Malaria

What is malaria? Malaria is a life-

threatening disease caused by parasites of the genus Plasmodium, that are transmitted to people through the bites of infected mosquitoes.

Five species of the genus Plasmodium that cause nearly all malarial infections in humans: Falciparum Vivax Ovale Malariae Knowlesi

Malaria is spread by vectors (carriers). In malaria a mosquito serves as the vector that carries and transfers the infectious agent (Plasmodium), injecting it with a bite.

Transmitted exclusively though the bite of a Female Anopheline Mosquito

Epidemiology

3.3 billion people at risk worldwide

98% of Malarial deaths in Africa

Second leading cause of death from infectious diseases after HIV/AIDS in Africa

WHO estimates a child dies every 45 seconds from Malaria Makes up 20% all

childhood deaths 50 million women

become pregnant in Malaria endemic areas yearly Half in areas where P.

falciparum endemic

Hepatic schizont The actively dividing, multinucleated, parasite form in hepatocytes; produces no inflammatory response.

Trophozoite Metabolically active form of the malaria parasite living within the RBC; sometimes called the ring form.

P. vivax P. ovale

P. falciparum

Erythrocytic schizont: multinucleated stage in a RBC resulting from asexual multiplication of trophozoite. Each schizont contains a species determined number of meroziotes.

Merozoite: the name given to infective schizont components (see within the schizonts above) that break out of RBC or hepatocyte and then adhere to and penetrate a new RBC.

Gametocyte: morphologically distinctive sexual (male or female) form of the parasite which develops from some trophozoites in RBCs. It is infective to mosquito.

Sporozoite: the morphological form which develops in the mosquito salivary gland and is injected when the mosquito feeds, infecting humans.

P. vivax

P. falciparum

Incubation periodGenerally depends on the type of parasite:

P. falciparum - 9 to 14 days P. vivax - 12 to 18 days P. ovale - 12 to 18 days P. malariae - 18 to 40 days

However, incubation periods can vary from as short as 7 days, to several months for P. vivax and P. ovale

Life cycle Exoerythrocytic cycle:

(hepatic cycle) asexual reproduction within hepatocytes producing schizonts, which break out of the hepatocytes and invade other hepatocytes; occurs as a complete cycle only in P. vivax and P. ovale.

Intraerythrocytic cycle: (erythrocytic cycle) asexual reproduction within RBC's. Involves trophozoite to schizont, rupture of schizont, release of merozoites, invasion of new RBC, and production of new trophozoite.

The incubation period is both species and strain dependent:  e.g. P. falciparum 8-42 days; P. vivax 5 days to years

Only gametocytes infect mosquito

Only female Anopheles sp. mosquitos are vectors (no animal reservoir)      

Sporozoites

Liver

Asexual Reproduction

Single Sporozoite eventually 10,000 to >30,000 Daughter

Merozoites

Liver cell eventually bursts

Pathophysiology Only RBC trophozoites and schizonts cause disease

- no liver pathology caused by hepatic schizonts or sporozoites

- disease caused by: 

1. RBC destruction:  -  by parasite                                -  immune hemolysis                                - splenic pooling 2. Antigen-antibody complexes in kidney 3. Schizonts of P. falciparum sticking to post-capillary venules (esp. cerebral) endothelial cells4. Cytokines and other ill-defined shock, proinflammatory and capillary leakage producing products

Clinical Manifestations First symptoms of malaria are nonspecific Lack of a sense of well-being Headache Fatigue Abdominal discomfort Muscle aches

followed by Fever similar to the symptoms of a minor viral illness

Shortly accompanied by Headache Chest pain Abdominal pain Arthralgia (joint pain) Myalgia (muscle pain) Diarrhea Nausea Vomiting Orthostatic hypertension

Classic paroxysms Fever spikes Chills and rigors

occur at regular intervals, are relatively unusual and suggest infection with P. vivax or P. ovale

Childhood febrile convulsions Generalized seizures (associated with p. falciparum)

Physical findings Fever Malaise Mild Anemia Mild jaundice Palpable Spleen (in some cases)

Severe Malaria

Pathogenesis Clinical features

Cerebral Sluggish flow caused by sticky knobs on parasitized red cells leading to stagnant hypoxia and vascular damage.

Impaired level of consciousness. Hyperpyrexia. Convulsions. Generalized and localized neurological signs.

Anemia Destruction of parasitized and nonparasitized red cells by immune complexes, bone marrow suppression and splenic pooling.

Pallor and jaundice. High output cardiac state.

Renal Acute tubular necrosis resulting from sluggish blood flow and hypotension. Hemoglobinuria.

Oliguria. Haemoglobinuria. Acute renal failure.

Gastro-intestinal

Unknown Diarrhea.

Pathogenesis Clinical features

Respiratory Increased pulmonary capillary permeability.

Cough. Crepitations, pulmonary edema, iatrogenic fluid overload, bronchopneumonia.

Hepatic Unknown. ? Partially due to haemodynamic changes.

Jaundice (mainly attributable to haemolysis). Elevated serum enzyme levels, impaired elimination of drugs, prolonged prothrombin time, bleeding.

Fluid & electrolyte balance

Unknown. ? Partially due to inappropriate release of antidiuretic hormone.

Increased intravascular volume. Electrolyte changes, hypoglycemia, hyperkalemia and hemolysis.

Obstetric Sluggish blood flow in placental vessels leading to vascular damage.

Fetal death. Premature labour.

DiagnosisExamination of both thick & thin smears: Use shape and size of:   trophozoite, schizont and

gametocyte Percentage of RBCs with parasites (very rarely

over >1% parasitemia in P. vivax, ovale or malariae)

Metabolic debris in RBC around parasite (called Schuffner's dots in P. vivax infection)

Size of RBCs which contain parasites (P. vivax and ovale infect younger (larger) RBCs)

RDTs or Dipstick/Malaria Rapid Diagnostic Devices (MRDD) PCR (no-go)

Rapid, simple, sensitive, and specific antibody-based diagnostic stick or card tests that detect P. falciparum–specific, in finger-prick blood samples

RDTs are replacing microscopy in many areas because of their simplicity and speed, but they are relatively expensive and do not quantify parasitemia

Antibody and PCR tests have NO role in the diagnosis of malaria except that PCR is increasingly used for genotyping and speciation in mixed infections

There may be a persistent gametocytemia

Phagocytosed malarial pigment is sometimes seen inside peripheral-blood

Normochromic, normocytic anemia is usual

WBC count is generally normal (may be raised in severe infections)

Monocytosis, lymphopenia, eosinopenia, lymphocytosis and eosinophilia (after the acute infection)

ESR, CRP are high Trombocytopenia may

occur

Complications Acute Renal Failure Acute Pulmonary Edema (ARDS)

Hypoglycemia Spontaneous Bleeding Convulsions Aspiration pneumonia Bacterial Sepsis

Who is at risk? Young children Non-immune pregnant women Semi-immune pregnant women Semi-immune HIV-infected pregnant women People with HIV/AIDS International travellers from non-endemic areas Visiting immigrants from endemic areas and their

children

Treatment According to WHO, in areas where Malaria is common

treatment should start as soon as signs and symptoms appear, ideally within 24 hours.

People with uncomplicated malaria can be treated as outpatients, while those with severe malaria need to be hospitalized.

In non-endemic areas WHO recommends that patients with uncomplicated or severe malaria should be kept under clinical observation if possible.

Patients with P. falciparum infection and severe symptoms who cannot take their medications orally should receive them intravenously.

The best available treatment, particularly for P. falciparum malaria, is artemisinin-based combination therapy (ACT)

Clinical cure - eradication of RBC trophoziotes and schizonts 

Radical cure - eradication of RBC trophozoites and schizonts and hepatic schizonts (primaquine for 14 days, chloroquine for pregnant women)

Different drugs required for different stages of life cycle (eg. primaquine and Malarone for hepatic schizonts and gametocytes) (mefloquine, quinine and chloroquine for RBC schizonts and trophozoites)

Drug resistance Resistance to antimalarial medicines is a recurring problem. Resistance of P. falciparum to previous generations of medicines, such as chloroquine and sulfadoxine-pyrimethamine (SP), became widespread in the 1970s and 1980s. Instead nowadays WHO recommends ACT.

Malaria Control Framework

Prevention No safe, effective, long lasting vaccine

available Avoidance of exposure to mosquitoes (dusk

and dawn) Insect repellents containing 10–35% DEET (or

7% Picaridin) Suitable Clothing Insecticide-impregnated bed nets or other

materials