Malaria Dr. Mohammad sabri Introduction:

Malaria is a disease caused by one of four types of Plasmodium usually transmitted to humans by the bite of an infected female Anopheles mosquito that previously sucked the blood from a person with malaria. Malaria is one of the leading causes of disease and death in the world. It is estimated that there are 300-500 million new cases every year, with 1.5 to 2.7 million deaths worldwide. It occurs extensively in tropical and subtropical regions. Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever".The term malaria originates from Medieval Italian: mala aria — "bad air"; Etiologic Agent:- There are four species that commonly cause disease among humans: P. vivax, P. falciparum, P. ovale, and P. malariae. Mixed infections are possible. It is important to understand significant differences among the several species in terms of clinical illness, treatment, prophylaxis, and geographical distribution. Malaria due to P. falciparum causes the most severe symptoms and requires prompt intervention. Malaria parasites have a complex life cycle. After injection into the human host from anopheline mosquitoes, the parasites mature in the liver before being released into the bloodstream and invading red blood cells. The parasites multiply inside the red blood cells, eventually rupturing the cells, releasing more parasites into the bloodstream with accompanying high fevers. Some parasites differentiate into sexual forms (gametocytes) which, if ingested by another mosquito, can lead to the development of another generation of parasites, ready for transmission to another human host. The bloodstream cycle can persist for weeks to years, depending on the species involved. In malaria due to P. vivax and P. ovale, a dormant stage (hypnozoites) can persist indefinitely in the liver. Four species of Plasmodium can infect and be transmitted by humans.

. Malaria caused by Plasmodium falciparumSevere disease is largely caused by is generally Plasmodium malariaeand Plasmodium ovale, Plasmodium vivax

a milder disease that is rarely fatal.

pecies Appearance Periodicity Liver persistent

Plasmodium vivax

tertian yes

Plasmodium ovale

tertian yes

Plasmodium falciparum

tertian no

Plasmodium malariae

quartan no

Disease Severity and Duration

vivax ovale malariae falciparum

Initial Paraoxysm

Severity

moderate to

severe mild

moderate to

severe

Severe

Average

Parasitemia (mm3)

20,000 9,000 6,000

50,000-

500,000

Symptom Duration

(untreated)

3-8 weeks 2-3 weeks 3-24 weeks 2-3 weeks

Maximum

Infection Duration

(untreated)

5-8 years 12-20

months 20-50+ years 6-17 months

Anemia ++ + ++ ++++

Complications

renal cerebral

Life Cycle of Malaria:-

In nature, malaria parasites spread by infecting successively two types of hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites ("merozoites") that continue the cycle by invading other red cells. The blood stage parasites are those that cause the symptoms of malaria. When certain forms of blood stage parasites ("gametocytes") are picked up by a female Anopheles mosquito during a blood meal, they start another, different cycle of growth and multiplication in the mosquito. After 10-18 days, the parasites are found (as "sporozoites") in the mosquito's salivary glands. When the Anopheles mosquito takes a blood meal on another human, the sporozoites are injected with the mosquito's saliva and start another human infection when they parasitize the liver cells. Thus the mosquito carries the disease from one human to another (acting as a "vector"). Differently from the human host, the mosquito vector does not suffer from the presence of the parasite

During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites’ multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

Signs and symptoms:- The classic signs and symptoms of malaria are recurrent bouts of fever, chills, sweats, and headache. Other symptoms can occur, depending on the severity of infection, including gastrointestinal symptoms (vomiting, diarrhea), respiratory symptoms (cough, shortness of breath), muscle aches, etc. Fevers can recur at regular intervals (48 or 72 hours, depending on the malarial species) that coincide with a synchronized rupture of red blood cells. This periodicity may be masked. The severity of symptoms varies with the species of parasite involved, the stage of infection, the immunological history of the patient, and other factors. Persons in endemic areas may develop “concomitant” immunity—a relative resistance to symptoms that persists only with continued exposure, persistent low-level parasitemia, or frequent infections. P. falciparum infections are potentially life-threatening because the the proportion of red blood cells containing parasites can be greater than 10% which results in venous thrombosis or sludging in the capillaries. Complications of inadequately treated falciparum malaria include anemia, renal failure, shock, adult respiratory distress syndrome, encephalopathy, and acidosis. Disease caused by the other malarial species is rarely fatal, and can be quite mild. The classical presentation of malaria is: 1. The ‘cold stage’ associated with rigors (shaking). 2. The ‘hot stage’ where the patient becomes febrile, oftenexceeding 40oC associated with nausea and vomiting. 3. The ‘sweating’ stage where the temperature returns to normal The fever is referred to as a ‘swinging fever’ and the duration between fevers may point to a malaria. The Malarial Paroxysm

cold stage hot stage sweating stage

feeling of intense cold

vigorous shivering lasts 15-60 minutes

intense heat dry burning skin throbbing

headache lasts 2-6 hours

profuse sweating declining temperature exhausted and weak →

sleep lasts 2-4 hours

• P. ovale/P. vivax 38-42 hours between fevers (‘tertian fever’) • P. malariae 62-66 hours between fevers (‘quartan fever) . This clinical presentation is due to red blood cell rupture and subsequent merozoite release into the circulation. However in P. falciparum the timing of fevers tends to be less periodic. Other features include • headache • abdominal pain and on rare occasions may suggest an “acute abdomen”, • vomiting considered in the differential diagnosis. ** other Signs of malaria include: • conjunctival pallor (a sign of anaemia) • mild jaundice which is caused by haemolysis. P. falciparum may be associated with severe jaundice and is caused by liver damage • splenomegaly (the spleen is palpable). It takes only afew days for the spleen to enlarge in an acute attack of malaria. However, there are many causes of anaemia, jaundice and splenomegaly • hepatomegaly (liver enlargement). Other more general signs may include tachycardia (fast heart rate) with a bounding pulse, and tachypnoea (fast breathing rate) especially in children. Chronic malaria:- The persistence of malaria in the blood, especially in people who live in subtropical regions, leads to ‘chronicmalaria.’ Symptoms may include attacks of ‘ acute m alaria’ interspersed with anaemia, weight loss or other infections

Diagnosis:-

The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting ) are often not specific and are also found in other diseases (such as influenza and other common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness). In severe malaria (typically caused by P. falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria. Laboratory diagnosis :- *The mainstay of malaria diagnosis has been the microscopic examination of blood. used to make a diagnosis, Detection of malaria parasites in thick or thin peripheral blood films. Using Giemsa-stained, Only Ring forms and gametocytes can be found in blood film. *Detection of species specific parasite DNA in a sample of peripheral blood using a polymerase chain reaction test (PCR) . PCR (and other molecular methods) is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitemia in the field.

*For areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are commercial antigen detection tests that require only a drop of blood. Immunochromatographic tests (also called: Malaria Rapid Diagnostic Tests, Antigen-Capture Assay or "Dipsticks") have been developed, distributed and field tested. These tests use finger-stick or venous blood, the completed test takes a total of 15–20 minutes, and the results are read visually as the presence or absence of colored stripes on the dipstick, so they are suitable for use in the field.. One disadvantage is that dipstick tests are qualitative but not quantitative – they can determine if parasites are present in the blood, but not how many.

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 who can take oral drugs have to be admitted depends on the assessment and the experience of the clinician. Uncomplicated malaria is treated with oral drugs. 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. In general, chloroquine is the drug of choice for all Plasmodium except for chloroquine-resistant P. falciparum and chloroquine-resistant P. vivax. Primaquine, a drug that is active specifically against the liver stages, may be added for treatment of malaria due to P. vivax and P. ovale to prevent relapse but should not be used during pregnancy and can also cause complications in persons with G6PD deficiency. Treatment of P. falciparum is more complicated, because of widespread resistance to chloroquine, and, increasingly, mefloquine. Treatment is often with quinine plus a second drug, but it is essential to get up-to-date treatment recommendations particularly the appropriate recommendations for children, pregnant women, and persons with G6PD deficiency. Because of the potential for rapid clinical deterioration, clinicians should strongly consider hospitalizing patients with falciparum malaria, at least until the success of therapy is assured. For prophylaxis recommendations during travel.

Prevention and Control in Endemic Areas:- Prevention is an important component of malaria control in endemic countries. It is achieved through: •vector control •personal protection measures such as insecticide-treated bed nets •preventive treatment with antimalarial drugs of vulnerable groups such as pregnant women, who receive intermittent preventive treatment.

*Travelers from non-endemic countries should take precautions against acquiring malaria when they visit a malaria risk area.