting the pre-erythrocytic stage are being developed.
Vaccines First proposed in 1960s, still nothing fully effectiveDifficulties include : Intracellular parasites Polymorphism and clonal variation Parasite induced immunosuppression Antigenic variation Evaluation and trials difficult to interpret High level of parasite mutation
Education symptoms of malaria Education in recognizing the has reduced the number of cases in some areas of the developing world by as much as 20%. Recognizing the disease in the early stages can also stop the disease from becoming a killer. Education can also inform people to cover over areas of stagnant, still water which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is most put in practice in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.
Treatment When properly treated, a patient with malaria can expect a complete recovery. The treatment of malaria depends on the severity of the disease; whether patients can take oral drugs or must be admitted depends on the assessment and the experience of the clinician. Uncomplicated malaria is treated with oral drugs. The most effective strategy for P. falciparum infection recommended by WHO is the use of artemisinins in combination with other antimalarials artemisinin- combination therapy, ACT, to avoid the development of drug resistance against artemisinin-based therapies.
Treatment Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine but artesunate has been shown to be superior to quinine in both children and adults. Treatment of severe malaria also involves supportive measures. Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.
ChemoprophylaxisAntimalarial tablets doseChloroquine resistance high Adult prophylactic RegimenMefloquine 250mg weekly Started 2-3 weeks before travel and continued until 4 weeks afteror Doxycycline 100mg daily Started 1 week before and continued until 4 weeks after travelOr Malarone 1 tablet daily From 1-2 days before travel until 1 week after returnChloroquine resistance absentChloroquine 300mg base weekly Started 1 week before &and proguanil 100-200mg daily continued until 4 weeks after travel