Malaria: Signs, Symptoms and Treatment

Malaria is a mosquito-borne blood disease transmitted by the bite of an infected female anopheles mosquito. Malaria is caused by infection of red blood cells with a protozoan parasite of the genus Plasmodium. Plasmodium falciparum is the commonest and is associated with significant morbidity and mortality.

The parasites are innoculated into the human host by a feeding of a female anopheles mosquito.

The other species are Plasmodium malariae, Plasmodium vivax, Pplasmodium ovale and plasmodium knowlesi.

Infection with P. vivax and P. ovale can be associated with well-defined malarial paroxysms, in which fever spikes, chills and rigors occur at regular intervals.
At this stage, with no evidence of vital organ dysfunction, the case-fatality rate is low provided prompt and effective treatment is given.

Signs and Symptoms

The symptoms of uncomplicated malaria can be rather non-specific and the diagnosis can be missed.

Since untreated malaria can progress to severe forms that may be rapidly fatal, malaria should always be considered in patients who have a history of exposure.

The most frequent symptoms include fever and chills, which can be accompanied by headache, myalgias, arthralgias, weakness, vomiting, and diarrhea.

Other clinical features include splenomegaly, anemia, thrombocytopenia, hypoglycemia, pulmonary or renal dysfunction, and neurologic changes.

The clinical presentation can vary substantially depending on the infecting species, the level of parasitemia, and the immune status of the patient.

Infections caused by P. falciparum are the most likely to progress to severe, potentially fatal forms with central nervous system involvement into what is known as cerebral malaria, acute renal failure, severe anemia, or acute respiratory distress syndrome.

Other species can also have severe manifestations.

Complications of P. vivax malaria include splenomegaly, and those of P. malariae include nephrotic syndrome.

In classifying the presentation of malaria as complicated or uncomplicated, patients may present with the following features.

Uncomplicated Malaria

Classically, malaria presents with paroxysms of fever, chills, rigours, and sweating.

Other features include malaise, headache, myalgia, joint pains, refusal to feed, nausea, vomiting, abdominal discomfort, and diarrhoea.

Severe Malaria

Severe malaria presents with a combination of most of the above plus either one or more of the following features

1. 1. 1. Parasitaemia >5% or >200,000 parasites per µl of blood in high transmission area or >100,000 parasites per µl of blood in the low transmission area.
      1. Anaemia Hb <5gm%
      2. Cerebral malaria manifesting as confusion, stupor, convulsions or coma
      3. Jaundice
      4. Hyperpyrexia, temperature >39oC
      5. Hypoglycaemia (blood sugar <2.2mmol/L)
      6. Pulmonary oedema
      7. Disseminated intravascular coagulopathy (DIC – spontaneous bleeding)
      8. Malaria haemoglobinuria (Coca-cola coloured urine)
      9. Oliguria
      10. Hypovolaemic shock
      11. Fluid electrolyte imbalance

Diagnostic Investigations

In outpatient department cases

• Thick blood smear for malaria parasites (several slides may need to be done)

In inpatient cases

• Thin blood smear for parasite count, species identification, and red blood cell morphology:

Haemoglobin levels,

Blood sugar levels,

Urinalysis.

A negative slide does not necessarily rule out malaria. Where cerebral malaria is suspected, begin appropriate therapy promptly.

Exclude other diseases, e.g., meningitis, which may present with similar features. It is recommended that you do not assume a positive slide explains the cause of a febrile illness: 20–30% of the normal population in endemic parts will have a positive slide for malaria parasites without symptoms and signs of malaria.

Treatment of malaria

The objective of treating uncomplicated malaria is to cure the infection. This is important as it will help prevent progression to severe disease (complicated malaria) and prevent additional morbidity associated with treatment failure.

Cure of the infection means eradication from the body of the infection that caused the illness. In treatment evaluations in all settings, emerging evidence indicates that it is necessary to follow patients for long enough to document cure.

The public health goal of treatment is to reduce transmission of the infection to others, i.e. to reduce the infectious reservoir.

A secondary but equally important objective of treatment is to prevent the emergence and spread of resistance to anti-malarials. Tolerability, the adverse effect profile and the speed of therapeutic response are also important considerations.

Uncomplicated Malaria

These cases are treated as outpatients.

The current recommended treatment of patients with uncomplicated malaria is a combination of artemether-lumefantrine. This is available as a fixed-dose combination with a tablet containing 20mg of artemether and 120mg of lumefantrine.

Treat adults with a 6-dose regimen of 4 tablets STAT, then 4 on hours 8, 24, 36, 48, and 60 hours.

Should the patient deteriorate clinically at any time or symptoms persist 3–14 days after initiation of treatment, this should be considered as treatment failure.

Treat such patients with quinine. Tablets come in 200mg or 300mg preparations. The dose is approximately 10mg/kg of body weight 8 hourly for 7 days.

Recommended second line drugs are dihydroartemisinin plus piperaquine.

Severe Malaria

Prompt diagnosis and management of the specific complication are vital. Quinine is the recommended treatment for severe malaria.

Give quinine injection as a loading dose of 20mg/kg IM then continue with a maintenance dose of 10mg/kg 8 hourly.

OR Give artemether as loading dose 3.2mg/kg IM injection, then 1.6mg/kg maintenance dose until the patient can take oral therapy, then put on a full course of AL

General Management

Reduce the temperature if hyperpyrexia if present and maintain fluid and electrolyte balance especially if there has been a significant fluid loss.

Monitor output. Output should be at least 30ml per hour. if hydration is inadequate and oliguria persists give frusemide 40–80mg IV STAT.

To manage convulsions: Use diazepam 0.3mg/kg IV/IM OR Rectal 0.5mg/kg OR Paraldehyde 0.2ml/kg IM.

In cases of hypoglycaemia, Monitor blood glucose regularly. Large doses of dextrose may be required 25% 2ml/kg or 50% 1ml/kg.

Anaemia: Monitor Hb regularly. Transfuse if Hb is less than 5g% AND patient develops cardiorespiratory distress (grunting, nasal flaring, chest indrawing, heart failure).

Check blood slide for malaria parasites daily to confirm if parasitaemia is falling.

Specific Management

The management of adults with severe malaria must be appropriate to each complication that develops. Quinine is not contraindicated in pregnancy. Fluid and antimalaria drugs are given for children.

IV quinine should be given as follows:

First dose 20mg/kg in ½ litre of fluid in 5% dextrose given over 4 hours (max 1,200mg). Then give 10mg/kg in ½ litre of fluid over 4 hours (max 600mg) 8 hours after commencing the initial dose. Repeat 10mg/kg 8 hourly until the patient can take orally.

Change to oral artemeter lumefantrine full dose or oral quinine to complete 7 days of therapy.

Assess fluid regularly, including urine output.

Monitoring response

It is similar to that for children, with special attention to the complications. If the patient cannot be weighed, the loading dose should be 900mg, followed by 600mg 8 hourly.

Monitor for and correct hypoglycaemia with 50% dextrose (1ml/kg). NB: Each infusion of quinine should be given over 4 hours.

Use quinine IM if IV drip cannot be monitored or fail to get IV access. Quinine hydrochloride may be given IM in emergencies

The dose for adults above 60kg should not exceed 600mg. Quinine hydrochloride may be given IM in emergencies.

Oral quinine may be introduced intragastrically by nasogastric tube in situations when parenteral quinine is not available.

Look out for renal failure.

Chemoprophylaxis

Anti-malaria prophylaxis should be given to the following groups when going to malaria-prone areas. All non-immune visitors to malarious areas;

Long-term residence >4 weeks
Short-term residence <4 weeks

Patient with sickle cell disease and thalassaemia

Children with impaired immunity (e.g., HIV, leukaemia)

Patients with hyperimmune malaria syndrome, leukaemia or splenectomy

Pregnant women (minimum of 2 IPT doses a month apart)

Chemoprophylaxis regimen

Current recommended antimalarial prophylaxis for those at risk is mefloquine 250mg given weekly starting 2 weeks before travel to a malaria endemic area and continued for up to 4 weeks after return to a non malarious area.