Amivas Ireland Ltd is a wholly owned subsidiary of Amivas Inc. focused on the development, manufacturing, and commercialization of therapeutics for the treatment of infectious diseases for the European and UK markets.
Amivas Inc was formed in response to the urgent need for a US -based firm to assume responsibility for the manufacture and distribution of Artesunate for Injection, for severe malaria after quinidine gluconate was discontinued by the manufacturer within the USA.
For more information about Amivas Ireland Ltd and Artesunate for Injection, please see our most recent press release.
Read about a new severe malaria product and how to order. This innovative malaria treatment is our first registered medication for slow bolus intravenous delivery. Artesunate for Injection is administered during hospitalization. It is suitable for the treatment of patients with severe malaria. It is recommended that Artesunate Amivas should be used to treat patients with severe malaria only after consultation with a physician with appropriate experience in the management of malaria.
Malaria, symptoms and treatments
ABOUT MALARIA
Malaria is a potentially fatal illness caused by protozoal infection of red blood cells (RBC) with parasites belonging to the genus Plasmodium, transmitted to humans by the bite of a Plasmodium-infected female anopheline mosquito, usually between dusk and dawn. The signs and symptoms of malaria illness are varied, but commonly include fever, headache, back pain, chills, increased sweating, myalgia, nausea, vomiting, diarrhoea, and cough. It is difficult to clinically distinguish malaria from other infections without supporting diagnostic techniques such as microscopic examination of a thick/thin blood smear, rapid diagnostic test strip (RDT) or polymerase chain reaction (PCR).
DIAGNOSIS OF MALARIA
UNCOMPLICATED MALARIA
Malaria initially presents similarly to a minor systemic viral illness, with symptoms such as fever, headache, back pain, chills, increased sweating, myalgia, nausea, vomiting, diarrhoea, and cough. There is no combination of clinical signs or symptoms that reliably distinguishes this initial presentation from other fevers. If treated promptly and effectively, a full recovery is expected.
SEVERE MALARIA
Untreated or poorly treated infections in malaria-naïve patients, especially due to Plasmodium falciparum, can rapidly progress to severe malaria, manifesting with one or more of the following: coma, metabolic acidosis, severe anaemia, hypoglycaemia, acute renal failure, acute respiratory distress syndrome (ARDS), and death in the majority of cases if left untreated. Most severe malaria is due to Plasmodium falciparum, although severe malaria due to Plasmodium vivax, Plasmodium ovale, and Plasmodium Knowlesi has also been recognized (Cullen-2016). Progression from uncomplicated malaria to severe malaria can be rapid (within hours to days) without prompt and effective treatment.
Examples of different presentations of severe malaria can be found in the following table.
Presentations of Severe Falciparum Malaria and Corresponding Criterion
| Presentation | Criterion |
| Impaired consciousness | A Glasgow coma score of < 11 in adults or Blantyre coma score < 3 in children |
| Prostration | Generalized weakness so that the person is unable to sit, stand or walk without assistance |
| Multiple convulsions | More than two episodes within 24 h |
| Acidosis | A base deficit of > 8 mEq/L or, if not available, a plasma bicarbonate level of < 15 mmol/L or venous plasma lactate > 5 mmol/L. Severe acidosis manifests clinically as respiratory distress (rapid, deep, laboured breathing) |
| Hypoglycaemia | Blood or plasma glucose < 2.2 mmol/L (< 40 mg/dL) |
| Severe malarial anaemia | Haemoglobin concentration < 5 g/dL or a haematocrit of < 15% in children < 12 years of age (< 7 g/dL and < 20%, respectively, in adults) with a parasite count > 10,000/μL |
| Renal impairment | Plasma or serum creatinine > 265 μmol/L (3 mg/dL) or blood urea > 20 mmol/L |
| Jaundice | Plasma or serum bilirubin > 50 μmol/L (3 mg/dL) with a parasite count > 100,000/μL |
| Pulmonary oedema | Radiologically confirmed or oxygen saturation < 92% on room air with a respiratory rate > 30/min, often with chest indrawing and crepitations on auscultation |
| Significant bleeding | Including recurrent or prolonged bleeding from the nose, gums, or venepuncture sites; haematemesis or melaena |
| Shock | Compensated shock is defined as capillary refill > 3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure < 70 mm Hg in children or < 80 mmHg in adults, with evidence of impaired perfusion (cool peripheries or prolonged capillary refill) |
| Hyperparasitaemia | P. falciparum parasitaemia > 10% |
Source: WHO Guidelines for Malaria, 13 July 2021.
Severe Plasmodium vivax malaria is defined as for falciparum malaria but with no parasite density thresholds. Severe Plasmodium knowlesi malaria is defined as for falciparum malaria, but with 2 density thresholds: hyperparasitemia >100,000/μL; jaundice, >20,000/μL.
The severity of Plasmodium falciparum is linked to sequestration of infected erythrocytes within the microvasculature of various organs, including the brain. Several mechanisms have been proposed for cerebral malaria including mechanical microvascular obstruction by sequestered infected erythrocytes, activation of immune cells and release of pro-inflammatory cytokines, endothelial dysfunction, dysregulation of coagulation pathways, blood–brain barrier permeability, and brain swelling (Wassmer-2015, Wassmer-2017).
There is no formal WHO definition for complicated malaria (a progression between uncomplicated and severe malaria). Amivas defines complicated malaria as malaria complicated by conditions precluding effective oral treatment, thus making parenteral therapy a clinical consideration. Complicated malaria includes malaria infections not meeting the WHO-2021 criteria for severe malaria but in which the patient may benefit from treatment with an IV antimalarial medication. As examples, this may include patients unable to tolerate oral medications, patients with rapid clinical deterioration, or patients with significant comorbidities (Twomey-2015).
DIAGNOSIS & TREATMENT ALGORITHM
Consideration should be given to official guidance on the appropriate use of antimalarial agents. It is recommended that Artesunate Amivas should be used to treat patients with severe malaria only after consultation with a physician with appropriate experience in the management of malaria.
TREATMENT OF SEVERE MALARIA
National treatment algorithms should be followed.
The WHO provides detailed guidelines in the management and treatment of severe malaria. Based on high-quality evidence, a strong recommendation of intravenous or intramuscular artesunate is prescribed by the WHO for at least 24 hours until oral medication can be tolerated, at which point 3 days of artemisinin-based combination therapy (ACT) (add a single dose of primaquine in areas of low transmission) is recommended to complete the treatment regimen (WHO-2021).
The Artesunate regimen is 2.4 mg/kg given as an intravenous injection at 0, 12 and 24 h then daily thereafter. After completion of a minimum of 24 h therapy a full course of an oral ACT should be taken when the patient can tolerate oral medication. (Lalloo-2016).
DRUG RESISTANCE TESTING OF MALARIA
National guidelines should be followed for monitoring for drug-resistant parasites. After stopping Artesunate Amivas, all patients should receive a complete treatment course of an appropriate oral combination antimalarial regimen. Otherwise, recrudescence of the primary infection may occur that can be mistaken for a drug resistant parasite.
DISCLAIMER
This advice is only intended as a short summary of current clinical guidance and clinical literature for the treatment of severe malaria. The webpage is updated regularly but the medically qualified reviewer should confirm the intended therapeutic intervention according to official National guidance available for their country and follow the approved prescribing information for the products available to the clinician.
REFERENCES
All the cited references are available in full print PDF versions from these links.
Cullen K, Mace KE, Arguin PM. Malaria Surveillance – United States, 2013. MMWR Surveill Summ 2016; 65(2): 1-22. Available from: https://www.cdc.gov/mmwr/volumes/65/ss/ss6502a1.htm
European Centre for Disease Prevention and Control. Malaria. Surveillance report dated 25 July 2019. Available from: https://ecdc.europa.eu/en/publications-data/malaria-annual-epidemiological-report-2017
Lalloo DG, Shingadia D, Bell DJ, Beeching NJ, Whitty CJM, Chiodini PL for the PHE Advisory Committee on Malaria Prevention in UK Travellers. UK malaria treatment guidelines 2016. J Infect 2016; 72(6): 635-649. Available from: https://www.journalofinfection.com/article/S0163-4453(16)00047-5/abstract
Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev 2014; 3(1-115). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532684/
Twomey PS, Smith BL, McDermott C, Marino A, McCarthy W, Kachur P, et al. Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use under an Investigational New Drug Protocol. Ann Intern Med 2015; 163(7): 498-506. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627466/
Wassmer SC, Taylor TE, Rathod PK, Mishra SK, Mohanty S, Arevalo-Herrera M, et al. Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographic Approach. Am J Trop Med Hyg 2015; 93(3 Suppl): 42-56. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574273/
Wassmer SC, Grau GE. Severe malaria: what’s new on the pathogenesis front? Int J Parasitol 2017; 47(2-3): 145-152. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5285481/
World Health Organization. Guidelines for malaria. 13th July 2021. Available from: https://www.who.int/publications/i/item/guidelines-for-malaria