Malaria

Malaria is a serious and potentially fatal disease(life-threatening) caused by parasites that are transmitted to humans through the bites of infected female Anopheles mosquitoes. This disease can be both prevented and treated. Five different parasite species cause malaria in humans, with Plasmodium falciparum and Plasmodium vivax being the most dangerous.

Malaria is caused by a parasite and transmitted by Anopheles mosquitoes. Not all Anopheles mosquitoes carry malaria, but if they bite an infected person, they can become carriers. When these infected mosquitoes bite another person, they spread malaria, continuing the transmission cycle.

Pathophysiology

Female Anopheles mosquitoes transmit these parasites(Plasmodium species e.g.P. falciparum, P. ovale, P. vivax, P. malariae, and P. knowlesi) during blood meals, introducing sporozoites into the human bloodstream. Sporozoites reach the liver within an hour, invade hepatocytes, and multiply into merozoites. In active infections, merozoites reenter the bloodstream, infect red blood cells, consume haemoglobin, and develop from immature trophozoites to either mature trophozoites or gametocytes. Mature trophozoites form schizonts, which disrupt red blood cells, causing cell lysis.

The release of free heme activates endothelial cells. Untreated malaria can last 2 to 24 months. P. vivax and P. ovale can remain dormant in the liver and reactivate later. Rarely, P. falciparum can also reactivate years after initial infection.

Pathogenesis involves toxin-induced IFN-gamma and TNF-alpha secretion, with monocyte and macrophage activity in the spleen. Adaptive immunity involves class switching of CD4-positive lymphocytes. TNF suppresses blood cell formation, contributes to anaemia, and causes liver and spleen enlargement.

Severe malaria is associated with low arginine, low nitric oxide, and high arginase activity. The parasite’s arginase enzyme reduces arginine levels, decreasing nitric oxide production, which can lead to pulmonary hypertension and myocardial stress. Treatments might include peripheral arginine or inhaled nitric oxide.

 

symptoms

Malaria symptoms can vary from mild to severe and may even lead to death. Early symptoms include:

  • Fever and flu-like illness
  • Chills
  • Headache
  • Jaundice is common
  • Anaemia
  • hepatomegaly
  • muscle aches
  •  fatigue
  • Nausea
  •  Vomiting
  •  diarrhoea

If not treated promptly, the infection can escalate to severe symptoms such as:

  • Seizures
  • Mental confusion
  • Coma

Diagnosis

  • Microscopy: Light microscopy remains the gold standard for diagnosing malaria. It offers high sensitivity and specificity when performed correctly, allowing for parasite quantification, species identification, and monitoring of treatment response. However, it requires well-trained staff, quality infrastructure, and maintenance of equipment.
  • Rapid Diagnostic Tests (RDTs): RDTs are widely used due to their simplicity and rapid results, making them suitable for decentralized settings without access to microscopy. They detect parasite-specific antigens in blood samples, with some tests capable of identifying multiple malaria species. RDTs are essential for quick diagnosis and prompt treatment initiation, particularly in remote areas.
  • Molecular Diagnostic Techniques: Techniques like PCR and loop-mediated isothermal amplification (LAMP) offer high sensitivity and are valuable for detecting low-density infections and monitoring drug resistance. However, they are currently not practical for routine clinical use in malaria-endemic regions due to cost, technical requirements, and infrastructure limitations.
  • Immunodiagnosis: Antibody detection methods lack the sensitivity and specificity needed for diagnosing acute malaria infections and are primarily used for epidemiological studies rather than clinical management.

Treatment

Malaria is treated with medications designed to eliminate the malaria parasite. The choice of treatment depends on the specific type of parasite causing the infection:

  •  P. falciparum, the preferred treatment for cases resistant to chloroquine is Artemisinin-based combination therapy (ACT), which includes medications like artemether-lumefantrine (Coartem), artesunate-mefloquine, and dihydroartemisinin-piperaquine.
  • P. vivax and P. ovale infections are typically treated with chloroquine where it remains effective. Primaquine is often added to prevent relapses. It can also be combined with chloroquine phosphate or hydroxychloroquine if the infection is sensitive to chloroquine.
  • uncomplicated malaria, alternative treatments include atovaquone-proguanil (Malarone), quinine sulphate combined with doxycycline, tetracycline, or clindamycin, as well as hydroxychloroquine.

Prevention:

  • Consult Your Healthcare Provider: Before travelling to malaria-prone areas, discuss preventive medications with your healthcare provider.
  • Avoid High Mosquito Activity: Stay away from areas with high mosquito activity, particularly during late evening and night when Anopheles mosquitoes are most active.
  • Use EPA-Approved Bug Spray: Apply a bug spray that is approved by the Environmental Protection Agency (EPA).
  • Wear Protective Clothing: Opt for loose-fitting, long-sleeved shirts, pants, and socks.
  • Keep Mosquitoes Out: Ensure windows and doors are closed or covered with screens to prevent mosquitoes from entering your home.
  • Repair Broken Screens: Fix any broken screens on windows, doors, porches, and patios to maintain a mosquito-free environment.

  Vaccine

  • Two vaccines are recommended for children in moderate to high malaria transmission areas.
  • They reduce uncomplicated malaria by approximately 40%, severe malaria by about 30%, and all-cause mortality by 13%.
  • Effective delivery requires integration with other interventions such as insecticide-treated bed nets (ITNs) and case management.
  • Community healthcare workers play a crucial role in administering these vaccines to children.

Two vaccines ⬇️

RTS, S

RTS, S/AS01 (Mosquirix) is the first malaria vaccine approved for public use. Developed by PATH Malaria Vaccine Initiative and GlaxoSmithKline, with support from the Bill and Melinda Gates Foundation, it’s a recombinant vaccine containing the Plasmodium falciparum circumsporozoite protein (CSP). This protein, derived from the parasite’s pre-erythrocytic stage, triggers antibody production to prevent hepatocyte invasion and stimulates a cellular response for infected hepatocyte destruction. RTS,S overcame initial immunogenicity challenges by fusing CSP with a hepatitis B virus surface antigen, enhancing its potency. Clinical trials showed promising results, providing protective immunity in most volunteers challenged with P. falciparum.

 R21/Matrix-M 

The R21/Matrix-M malaria vaccine, developed through collaboration involving the Jenner Institute at the University of Oxford, Kenya Medical Research Institute, London School of Hygiene and Tropical Medicine, Novavax, and the Serum Institute of India, has demonstrated 77% efficacy in initial trials. This makes it the first malaria vaccine to meet the WHO’s efficacy goal of at least 75%. The vaccine uses a higher proportion of the circumsporozoite protein (CSP) antigen compared to RTS,S and incorporates a HBsAg-linked recombinant structure without excess HBsAg. It includes the Matrix-M adjuvant, also used in the Novavax COVID-19 vaccine.