OWSD Nigeria National Chapter Presents: Antimalarial drug resistance highlights women as the most vulnerable group

August 25, 2020

Fourteenth edition of the OWSD Nigeria National Chapter University of Port Harcourt Branch series of scientific communications: Ifeyinwa Chijioke-Nwauche on antimalarial drugs and women

Antimalarial drug resistance highlights women as the most vulnerable group

By

Ifeyinwa Chijioke-Nwauche

Malaria as we all know is caused by 5 species of Plasmodium parasite (P. falciparum, P. ovale, P. vivax, P. malariae and P. knowlesi). Out of all these species, the one that causes more severe and malignant malaria is P. falciparum and it is responsible for about 98% confirmed cases of malaria in Nigeria and is associated with significant morbidity and mortality. The main vector of malaria in Nigeria is female Anopheles gambiae but there are other species of Anopheles.

Vulnerable groups to malaria include pregnant women (especially in first pregnancies), children especially those under five years of age, immunocompromised persons (HIV-positive patients (a greater percentage are women), transplant patients, patients that are undergoing cancer treatment, sickle cell anaemia patients and visitors from non-endemic region).

In as much as malaria is not gender specific apart from the peculiar vulnerability of pregnant women, there are influencing factors to vulnerability in women and these include social, economic, cultural factors and access to preventive and treatment measures. There is marginilization of women due to entrenched inequalities in areas such as education. Women are less informed and have less access to treatment and preventive measures due to their low economic power and dependence on their husbands. This is particularly so in rural areas where there are more economically disadvantaged and low social status women.  All these, in addition to the social pressure of providing meals for the family even when they are ill-disposed and their care-giving responsibility predispose women more to malaria infection.

Malaria is the leading cause of morbidity and mortality in pregnant women in endemic regions such as Africa and Asia. The consequences of malaria in pregnancy include anaemia which causes about 10,000 maternal deaths, low birth weight babies due to intrauterine growth retardation, abortion, premature delivery, stillbirth and maternal death. About 11% of deaths due to malaria in Nigeria have been attributed to malaria. As a result of this, the WHO recommends a treatment measure to prevent malaria in pregnancy termed Intermittent Preventive Treatment for malaria in pregnancy (IPTp). This is the administration of the drug Sulphadoxine-pyrimethamine (SP) to all pregnant women as part of their antenatal care usually starting in the second trimester. Each dose is given one month apart with the aim of taking at least 3 doses before delivery.

It is recommended that malaria be treated after definitive or confirmed diagnosis based on test either using a rapid diagnostic test kit (RDT) or microscopic confirmation of parasites from blood film.

Goals of treatment of malaria

• Provide rapid and long lasting cure
• Reduce morbidity including malaria-related anaemia especially in pregnant women
• Prevent the progression of uncomplicated malaria to severe and potentially fatal diseases
•  Minimize the likelihood and rate of development of drug resistance in addition to reducing transmission

Recommended treatment for malaria according to the World Health Organization is the use Artemisinin Combination therapy (ACT), which involves the use of drugs containing an artemisinin-based drug with a partner drug with another mechanism of action so as to ensure the complete killing of the parasite in the blood stream. Some of the partner drugs include: lumefantrine, amodiaquine, piperaquine, mefloquine etc.

However, sometimes the desired treatment goal is not always achieved as a result of treatment failure. Many factors have been associated with treatment failure and this discussion is focused on drug resistance as a major cause of treatment failure.

The World Health Organization defines antimalarial drug resistance as ‘The ability of a parasite strain to survive and multiply despite the proper administration and absorption of an antimalarial drug in the doses equal to or higher than usually recommended, provided drug exposure is adequate’.                                          

Causes of antimalarial drug resistance:

• Increased drug pressure: self-medication, wrong diagnosis, fake or substandard drugs, suboptimal dose, inappropriate use of drugs
• Artemisinin monotherapy
• Host factors: age, reduced immunity
• Spontaneous mutations in the parasite gene
• Mobile populations and migrants
• High treatment costs

Resistance and Immune status of the patient

• Reduced immunity as seen in individuals with lower immunity (pregnant women, children, HIV-patients) allows the survival of residuum of parasites thereby potentially increasing the development, intensification and spread of resistance. 

• Delayed cure rate and higher rate of recrudescence as obtained in HIV-persons accelerate the spread of resistant parasites.

Public Health and clinical consequences of antimalarial drug resistance

• Increase in malaria transmission                                   
• Frequency in severe illness especially in vulnerable groups                                               
• Increased mortality rates
• Increased treatment costs 

Clinical consequences

• Increased treatment failure
• Reduced treatment efficacy
• Delayed initial therapeutic response
• Complications: anaemia, organ involvement, hypoglycemia, complications during pregnancy etc.

Dealing with resistance

To prevent or slow down onset of resistance, the following should be done

• Use of drug combinations with different mechanisms of action (WHO recommends ACT drugs)
• Strict adherence to the dosage regimens as recommended by the manufacturers of the drugs
• The T3 (test, treat and track) principle of WHO. This implies testing to confirm parasite presence, treating with the right drug and tracking the patient for review.

The Gender connection

• Pregnant women (Malaria parasites from the pregnant women have been found to exhibit higher resistance).
• Need for adherence to WHO recommendation of IPTp in malaria endemic areas. Recommended drug is Sulphadoxine-Pyrimethamine
• Care givers (90% of care givers are women, usually for their children, husbands, grandchildren etc.)
• Health-seeking behaviour: women tend to seek health services more than men
• Women are also known to adhere to medications more than men
• Home keepers and managers

Advice to women

• As home managers, ensure clean environment, disposal of mosquito breeding cans around the home
• Ensure your family sleeps under insecticide treated nets
• Use window and door nets in the homes
• Avoid patronising unregistered drug outlets to avoid fake and substandard drugs
• Consult professionals (your pharmacist or physician) before use or giving any drug to your family
• Pregnant women should endeavour to have good antenatal care and ensure they take IPTp
• Use drugs appropriately and in correct doses
• Confirm diagnosis of malaria before treatment

References

WHO. Guidelines for the treatment of Malaria, Third Edition, 2015

Greenwood BM. & Armstrong JR. Comparison of two simple methods for

determining malaria parasite density. Trans R Soc Trop Med Hyg, 1991; 85, 186-8.

Menendez C, Bardaji A, Sigauque B, Sanz S, Aponte J.J, Mabunda, S. & Alonso PL.

Malaria prevention with IPTp during pregnancy reduces neonatal mortality. PLoS One, 2010;

5, e9438.

National Population Commission & National Malaria Control Programme (NPC& NMC). 2012. Nigeria Malaria Indicator Survey, 2010 Final Report, Federal Republic of Nigeria.

Owoyemi AJ, Ladi-Akinyemi. Health-seeking behaviour for infants by caregivers in semi-urban area of Lagos State, Nigeria. 2017, Vol.17, Issue 1; pp 14-19.

UNDP Discussion Paper: Gender and Malaria, December 2015

About the author

Ifeyinwa Chijioke-Nwauche (BPharm, PhD, PharmD) is a Clinical Pharmacist and a Senior Lecturer in the Department of Clinical Pharmacy and Management, Faculty of Pharmaceutical Sciences, University of Port Harcourt, Nigeria.

Email: ifeyinwa.chijioke-nwauche@uniport.edu.ng

Phone: +2348080509050

LinkedIn handle: https://www.linkedin.com/in/ifeyinwa-chijioke-nwauche-5180211b5/