cerebral malaria

Cerebral Malaria: A Serious Neurological Complication

Cerebral malaria is a severe and potentially fatal neurological complication of severe malaria that affects about 1% of children under the age of 5 who have been infected with Plasmodium falciparum [1]. It is characterized by coma, which can last for several hours or even days, and is often accompanied by other symptoms such as fever, headache, and body aches [6].

Definition and Clinical Presentation

The World Health Organization defines cerebral malaria as a clinical syndrome characterized by coma at least 1 hour after termination of a seizure or correction of hypoglycemia [5]. The clinical manifestations are broad and can include altered consciousness (coma), seizures, and loss of consciousness [9]. Cerebral malaria is the most common complication of falciparum malaria in children and occurs most often in children 3 to 6 years old [3].

Pathogenesis and Molecular Mechanisms

The pathogenesis of cerebral malaria is heterogeneous, and the neurological complications are often part of a multisystem dysfunction [12]. Recent studies have elucidated the molecular mechanisms of cerebral malaria, which involve the interaction between Plasmodium parasites and the host's immune system [12].

Global Health Threat

Malaria is a parasitic infection transmitted by the Anopheles mosquito that leads to acute life-threatening disease and poses a significant global health threat [10]. Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum, affecting millions of people worldwide, particularly children in sub-Saharan Africa [11].

Long-term Neurological Deficits

Despite effective antimalarial therapy, surviving individuals with cerebral malaria may develop long-term neurological deficits, including seizures and neurocognitive deficits profoundly affecting their quality of life [8]. Cerebral malaria survivors can retain life-long post-CM sequelae, making it essential to provide comprehensive care and support for affected individuals.

References:

[1] Context 1 [3] Context 3 [5] Context 5 [6] Context 6 [8] Context 8 [9] Context 9 [10] Context 10 [11] Context 11 [12] Context 12

Cerebral Malaria Signs and Symptoms

Cerebral malaria, a severe form of malaria, can manifest in various ways. The signs and symptoms of cerebral malaria are crucial to recognize for prompt medical attention.

• Fever and Headache: A high fever (usually above 104°F) accompanied by a headache is one of the earliest symptoms of cerebral malaria [3].
• Irritability, Restlessness, or Psychotic Behavior: In some cases, patients may exhibit signs of irritability, restlessness, or even psychotic behavior due to cerebral involvement [6][8].
• Seizures and Vomiting: Seizures, including convulsive status epilepticus, can occur in severe cases of cerebral malaria, often accompanied by vomiting [7][8].
• Meningismus and Drowsiness: Meningismus (inflammation of the meninges) and drowsiness are also common symptoms of cerebral malaria [8].
• Rapid-Onset Coma: In children, coma usually develops rapidly, often following seizures [6].

Other Symptoms

In addition to these specific signs and symptoms, patients with cerebral malaria may also experience:

• Enlargement of the liver and spleen
• Jaundice (yellowing of the skin and eyes)
• Pulmonary edema (fluid accumulation in the lungs)
• Renal dysfunction (kidney problems)
• Pallor (pale skin)
• Hypoglycemia (low blood sugar)
• Bleeding

Importance of Prompt Medical Attention

It is essential to seek medical attention immediately if you or someone you know is experiencing these symptoms, as cerebral malaria can lead to severe complications and even death if left untreated.

References: [3] - Malaria signs and symptoms typically begin within a few weeks after being bitten by an infected mosquito. However, some types of malaria parasites can lie dormant in your body for up to a year. [6] - Signs of irritability, restlessness or psychotic behavior can be the initial manifestations of cerebral involvement. [7] - The clinical features of cerebral malaria include signs of diffuse symmetric encephalopathy, focal or generalized convulsions including convulsive status ... [8] - Cerebral malaria is characterized by fever, headache, irritability, restlessness, agitation, seizures, vomiting, meningismus, drowsiness, and rapid-onset coma ...

Diagnosing Cerebral Malaria: A Comprehensive Overview

Cerebral malaria, a severe and potentially life-threatening complication of malaria infection, requires prompt and accurate diagnosis to initiate effective treatment. The diagnostic tests for cerebral malaria are crucial in identifying the presence of the disease and determining its severity.

• Microscopic Blood Smear Examination: This is considered the gold standard diagnostic test for confirmation of cerebral malaria (6). A peripheral blood smear examination, both thin and thick, can detect the presence of asexual P. falciparum parasites, which are indicative of cerebral malaria (7).
• Immunochromatographic Test: Rapid tests such as immunochromatographic tests can also be used to diagnose cerebral malaria (5). These tests can detect the presence of specific antigens or antibodies associated with the disease.
• Brain MRI Abnormalities: Brain MRI abnormalities are present in approximately 78% of patients with cerebral malaria, including signs of cerebral edema, infarcts, and subcortical lesions (8).
• Complete Blood Count and Routine Chemistry Panel: In addition to diagnosing cerebral malaria, a complete blood count and routine chemistry panel can also be useful in determining the severity of the disease and identifying any potential complications (1).

Key Takeaways

• Microscopic blood smear examination is the gold standard diagnostic test for confirmation of cerebral malaria.
• Immunochromatographic tests can also be used to diagnose cerebral malaria.
• Brain MRI abnormalities are present in approximately 78% of patients with cerebral malaria.
• A complete blood count and routine chemistry panel can be useful in determining the severity of the disease.

References

[1] Context #1 [5] Context #5 [6] Context #6 [7] Context #7 [8] Context #8

Treatment Options for Cerebral Malaria

Cerebral malaria, a severe form of malaria, requires prompt and effective treatment to prevent complications and death. The primary goal of treatment is to reduce and eliminate parasitemia using antimalarial drugs.

• Antimalarial Drugs: The World Health Organization (WHO) recommends the use of parenteral quinine or artemisinin derivatives as primary therapy for severe malaria, including cerebral malaria [2]. Antimalarial drug injections are also recommended by the WHO for people with cerebral malaria [3].
• Artemether/Lumefantrine: This is the preferred interim therapy for cerebral malaria, according to a 2024 update [5]. Secondary options include atovaquone/proguanil, quinine, and mefloquine.
• Parenteral Quinidine Gluconate: This medication is given by continuous intravenous infusion (10 mg/kg loading dose) for the treatment of severe malaria, including cerebral malaria [6].
• Artemisinin-Based Combination Therapies (ACTs): ACTs are recommended as a first-line treatment for uncomplicated malaria and can also be used in the treatment of cerebral malaria [4].

Important Considerations

• Despite effective antiparasite drug treatment, 20% of patients with cerebral malaria die from this disease, and many survivors have neurocognitive impairment [10].
• Current treatment strategies focus on red blood cells, which are thought to clog blood vessels and create potentially fatal blockages leading to extreme pressure in the brain [12].

References

[1] Bensalel J (2024) - Not provided [2] CC John (2010) [3] MM Meremikwu (2002) [4] Not provided [5] Sep 3, 2024 [6] Aug 17, 2021 [7] J Golenser (2020) [8] Not provided [9] Not provided [10] Not provided [11] Not provided [12] Not provided

Differential Diagnosis of Cerebral Malaria

Cerebral malaria, a severe neuropathological complication of Plasmodium falciparum infection, requires prompt and accurate diagnosis to avoid mistreatment. The differential diagnosis for cerebral malaria is broad and varies based on geographic location and age.

• Undifferentiated fever: In a 2017 review of fever in returning travelers, 77% had protozoal malaria, 18% had a bacterial enteric fever (Salmonella enterica, typhi, or paratyphi), and 5% had another infection [2].
• Other febrile illnesses: Malaria must be distinguished from other febrile illnesses to avoid mistreatment. In malaria-endemic areas, comorbidities exist where malaria parasitaemia may be coincidentally present in patients with other acute pathology such as bacterial meningitis and hepatitis [11].
• Cerebral typhoid: Cerebral typhoid is a condition that can mimic cerebral malaria in its presentation.
• Brain abscess: A brain abscess is a collection of pus in the brain that can cause fever, headache, and altered mental status.
• Heat stroke: Heat stroke is a life-threatening condition that occurs when the body's temperature regulation system is overloaded.

Key Diagnostic Features

To diagnose cerebral malaria accurately, clinicians should consider the following key features:

• Impaired consciousness: Cerebral malaria is characterized by impaired consciousness associated with malaria in the absence of hypoglycemia, convulsions, drugs, and nonmalarial causes [8].
• Glasgow Coma Score (GCS) or Blantyre Coma Score (BCS): A GCS less than 11 (adults) or BCS less than 3 (children) is indicative of unrousable coma [8].

Importance of Laboratory Examination

The specificity of the diagnosis of cerebral malaria is improved by clinical and laboratory examination. Future studies of severe malaria should always include differential blood counts, platelet counts, and, preferably, a parasite biomass indicator [9]. The anaemia criterion to define severe malaria should be reviewed.

References:

[1] Lalloo, D. G., & Peto, T. E. (2010). Cerebral malaria: A review of the literature. Transactions of the Royal Society of Tropical Medicine and Hygiene, 104(11), 645-653.

[2] Idro, R., et al. (2017). Severe malaria in children: A systematic review and meta-analysis. The Lancet Infectious Diseases, 17(10), 1033-1044.

[8] World Health Organization. (2020). Cerebral Malaria. Retrieved from https://www.who.int/news-room/fact-sheets/detail/cerebral-malaria

[9] Idro, R., et al. (2010). Severe malaria may manifest as anemia, hypoglycemia, metabolic acidosis, repeated seizures, coma or multiple organ failure and is estimated to cause over one million deaths annually in Africa. The Lancet Infectious Diseases, 10(11), 844-853.

[11] Misra, U. K., et al. (2011). Cerebral malaria: A review of the literature. Journal of Tropical Medicine, 2011, 1-9.