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 Table of Contents  
COMMENTARY
Year : 2021  |  Volume : 26  |  Issue : 2  |  Page : 122-123

Treatment failure in malaria: Causes and complexities


Department of Epidemiology and Environmental Biology, National Institute of Malaria Research, New Delhi, India

Date of Submission03-Nov-2021
Date of Acceptance24-Dec-2021
Date of Web Publication10-Feb-2022

Correspondence Address:
Dr. Arvind Nath
National Institute of Malaria Research, Sector 8, Dwarka, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmgims.jmgims_94_21

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  Abstract 


Treatment failure in malaria is a major dilemma that health-care workers face throughout the country. True drug resistance is one of the causes after ruling out compliance and drug quality issues; the other causes being re-infection with a new strain of the parasite during the treatment period or, in the case of Plasmodium vivax, the release of hypnozoites from the liver. Since it is difficult, in the field, to identify the cause as being due to re-infection with a new strain of the parasite during the treatment period or, in the case of P. vivax, the release of hypnozoites from the liver, providing antimalarials to overcome drug resistance is the mainstay of therapy.

Keywords: Drug resistance, hypnozoite, malaria


How to cite this article:
Nath A. Treatment failure in malaria: Causes and complexities. J Mahatma Gandhi Inst Med Sci 2021;26:122-3

How to cite this URL:
Nath A. Treatment failure in malaria: Causes and complexities. J Mahatma Gandhi Inst Med Sci [serial online] 2021 [cited 2022 May 24];26:122-3. Available from: https://www.jmgims.co.in/text.asp?2021/26/2/122/337440




  Introduction Top


The treatment of malaria depends on the species of Plasmodium parasite causing it.[1] If the diagnosis is Plasmodium vivax, the patient is treated with chloroquine and primaquine. If it is Plasmodium falciparum, treatment is by way of artemisinin-based combination therapy (ACT) and primaquine. Mixed infections are treated by ACT and primaquine. A dilemma that the health worker faces is what should be done if a patient, despite full compliance with treatment and no history of vomiting or diarrhea, does not respond parasitologically. If it is a case of P. falciparum malaria, this treatment failure could be either due to true drug resistance or due to re-infection with a new strain of P. falciparum during the treatment period.[2] If it is a case of P. vivax malaria, the treatment failure could be due to either true drug resistance, due to re-infection with a new strain of P. vivax during the treatment period, or due to the release of hypnozoites from the liver. In the field, it is difficult for health-care providers to differentiate between all these possibilities. The aim of this paper is to provide a practical solution as to what he/she can do when faced with such a dilemma.


  National Strategy Top


The Government of India, in 2016, adopted the National Framework for Malaria Elimination in India 2016–2030.[3] This was based on WHO's Global Technical Strategy for malaria, covering the same period, which was adopted in 2015 and updated in 2021.[4]

The aim is to reach no malaria cases by 2027 and then wait for 3 years before certification of malaria-free status can be granted by the WHO. It is already the end of 2021 and India is about to reach the halfway mark of this period from 2016 to 2027. The Annual Parasite Incidence (API) has also come down significantly (it was 0.32 during 2018[5]).


  Current Therapy Strategies Top


At present, the treatment of malaria due to P. vivax is carried out by the administration of 3-day treatment with chloroquine and 14-day treatment with primaquine. The role of primaquine is to kill the hypnozoites.

The therapy of malaria due to P. falciparum is dependent on the patient's residence. If the patient resides in any part of the country, except the eight north-eastern states, he/she is treated with an ACT consisting of 3-day treatment with artesunate and 1-day treatment with sulfadoxine-pyrimethamine along with 1-day treatment with primaquine. The role of primaquine is to kill the gametocytes. If the patient resides in any of the eight north-eastern states, he/she is treated with a combination of artemether and lumefantrine for 3 days because drug resistance to sulfadoxine-pyrimethamine had been observed in these eight north-eastern states, and hence, lumefantrine was chosen to replace sulfadoxine-pyrimethamine in these areas.[6]

As the API continues to decrease, it is likely that those malaria cases which will continue to persist in the community would be the drug-resistant cases of malaria. In the National Drug Policy on Malaria 2013, it is mentioned that resistance should be suspected if, despite full treatment and no vomiting or diarrhoea, the patient does not respond clinically and parasitologically within 3 days. In such cases, it is advised to give oral quinine with tetracycline or doxycycline.[6]


  Alternative Strategies Top


A problem that would occur is if the drug-resistant malaria patient is a child because tetracycline and doxycycline are contraindicated in this age group. However, the artemether–lumefantrine combination which is suitable for children has been found to be effective in the treatment of malaria caused by chloroquine-resistant P. vivax.[7]

Similarly, since artemisinin- and lumefantrine-resistance have not been documented in India, the artemether–lumefantrine combination would also be effective in the treatment of malaria caused by sulfadoxine-pyrimethamine-resistant P. falciparum.

Artemether–lumefantrine is to be prescribed as per body weight:

  • 5–14 kg 20 mg artemether plus lumefantrine 120 mg
  • 15–24 kg 40 mg artemether plus lumefantrine 240 mg
  • 25–34 kg 60 mg artemether plus lumefantrine 360 mg
  • 35 kg and above 80 mg artemether plus lumefantrine 480 mg.


Artemether–lumefantrine is not to be given to children weighing less than 5 kg.

These are available as artemether 20 mg plus 120 mg lumefantrine, as well as 40 mg artemether plus 240 mg lumefantrine dispersible tablets for children. For adults, artemether 80 mg plus 480 mg lumefantrine tablets/capsules are available.

A total of 6 doses have to be administered: the first dose at the time of diagnosis; second dose after a gap of 8 h; third dose after 24 h; fourth dose after 36 h; fifth dose after 48 h; and sixth dose after 60 h.

Primaquine resistance has not yet been documented in India. Therefore, in the case of malaria caused by drug-resistant P. vivax, it is important to give the 14-day regimen of primaquine at a dose of 0.25 mg/kg body weight daily.

Similarly, in the case of malaria caused by drug-resistant P. falciparum, it is important to give primaquine at a dose of 0.75 mg/kg body weight on day 2 of therapy. Primaquine is not to be given to children less than 1 year of age.

Acknowledgments

I thank Dr. George M. Varghese, Professor and Head, Department of Infectious Diseases, Christian Medical College and Hospital, Vellore, India, for his valuable inputs in the write-up. I also thank Dr. Puneet Kumar, Child Specialist, and Member, Indian Medical Association, Dwarka Branch, New Delhi, India, for his valuable inputs during the preparation of this document.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Government of India. Guidelines for Diagnosis and Treatment of Malaria in India 2011; 2011. Available from: https://nvbdcp.gov.in/WriteReadData/l892s/Guidelines%20for%20Diagnosis2011.pdf. [Last accessed on 2021 Oct 07].  Back to cited text no. 1
    
2.
Medicines for Malaria Venture & World Health Organization. Methods and Techniques for Clinical Trials on Antimalarial drug Efficacy: Genotyping to Identify Parasite Populations: Informal Consultation Organized by the Medicines for Malaria Venture and Cosponsored by the World Health Organization, 29-31 May, 2007. Amsterdam, The Netherlands: World Health Organization; 2008. Available from: https://apps.who.int/iris/handle/10665/43824. [Last accessed on 2021 Sep 27].  Back to cited text no. 2
    
3.
Government of India. National Framework for Malaria Elimination in India 2016-2030. Available from: https://nvbdcp.gov.in/WriteReadData/l892s/National-framework-for-malaria-elimination-in-India-2016%E2%80%932030.pdf. [Last accessed on 2016 Feb 11].  Back to cited text no. 3
    
4.
World Health Organization. Global Technical Strategy for Malaria 2016-2030. Available from: https://www.who.int/publications/i/item/9789240031357. [Last accessed on 2021 Sep 17].  Back to cited text no. 4
    
5.
Government of India. Annual Report of National Vector-Borne Disease Control Programme 2018. Available from: https://nvbdcp.gov.in/Doc/Annual-Report-2018.pdf. [Last accessed on 2021 Aug 25].  Back to cited text no. 5
    
6.
Government of India. National Drug Policy on Malaria 2013. Available from: https://nvbdcp.gov.in/WriteReadData/l892s/National-Drug-Policy-2013.pdf. [Last accessed on 2021 Sep 14].  Back to cited text no. 6
    
7.
Bassat Q. The use of artemether-lumefantrine for the treatment of uncomplicated Plasmodium vivax malaria. PLoS Negl Trop Dis 2011;5:e1325. Epub 2011 Dec 27. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246442/. [Last accessed on 2021 Oct 07].  Back to cited text no. 7
    




 

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