A large proportion of malaria patients in endemic countries in Africa are likely to receive doses of malaria medicine that are too low to offer effective treatment, according to new research presented at the 7th Multilateral Initiative on Malaria (MIM) Pan African Malaria Conference taking place in Dakar this week. Researchers found that an estimated 21.3 million people--or 24 percent of all confirmed malaria cases--were at risk of being prescribed inadequate doses of artemisinin-based combination therapy (ACTs), the frontline treatment against Plasmodium falciparum malaria.
Researchers from the Worldwide Antimalarial Resistance Network (WWARN) used modeling to identify populations of vulnerable patients that are at risk of receiving sub-optimal dosing of ACTs for the treatment of P. falciparum malaria in Africa. The research team reviewed publicly available data from 40 endemic countries where a total of 89.6 million cases of malaria were reported in 2015. The results found that patient groups at risk included malnourished children under five years of age, overweight and obese adults, pregnant women, patients with uncomplicated hyperparasitemia and patients using poor quality medicines.
"Antimalarial drugs remain a key tool for the control and elimination of malaria. These findings are worrying given that sub-optimal dosing among vulnerable populations not only leads to poorer treatment outcomes for patients, but can also fuel the emergence and spread of antimalarial drug resistance," said Dr. Kasia Stepniewska, head of statistics at WWARN and lead researcher on the study. "There is an urgent need to tailor therapeutic approaches for populations at risk in order to protect the efficacy of drugs and prevent the development of drug resistance."
Vulnerable groups such as malnourished children, pregnant women, overweight and obese adults and patients with underlying infections such as HIV respond differently to antimalarial drugs than the general population, who are usually the ones studied when dosage regimens are developed. As a result, vulnerable groups may require different treatments or dosage regimens, which are in some cases unavailable or difficult to implement and, in other cases, are not being followed by healthcare workers.
In isolation, each of these groups is a small part of the population, but added together, their sum covers a substantial part of the malaria-affected population in sub-Saharan Africa.
If malaria treatments are not strong enough to eliminate the malaria parasites in a patient, the remaining parasites that withstood the low dose could evolve to become more resistant to future treatment. In addition, poor quality antimalarials are common in many endemic countries and contribute to the sub-therapeutic intake of drugs. The exposure to sub-optimal dosage, combined with other factors such as the use of sub-standard medicines and partial adherence, are contributors to drug resistance emerging and spreading. The WWARN Antimalarial Quality Surveyor, an online mapping tool, demonstrates the scale of drug quality issues worldwide.
Resistance to antimalarial medicines has long been recognized as a serious threat to global efforts to control and eliminate malaria. Protecting the efficacy of malaria treatments is a top priority for the malaria community in sub-Saharan Africa. To date the epicenter of artemisinin drug resistance is Southeast Asia, namely Cambodia, the Lao People's Democratic Republic, Myanmar, Thailand and Viet Nam. By using collaborative approaches to analyze data across many countries, researchers hope to develop strategies that will prevent or at least delay the spread or emergence of drug resistance in Africa.
"While artemisinin resistance has not yet been confirmed in Africa, we can do a lot more to improve how we use antimalarials and so reduce the risk of artemisinin and partner drug resistance becoming established here," said Karen Barnes, professor of clinical pharmacology at the University of Cape Town, South Africa and head of pharmacology at WWARN.
On a smaller-scale, results from an analysis of 140 prescription records from public and private health centers in southeast Nigeria were presented at MIM by Dr. Okeke Chinyere of the University of Nigeria. The research found antimalarial drugs to be prescribed in wrong doses in 25 percent of cases in public facilities and almost 40 percent of cases in private facilities. More injections (87.7 vs 45.6 percent) and more antibiotics (64.3 vs 23.4 percent) were prescribed in private than public health facilities
Chinyere suggests this high use in private facilities may be explained by the fact that "some patients would ask for injections even when this has not been prescribed" combined with possible profit-oriented motives of providers or from prescriber belief that "patients expect and are satisfied by receiving injections."
Improper use of medicines is not a problem that is unique to malaria; the World Health Organization estimates that more than half of all medicines are inappropriately prescribed, dispensed or sold. The problem is especially acute in developing countries where it is compounded by health system weaknesses such as heavy patient load, lack of enforced regulations, pressure of promotional activities, and lack of supervision, monitoring and evaluation.
Another study presented at the conference, which looked at 21 public outpatient facilities in Uganda, found over-prescription to be prevalent. Despite improvements in diagnostic tests, Dr. James Apollo Kapisi and colleagues from the Infectious Diseases Research Collaboration found that prescription of ACTs to patients with negative malaria test results was common at Malaria Reference Centers. Among those with a negative malaria test result, patients with a negative rapid diagnostic test were more likely to be prescribed antimalarials compared to those with a negative microscopy result.
Similarly, in another study across five hospitals in Western Kenya being presented at MIM by Beatrice Amboko with the KEMRI-Wellcome Trust Research Programme, researchers found that there were high rates of malaria treatment given to children who tested negative for malaria and likely over-use of injectable antimalarial drugs. Almost half of the clinical malaria cases prescribed parenteral antimalarials had no signs of severe malaria documented.
"We must ensure that people are getting appropriate treatment for malaria at the correct dosage," said professor Oumar Gaye, local organizing committee chair for the MIM Pan African Malaria Conference. "We are identifying some of the challenges that need to be overcome to ensure that medical prescribers and patients are all working in the best interest of the patient and thinking about conserving our best antimalarial drugs against potential drug resistance in Africa."