QuestionSBA
QuestionChoice
Hydroxychloroquine is a drug used in the treatment of systemic lupus erythematosus. It may also be used instead of chloroquine to treat malaria, however, chloroquine-based therapies are no longer recommended as the first line due to increasing levels of resistance. Instead, artemisinin-based combination therapy is recommended as a first-line treatment by the WHO.
10000495
e
Hydroxychloroquine
QuestionChoice
Symptomatic management alone is not appropriate management for malaria. Paracetamol is recommended for use to manage fever in malaria, but additional treatment to target the parasite is recommended by the WHO.
10000494
d
Symptomatic management
QuestionChoice
This patient is suffering from malaria. Malaria is a parasitic infection caused by *Plasmodium* parasites and transmitted by the *Anopheles* mosquito. Malaria classically presents with a high fever, headache, fatigue, myalgia/arthralgia as well as signs and symptoms of red blood cell destruction (e.g. anaemia, jaundice). Artemisinin-based combination therapy (ACT) is the treatment of choice for malaria. Chloroquine-based therapies may still be used but due to the increase in chloroquine resistance across many endemic countries, the WHO recommend the use of ACT instead.
10000491
a
Artemisinin-based combination therapy
QuestionChoice
Praziquantel is the treatment of choice for schistosomiasis. Schistosomiasis is a parasitic infection that typically manifests in the genitourinary tract or intestinal tract. It most commonly presents with fever, rash, abdominal pain and urinary symptoms. Schistosomiasis would not present with trophozoites on blood film and therefore can be ruled out.
10000493
c
Praziquantel
QuestionChoice
Although chloroquine was previously the mainstay of malaria management, recent rises in chloroquine resistance have resulted in the WHO recommending the use of artemisinin-based combination therapy in place of chloroquine.
10000492
b
Chloroquine
Concept
Chapter
# Summary

Malaria is caused by protozoan parasites of the Plasmodium genus, with five species affecting humans: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Predominantly found in tropical and subtropical regions, malaria is a significant global health concern and the most common imported tropical disease in the UK. The parasite's life cycle involves humans and female Anopheles mosquitoes, with human infection comprising liver and blood stages. Symptoms result from blood-stage parasites and can vary by species, with P. falciparum having a 7-30 day incubation period. Risk factors for severe disease include pregnancy, age extremes, and immunosuppression. Diagnosis relies on blood films and rapid diagnostic tests. Treatment depends on the species and severity, with artemisinin-based therapies commonly used. Prevention includes avoiding travel to endemic areas, mosquito bite prevention, and chemoprophylaxis. Malaria is notifiable, necessitating reporting to health authorities.


# Definition


Malaria is a disease caused by protozoan parasites of the Plasmodium genus. The different malaria species are:

* *P. falciparum* (the most pathogenic species)
* *P. vivax*
* *P. ovale*
* *P. malariae*
* *P. knowlesi*

# Epidemiology

Malaria is typically found in the tropics and subtropics, and contributes to significant morbidity and mortality globally. It is the most common imported tropical disease in the UK, usually on return from travel.


# Aetiology


The parasitic life cycle of malaria involves a cyclical infection of two hosts: humans and female Anopheles mosquitoes. Infection in humans occurs in two stages: the liver stage and the blood stage. The clinical signs and symptoms of the disease are due to blood-stage parasites and tend to occur at different times depending on the species. *Plasmodium falciparum* has an incubation period of 7-30 days.

Following the bite of an infected female Anopheles mosquito, parasites, known as sporozoites, are inoculated into the human host, where they transit in the bloodstream to the liver. Sporozoites initially establish infection in hepatocytes, where they replicate and mature into hepatic schizonts. These subsequently rupture and release a form of parasite known as a merozoite into the bloodstream.

Merozoites infect erythrocytes, forming trophozoites that reproduce asexually and mature into blood-stage schizonts, which also rupture, causing the further release of merozoites. Some trophozoites differentiate into male or female gametocytes, which may be ingested by their second host, the Anopheles mosquito, in subsequent blood meals. Gametocytes reproduce within the stomach of the mosquito, where they form oocysts which grow and release sporozoites, which travel to the mosquito's salivary glands to further perpetuate the cycle of further inoculation into a new human host.

The clinical manifestations of the disease are due to blood-stage parasites, which cause the accumulation of toxic substances and waste during their development in erythrocytes. Lysis of red blood cells results in the releasing these factors and potent inflammatory immune responses. The incubation period until symptoms appear tends to vary between 7 to 30 days. 

**Risk factors for severe disease:**

- Pregnancy
- Children
- Elderly
- Complex comorbidities
- Immunosuppression

# Signs & Symptoms

Initial symptoms of malaria are quite non-specific. These include:

* Fevers which may be cyclical, sweats and chills
* Headache, malaise, aches & pains
* Abdominal pain, nausea & vomiting, diarrhoea
* Patients may have splenomegaly, jaundice, hypotension, pallor and reduced urine output


Features of severe malaria relate to the disease process or complications:

- Abnormal behaviour, seizures or altered consciousness suggest cerebral malaria
- Parasitaemia >2%, severe anaemia or haemoglobinuria
- Hypoglycaemia, metabolic acidosis, hypovolaemia
- Temperature >39C
- Acute respiratory distress syndrome, disseminated intravascular coagulation or shock
- Renal impairment


# Differential Diagnosis

- Infections encountered in the UK e.g. meningitis, sepsis, pneumonia, viral illness, UTI, hepatitis, HIV
- Non-infectious causes of fever e.g. lymphoma
- Other travel-associated infections e.g. viral haemorrhagic fevers, enteric fever, Dengue, Rickettsia, Trypanosomiasis, Rabies


# Investigations

Thick and thin blood films are the gold-standard method of diagnosing malaria. The thick film identifies the presence of parasites, and the thin film determines the species. If negative, films should be repeated.

Rapid diagnostic tests can also be used but do not replace the need for blood films.

Other important investigations include:

- FBC & film, clotting, U&E's, LFT's, glucose measurement
- Urine dip ± culture
- ABG if severe symptoms

Other investigations to consider include blood cultures, stool culture, chest X-ray and lumbar puncture.

# Management

Patients with malaria usually need to be admitted to hospital as they can deteriorate very quickly. A-E assessment is required for acutely unwell patients and specialist management should be sought early, regardless.

Definitive treatment for malaria depends on the species identified and the presence of complications. First-line treatments are:

- Uncomplicated falciparum: artemisinin-based combination (Artemether with lumefantrine) therapy
- Uncomplicated non-falciparum: artemisinin-combination therapy or chloroquine
- Severe falciparum: IV artesunate

Patients will also require supportive care and antipyretics. In severe cases, ICU admission may be indicated.

Malaria is a notifiable disease and all cases should be reported to the local health protection team in the first instance.

**Malaria prevention**

A careful risk assessment needs to be undertaken before any travel to a malaria-endemic area. Interventions to avoid infection include:

- Avoidance of travel - particularly those who are at higher risk of severe infection
- Measures to avoid mosquito bites - avoiding exposure at dusk & down, mosquito nets & screens, repellant, loose clothing
- Chemoprophylaxis - drugs available include chloroquine, mefloquine and doxycycline, all of which have pro's and cons and, as such, should be an individualised decision
- Education about malaria, its symptoms and seeking medical attention early. Standby emergency medication may be prescribed if the person is far from medical care.


# NICE Guidelines

[NICE CKS: malaria prophylaxis](https://cks.nice.org.uk/topics/malaria-prophylaxis/)

[NICE CKS: Malaria](https://cks.nice.org.uk/topics/malaria/)

# References

[BNF: Malaria, treatment](https://bnf.nice.org.uk/treatment-summaries/malaria-treatment/#advice-for-travellers)

[UK malaria treatment guidelines 2016](https://www.journalofinfection.com/article/S0163-4453(16)00047-5/fulltext)

[British Society for Haematology guidelines for the laboratory diagnosis of malaria](https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.18092)

[Patient.info: Malaria](https://patient.info/doctor/malaria-pro#malaria-epidemiology)
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Malaria
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Infectious Diseases
12645
A 53-year-old female presents to the Emergency Department with a 3-day history of high fever, headache, arthralgia, malaise, and fatigue.

The patient returned 1 week ago from Zimbabwe where she was visiting family.

Examination reveals a temperature of 39C and a full blood count reveals anaemia and thrombocytopenia. Thick and thin blood smears reveal the presence of trophozoites in the blood.

Which of the following is the best treatment for this patient?
a