Malaria: symtoms, treatment ,prevention and more

Malaria is a mosquito- borne parasitic protozoan disease that is caused by the genus plasmodium. Malaria is characterized by paroxysm of fever, chills, sweat, fatigue, anemia and splenomegaly. It has played a major role in human history and probably has caused more harm than any infectious disease known to man. Malaria is one of the Neglected Tropical Diseases (NTDs) and still contributes to huge number of deaths in the developing world especially among infants and young children.


There are five species that cause malaria in man and they include: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi.The main species causing severe and life threatening disease is falciparum and more than 98% of  falciparum malaria occur in Africa.

source:davidson’s principle and practice of medicine

Malaria can be transmitted by
· Bites from female anopheles mosquito
· Through blood transfusion
· Use of contaminated needle and
· From pregnant woman to a fetus inutero

female anopheles mosquito transmit malaria source CDC


Female anopheles mosquitoes carry sporozoites of plasmodium in their salivary glands, during a blood meal while the insect is feeding on the human blood through its proboscis, millions of sporozoites are introduced into the blood stream from the mosquitoes salivary gland, the infection in humans begin at this stage.

The microscopic and motile sporozoites rapidly get to the via the blood stream . In the liver they invade the hepatic parenchymal cells and go through a process of asexual reproduction , this is referred to as the intrahepatic or preerythrocytic schizogony or merogony stage.As a result of parasitic multiplication via an asexual process, one plasmodial sporozoite multiplies to produce between 10000 to over 30000 daughter merozoites.

The infested liver parenchymal cells become swollen and eventually burst releasing motile merozoites into the blood stream. Merozoites invade red blood cell and go through a multiplication process inside the red blood cells. The merozoites multiply up to six to twenty folds every 48 to 72 hours.

Humans begin to show symptoms of malaria when the parasitic density in the blood is about 50/litre of blood.

In Malaria infection caused by P. vivax and P. ovale , some of the parasites that get to the liver do not undergo the asexual reproduction immediately, instead they become dormant hypnozoites that remain in the liver parenchymal cells for three weeks to one year or longer before proceeding to reproduce. This dormant form is the reason for the characteristic relapse seen seen in P. vivax and P. ovale infections only.

From the blood stream merozoides invade red blood cells and become trophozoites. Attachment to red blood cells is achieved through specific receptors on the red blood cell membrane.

Specifically in P. vivax, the malaria parasite attaches to the Duffy blood-group antigen, Fya or Fyb .However most people from West Africa or with West African origin have the duffy negative FyFy phenotype and are hence resistant to P. vivax infection

During the early stages of the parasite residing in the red blood cell, the small ring forms of the four plasmodium species have a similar appearance under the light microscope, however as the trophozoites develop and enlarges, the parasite takes an irregular amoeboid shape, parasitic pigments develop and specie specific characteristics begin to surface.

The intraerythrocytic stage of plasmodium life cycle last for about 48hours except in P. malariae where it takes up to 72hrs. By the end of this stage the parasite would have grown well enough to occupy nearly most of the red bllod cell and consumed almost all the available hemoglobin.The parasite is here referred to as a schizont.the parasite again undergoes multiple nuclear divisions (schizogony or merogony) culminating in the rupture of the red blood cell ,each ruptured cell releases between 6 to 30 daughter merozoites that are capable of invading healthy red cells and repeating the cycle.

The manifestation of malaria in humans is caused by the direct effect of host immune responses as well as effects of red blood cell invasion and destruction.

Some of the parasites transform into morphologically distinct, sexual, gametocyte forms after a series of asexual cell divisions in p falciparum, however, gametocytes are formed earlier in P. vivax, P. ovale, P. malariae usually after release of parasites from the liver.These gametocytes are responsible for the continuous perpetration of the plasmodium species.

While the female anopheles mosquito enjoys a human blood meal during mosquito bite, female and male gametocyte are ingested by the mosquito. The male and female gametocyte reach the mosquito gut wall and fuse to form a zygote that matures into an ookinate. The ookinate developes, penetrates and encyst itself in the mosquito gut wall. This encyted ookinate hence bemoes an oocyst that continues multiple asexual cell divisions and eventually bursts to release numerous motile sporozoites. Through the hemolymph sporozoites get to the mosquito salivary gland where they await inoculation into human during the next human bite.

In the red blood cell
After invading the red blood cells, the parasite progressively degrades and destroys intracellular proteins especially hemoglobin. The potentially harmful heme produced is detoxified by polymerization to a biologically inactive form called hemozoin which is responsible for malaria pigment. The parasite also affects the red cell membrane properties by altering its transport properties,exposing cell surface cryptic antigens and inserting parasite derived proteins . Hence the red cells become more antigenic, less deformable with a more irregular shape.

About 12 – 15 hours after invasion of red blood cells occur in P. falciparum infections, the cell membrane bulges and bears a high molecular weight ,strain specific, plasmodium falciparum erythrocyte membrane adhesive protein (PfEMP1). These molecule is responsible for the attachment of the parasite to cell surface receptors on the endothelium of venules and capillaries, this is termed cytoadherance.

A number of vascular surface receptors have been implicated in the process of cytoadherance, the intercellular adhesion molecule 1 (ICAM-1) has been identified as the major adherant receptor in the brain, chondroitin sulfate B in the placenta and CD36 in most other tissues. Through the process of cytoadherance the infected erythrocytes stick inside tiny blood vessels and eventually block capillaries and venules.

Also at this stage in the pathogenesis, some red blood cells parasitised by p.falciparum attach themselves to uninfected red blood cells to form rosettes and and also to other parasitised cells (agglutination). The triad of cytoadherance,resetting and agglutination is unique to P. falciparum infection. These processes result in sequestration of parasitised red blood cells in vital organs especially the brain where they impair the microcirculation and cellular metabolism.

Parasites that are sequestered in vital organs continue to grow and proliferate and are able to escape the hosts’ defense mechanisms such as processing and filtration of blood in the spleen. Consequently the density of peripheral parasitaemia is not the true reflection of the total number of parasites in the body.

Their is also a reduction in the deformability of uninfected red blood cells in severe malaria such that their passage through the already partially obstructed capillaries and venules are compromised. All of these shortens the lifespan of red blood cells.

P. vivax and P. ovale show a marked predilection for young red blood cells, p.malarieae has predilection for old red blood cells.These three produce a level of peripheral parasiteamia that hardly exceepds 2% whereas p.falciparum invades red blood cells of different ages and can cause an infection with very high level of parasitaemia.

Host response
the host responds to malaria infection through non specific immunologic processes initially. The spleen cariies out an immunologic and filtrative clearance such that parasitised and healthy red blood cells are cleared from circulation.Red blood cells that escape the splenic clearance are eventually destroyed when the schizont ruptures. chemicals released as a result of scizont rupture activate macrophages and release of proinflamatory cytokines from mononuclear cells, circulating cytokines induce fever and mediate other pathologic processes.

While the non specific immunologic response stop the expansion of on going malaria infection, the susequent specific host immune response controls the infection.over time as a result of repeated infection of the host by strains of plasmodium, the host eventually becomes protected from malaria with high level parasitaemia but not from becoming infected.Due to this state of infection without illness, adults and older children in malaria residing in regions with intense and stable malaria transmission ( holoendemic and hyperendemic areas) often have asymptomatic parasitaemia as a result of protection conferred on them via humoral and cellular immunologic mechanisms that develops over the years.

Individuals that are immune to severe malaria have a polyclonal increase in the serum levels of igG,IgA and IgM antibodies though a large number of these antibodies are not related to the conferred immunity.

Antibodies are also produced against a wide range of antigenic parasitic proteins,in p falciparum,the high molecular weight variant protein erythrocyte membrane adhesive protein (PfEMP1) is the most significant.

passively tranferred igG antibodies from immune mothers to young infants in utero gives a relative protection from severe forms of malaria in the first few months of life.However this immunity wanes over time when a person lives the endemic zone for a long period of time


Over a hundred countries have the challenge of Malaria infection making the disease is a global threat to life across continents and borders.Malaria infection occurs in most of the tropicals countries of the world.

While P.vivax is the predominant specie in central America, P.falciparum is the dominant specie in Africa, new guinea and Haiti. P.ovale is a rare causative specia outside of Africa and in African countries where it occurs,it accounts for less than 1% of laboratory isolates.

P.malariea can be found in most parts of the malaria endemic zones particularly in most pars of subsaharran Africa though not very common.

In the the Indian subcontinent South America, eastern Asia, and Oceania the prevalence of p.falciparum and p.vivax are almost at equillibrum.

Malaria has a complex epidemiological profile many times with variable statistics within relatively small geographic areas.

Endemicity has been described in terms of the rates of parasitemia or the rate of palpable spleen in children between the ages of 2 and 9 .The terms hypoendemic (<10%), mesoendemic, (11–50%), hyperendemic (51–75%) and holoendemic(>75%) are used.For example in holoendemic areas over 75% of children between the ages of two and nine have malaria parasitaemia or palpable spleens as a result of recurrent malaria infection.However epidemiological profiling using these terms are rarely used for planning malaria control programmes.

In regions of the world where there is intense malaria transmission throughout the year (holoendemic and hyperendemic areas ) , such as parts of tropical Africa and coastal new guineas, people are bitten by malaria carrying mosquitoes more than once in a day and have repeated malaria infections throughout their lifetime. In these areas at risk groups such as children under five bear most of the burden of mortality and morbidity, individuals that survive severe fatal infections in childhood grow to become adults that have won herd immunity to severe forms of the disease and sometimes will have asymptomatic malaria. This pattern of constant,frequent and recurrent ,all year round infection is called stable transmission.

Unstable transmission occur in regions where malaria is hypoendemic. In these regions transmission pattern is low, unpredictable or focal , symptomatic disease is seen in people of all ages and full protective immunity is not acquired.

However in all regions where malaria is endemic, there is a direct correlation between the incidence of symptomatic malaria and mosquito breeding season. The raining season is the breeding season for mosquito species ,usually more cases of symptomatic malaria are recoreded over that period.

In areas of unstable malaria transmission, drastic adverse changes in socioecomic and environmental conditions can lead to an outbreak of malaria to epidemic proportions. A period of prolonged excessive rainfall after a drought, mass exodus of people like refugees or workers from high transmission areas to low transmission areas or a breakdown of malaria control policy and prevention strategies can lead to and intensify malaria epidemic. In such areas like northern India, Sri Lanka, Southeast Asia, Ethiopia, Eritrea, Rwanda, Burundi, southern Africa, and Madagascar, malaria transmission in epidemic proportions affects the young and old

It is not all the over 400 species of anopheles mosquito that transmit malaria, also those that do, do so to varying degree of efficiency . The major predictors of the epidemiology of malaria are three,; the density or number of anopheles mosquito in the region, the human biting behavior of the anopheles mosquito in the region and the life span of disease transmitting anopheles mosquito in the region.

Precisely, the incidence of  malaria is directly proportional to:
The density of the vector,
The square of the number of human bites per day per mosquito
The tenth power of the probability of the mosquito’s surviving for 1 day.

Clinical manifestation
Usually malaria presents initially with the symptom of fever that could be as high as 410C, this can be accompanied with drenching night sweats and rigors.However there may be a preceeding history of generalized body pains, headache, nausea, vomiting or diarrhea.The fever pattern could be continuos or intermittent with the tertian or quartian fever patters surfacing after a few days.
Signs of malaria can include,jaundice, enlarged spleen, conjunctival pallor, anemia,etc.

Severe malaria
In uncomplicated malaria where symptomatic patients can tolerate orals feeds and medicines, when promptly and appropriately treated the risk of mortality is as low as approximately 0.1%.

However in severe malaria, where the infection has caused vital organ dysfunction or the total number of parasitized red blood cells is greater than 2% (this corresponds to a parasite load of 1012 in adults, the mortality rate increases exponentially.

Some of the indicators of severe malaria and poor prognosis in P. falciparum infection are listed below:

Unarousable coma/cerebral malaria
Failure to localize or respond appropriately to noxious stimuli
coma persisting for >30 min after generalized convulsion

Arterial pH <7.25 or
plasma bicarbonate level of <15 mmol/L
venous lactate level of >5 mmol/L;
manifests as labored deep breathing, often termed “respiratory distress”

Severe normochromic, normocytic anemia
Pack cell volume of <15% or hemoglobin level of <50 g/L (<5 g/dL) with parasitemia level of >100,000/L

Renal failure
Urine output (24 h) of <400 mL in adults or <12 mL/kg in children;
serum creatinine level of >265 mol/L (>3.0 mg/dL)

Pulmonary edema/adult respiratory distress syndrome

Noncardiogenic pulmonary edema

Often aggravated by over hydration

Plasma glucose level of <2.2 mmol/L (<40 mg/dL)

Systolic blood pressure of <50 mmHg in children 1–5 years or <80 mmHg in adults;
core/skin temperature difference of >10°C
capillary refill >2seconds

Bleeding/disseminated intravascular coagulation
bleeding and hemorrhage from the gums, nose, and gastrointestinal tract and/or evidence of disseminated intravascular coagulation

Multiple Convulsions
More than two generalized seizures in 24 hours; signs of continued seizure activity sometimes subtle (e.g., tonic-clonic eye movements without limb or face movement)

Macroscopic black, brown, or red urine; not associated with effects of oxidant drugs and red blood cell enzyme defects (such as G6PD deficiency)


  • Impaired consciousness (arousable)
  • Unable to sit or stand without support
  • Extreme weakness
  • Prostration; inability to sit unaided
  • Hyperparasitemia
  • Parasitemia level of >5% in nonimmune patients (>20% in any patient)
  • Jaundice
  • Serum bilirubin level of >50 mmol/L (>3.0 mg/dL) if combined with other evidence of vital-organ dysfunction

Clinical features indicating  poor prognosis in severe falciparum malaria

  • Marked agitation
  • Hyperventilation (respiratory distress)
  • Hypothermia (<36.5°C)
  • Bleeding
  • Deep coma
  • Repeated convulsions
  • Anuria
  • Shock

Biochemical features indicating poor prognosis in severe falciparum malaria

  • Hypoglycemia (<2.2 mmol/L)
  • Hyperlactatemia (>5 mmol/L)
  • Acidosis (arterial pH <7.3, serum HCO3<15 mmol/L)
  • Elevated serum creatinine (>265 mol/L)
  • Elevated total bilirubin (>50mol/L)
  • Elevated liver enzymes (AST/ALT 3 times upper limit of normal, 5-nucleotidase )
  • Elevated muscle enzymes (CPK , myoglobin)
  • Elevated urate (>600 mol/L)

Hematologic indices indicating poor prognosis in severe falciparum malaria

  • Leukocytosis (>12,000/L)
  • Severe anemia (PCV <15%)
  • Decreased platelet count (<50,000/L)
  • Prolonged prothrombin time (>3seconds)
  • Prolonged partial thromboplastin time
  • Decreased fibrinogen (<200 mg/dL)

Parasitologic indices indicating poor prognosis in severe falciparum malaria

  • Hyperparasitemia:Increased mortality at >100,000/L, High mortality at >500,000/L
  • >20% of parasites identified as pigment-containing trophozoites and schizonts
  • >5% of neutrophils with visible pigment

Cerebral Malaria
coma is one of the signs of severe falciparum malaria and a pointer to poor prognosis, in spite of treatment cerebral malaria has a death rate of about 20% in adults and 15% in children.Features of delirium, abnormal behavior, irrational talk,obtundation should be prompty identified and taken seriously. Cerebral malaria could have a sudden or gradual onset usually following episode of convulsion.

Neurologic deficits and signs of meningeal irritation rarely occur though there might be some degree of resistance to flexion of the neck.

The eyes might be divergent with a positive pout reflex, other primitive reflexes are usually absent.

Except in deep coma corneal reflexes are usually normal

Muscles can be hyper or hypotonic. Tendon reflexes vary, the planter reflex could be extensor or flexor response,usually the abdominal and cremasteric reflexes are absent. Decorticate or decerebrate posturing can be seen.

About 15% of surferers have retinal hemmorrages, when the eyes are further probes with papillary dilation and indirect opthalmoscopy a retinal hemorrhage is detected in about 30-40 of cases. Other findings on fundoscopy can include presence ofpapilledema especially in children 8% this is rare finding in adults, cotton wool spots in less than 5% of cases, areas of discrete retinal opacification in 30 to 60% of cases ,decolarisation of whole or part the retinal vessel.

About 50% of children with cerebral malaria will have multiple generalized convulsions, others may experience subtle seizures that manifest as smacking of lips, repetitive tonic clonic eye movement, hypersalivation, twitching of the angle of the mouth,protruding tongue.

Approximately 15% of children who recover from cerebral malaria will suffer residual neurologic deficits, impaired cognition, cerebral palsy, cortical blindness, hearing impairements, persistent language deficit, are some of the complications that have been reported. An increase in the incidence of epilepsy and reduction in life expectancy have also been documented .In contrast to children neurologic sequalae is rare in adults occurring in less than 3% of cases.

Malaria in Pregnancy
In highly endemic areas malaria contributes significantly to infant and childhood mortality because of its association with causing low birth weight in newborns.Infected mothers in such areas are often asymptomatic despite the high load of parasitamia in the placenta circulation.

Because of reduction in the immune capacity HIV positive mothers have more predisposition to having malaria, their newborns are more likely to have congenital malaria infection and the reduction in birthweight due to malaria infection is further worsened in this group of women.

In areas of unstable malaria transmission pregnant women are at a very high risk of developing severe malaria with high level parasitaemia, complications like anemia, acute pulmonary oedma,hypoglycemia,fetal distress, preterm labour, still births or low birth weight infants can follow such severe infections.

Malaria in children under five

Children below age five are one of the most vulnerable and most hit by malaria.As a results of malaria infection About 285000 where reported to have died before their fifth birthdays in Africa in 2016.

In high transmission areas partial immunity to malariais acquired during the early childhood years , the implications of this is that severe disease that rapidly progresses to death occur in younger children who are yet to develop the herd immunity. Severe anemia, hypoglycemia, cerebral malaria are sinister conditions commonly seen in children but not adults.

The WHO recommends the following package of interventions for the prevention and treatment of malaria in children:
· use of long-lasting insecticidal nets (LLINs);
· in areas with highly seasonal transmission of the Sahel sub-region of Africa, seasonal malaria chemoprevention (SMC) for children aged between 3 and 59 months;
· in areas of moderate-to-high transmission in sub-Saharan Africa, intermittent preventive therapy for infants (IPTi), except in areas where WHO recommends administration of SMC;
· prompt diagnosis and effective treatment of malaria infections.


The diagnosis of malaria is done using in using microscopy or malaria rapid diagnostic test.
Microscopic diagnosis involves identifying malaria parasites on Giemsa stained thick or thin blood films.

Methods for the diagnosis of malaria

Thick blood film


  • Prepare thick blood smear
  • Leave thick blood smear to dry for 1-2 hours
  • Do not fix with methanol
  • When dry, stain with Giemsa, Field’s or Romanowsky stain.
  • Count number of asexual parasites per 200 WBCs (or per 500 at low densities).
  • Count gametocytes separately

Sensitive (0.001% parasitemia)
Species specific

Requires experience (artifacts may be misinterpreted as low-level parasitemia); underestimates true count

Thin blood film

  • Prepare a thin blood smear
  • When dry fix smear with 100% methanol
  • Stain with Giemsa, Field’s, or Romanowsky stain.
  • Count number of red blood cell containing asexual parasites per 1000 red blood cells.
  • In severe malaria, assess stage of parasite development and count neutrophils containing malaria pigment.
  • Count gametocytes separately


Species specific

In severe malaria, provides prognostic information

Insensitive to <0.05% parasitemia
Uneven distribution of P. vivax, as enlarged infected red cells concentrate at leading edge

PfHRP2 dipstick or card test
A drop of blood is placed on the stick or card, which is then immersed in washing solutions. Monoclonal antibody captures the parasite antigen and reads out as a colored band

Relatively cheap


Sensitivity similar to or slightly lower than that of thick films (~0.001% parasitemia)

Detects only Plasmodium falciparum

Remains positive for weeks after infection

Does not quantitate P. falciparum parasitemia

Plasmodium LDH dipstick or card test
A drop of blood is placed on the stick or card, which is then immersed in washing solutions. Monoclonal antibodies capture the parasite antigens and read out as colored bands. One band is genus specific (all malarias), and the other is specific for P. falciparum.


Sensitivity similar to or slightly lower than that of thick films for P. falciparum (~0.001% parasitemia)

Slightly more difficult preparation than PfHRP2 tests

May miss low-level parasitemia with P. vivax, P. ovale, and P. malariae and does not speciate these organisms

Does not quantitate P. falciparum parasitemia

Microtube concentration methods with acridine orange staining
Blood is collected in a specialized tube containing acridine orange, anticoagulant, and a float. After centrifugation, which concentrates the parasitized cells around the float, fluorescence microscopy is performed.

Sensitivity similar or superior to that of thick films (~0.001% parasitemia

Ideal for processing large numbers of samples rapidly

Does not speciate or quantitate

Requires fluorescence microscopy

Treatment of uncomplicated malaria
In susceptiple strains of P. vivax,P. ovale and P. malariae chloroquine is the drug of choice, though is increasing reistance in some strains of P.Vivax.A succesful course of chloroquine treatment if followed by a two to three week course of oral primaquine usually 15mg daily to eradicate hepatic hypnozoites and prevent relapse in P. vivaxor P. ovale infections

Artemisinin based therapy is the drug of choice in uncomplicated and severe P.falciparum malaria in adults and children.

The World Health Organisation (WHO) has adviced that the atemisinin derivatives should not be prescribed as monotherapy in order to prevent resistance, five different fixed dose combinations are available in the market, the choice of the partner drug used is based on the pattern of drug resistance in a particular setting.

Guidelines for the treatment  of severe falciparum malaria.

  • All adults and children with severe malaria must receive intravenous or intramuscular artesunate for a minimum period of 24hrs
  • Once a patient has gotten 24hours of parenteral therapy and can tolerate orally, treatment is completed with 3 days of ACT (Artemisinin Based Combination Therapy) tablets.
  • Children weighing < 20 kg should receive a higher dose of artesunate (3 mg/kg body weight per dose) than larger children and adults (2.4 mg/kg body weight per dose) to ensure equivalent exposure to the drug.
  • If parenteral artesunate is not available, artemether is preferred to quinine for treating children and adults with severe malaria.
  • There should be provision of intensive care facilities like mechanical ventilation and dialysis for patients.
  • Severe anaemia may require transfusion.
  • Pulmonary oedema and prerenal failure are common hence careful monitoring of fluid balance is crucial to successful treatment
  • Hypoglycaemia can be induced both by the overwhelming malaria infection and by quinine administeration.
  • Superimposed bacterial infection is common.In very heavy infections (parasitaemia>10%), there maybe a need for exchange transfusion, if the facilities are available.

Complications of malaria
Acute renal failure
Acute pulmonary oedema
Haematological abnormality
Liver dysfunction
Tropical splenomegaly
Quartan malarial nephropathy
Epstein Barr virus infection
Burkitt lymphoma

Malaria prevention and control

Malaria prevention and control involves early diagnosis and treatment of confirmed cases, control of the vector which is mosquitoes, protection of individuals from mosquito bites such as using insecticide treated nets.

African woman posing with her Insecticide Treated Mosquito Net

Eradication of mosquitoes is achieved by spraying insecticides or altering their habitat such as draining marshy areas.

The emergence of mosquito resistance to insecticides and parasite resistance to antimalarials has posed a dual chllenge to the eradication of malaria .

People without immunity traveling to malaria endemic areas are advised to use mosquito repellants. Antimalaria prophylaxis like proguanil should also be used though the drugs do not give 100% protection.

Author: Faisol Oladosu

Faisol - founder of

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