“This situation will always remain dynamic”: an interview with Dr Dorothy Achu

As part of the launch of an antimalarial drug resistance strategy for Africa, we spoke with Dr Dorothy Achu, WHO’s new Team Lead for Tropical and Vector Borne Diseases in the Regional Office for Africa. Previously, Dr Achu served as Permanent Secretary for Cameroon’s National Malaria Control Programme in the Ministry of Public Health. This conversation has been edited for concision and clarity.

First, can you give us a sense of the scope of the problem? Why is antimalarial drug resistance in Africa important to deal with now?

To begin with, sub-Saharan Africa holds the greatest burden of malaria, globally: approximately 95% of cases and deaths. And that's huge. So the problem of malaria in Africa itself is very important. Compounding this dilemma, Africa has in the very recent past been faced with resistance to a series of drugs, including antimalarial drug resistance.

We don’t have that many options for malaria drugs. As it stands, we just have artemisinin-based combination therapies (ACTs) for uncomplicated malaria. So, any threat to these drugs will really be devastating to the epidemiology of the continent and could lead to lots and lots of cases and deaths, which we obviously want to avoid.

Since 2015–16, malaria cases have already been on the increase in many African countries. So, the drug resistance we’re seeing is an additional threat that we must manage, even as we are trying to move in a more positive direction and return to the progress we saw against malaria before 2015.

Antimalarial drug resistance was also a problem in Africa in the 1970s and 1980s. How is the situation different now, and what can we learn from that earlier experience?

The drug resistance today is a bit different because we are using better drugs – we are using combination therapies that are more expensive and more efficacious. In the 70s and 80s, we were using mostly monotherapies – one drug at a time – such as chloroquine. Resistance to chloroquine spread through Africa. Many countries changed to SP [sulfadoxine–pyrimethamine] instead, and, because the situation is always dynamic, resistance to SP quickly emerged as well.

In the past, it took quite a while – about 2 decades – for resistance to be clinically observed. What really drove and accelerated this resistance was the presumptive diagnosis and treatment of cases, meaning cases that were diagnosed and treated based only on clinical symptoms, without a proper diagnosis. So, many patients who may not have needed these drugs were taking them. Secondly, most of these drugs were also being used for prevention. Pregnant women and even children used to receive weekly doses of chloroquine. This caused a lot of pressure on the malaria parasites, and they eventually developed resistance to these drugs.

Today, we have better drugs – ACTs, which combine 2 effective drugs – but there is still a risk of developing drug resistance. It is very important to recognize that, when the efficacy of one of the drug’s 2 components is weakened by resistance, the second component is also affected. That second drug will become exposed, and thus the parasite is more likely to develop resistance against it as well. So what today is an effective drug combination for treating malaria could quickly become ineffective if resistance is allowed to grow.

So, what can we learn from this? First, the combination therapies we have today – especially ACTs – should be used in a very rational manner. We need to preserve their efficacy by using them to treat only the cases that really need them. The good news is we now have effective diagnostics and tests introduced in the last 2 decades that can rapidly identify the patients that are really suffering from malaria and require ACTs for treatment. Second, we are trying to avoid the use of first-line ACTs for prevention purposes. Because they are given to large populations of people who don’t necessarily need them, that increases the likelihood of developing resistance.

And third, we need to continue to find even better ways of carrying out surveillance of resistance’s spread. As I said, drug resistance is a very dynamic process – it’s never going to end and we’re going to have face this issue over and over again. So we need to strengthen surveillance of drug efficacy and employ new tools to do it smarter, like genotyping and molecular methods, across our health systems.

South-East Asia is also seeing growing resistance to both components of ACT therapy – artemisinin and various partner drugs. What can the South-East Asian experience tell us about resistance in the African context?

Well, South-East Asia has a different kind of setting in terms of the parasites transmitting malaria. What we noticed there is the prevalence of the Plasmodium falciparum parasite rapidly decreased despite the resistance that was described. So, it shows that, if the drugs are used properly – alternating one after the other – and if the drugs that are showing resistance based on efficacy studies are replaced with more effective ones, you can still bring down the parasite prevalence. The faster you can reduce that prevalence, the better off you’ll be, because you have fewer cases to deal with and less pressure on parasites for resistance to develop.

In Africa, we can follow that same strategy in places where prevalence levels are going down. But we also have very high burden countries where the decrease in prevalence is very slow, because of the variability of the parasites. It will be important in those areas to anticipate the problem by diversifying the use of ACTs – not using just one type of ACT for large populations – to make sure that we don’t create the conditions for resistance to flourish. We have seen in certain areas that multiple first-line therapies can help reduce the pressure on the parasites to mutate and develop resistance. This can also help bring down prevalence, especially over the long term.

A lot of work also needs to be done in Africa to ensure the availability of quality-assured drugs. At the moment, we very seldomly have our own drug manufacturing sites, and when we don't have a homegrown market supply of quality-assured drugs, supplies can become very inconsistent and the population gets exposed to substandard treatments; this, in turn, can trigger resistance because the drugs do not confer complete clearance of the parasites. Instead, they leave some parasites circulating, and those can easily develop mutations. So, our goal must be to strengthen the availability of quality drugs, fight against illicit sales of bad drugs, and improve communication so that people know the dangers of practices that will accelerate resistance.

What else should we be doing to slow or stop anti-malarial drug resistance in Africa?

I already mentioned the importance of increasing surveillance. There's a lot of data we do not have so we don’t even know how severe the problem is. If Rwanda and Uganda are registering high rates of resistance, it’s because they have good surveillance systems already in place. In Cameroon, for example, where I've worked for almost all my life, some research teams have already started seeing a decrease in parasite clearance time for ACTs in certain sites. So even in Central Africa, we know that if we increase surveillance, we are going to pick up more signs of growing resistance.

So how do we solve the problem? We increase surveillance, and we make sure that once there is resistance, we rapidly change the drug we’re using. We also need to think ahead about what the new drugs and options can be. We shouldn't wait until we have full-blown resistance before we start replacing them. So, we are looking forward and working with R&D partners on finding new drugs and exploring new ways of combining old drugs to make them more effective.

I would also stress that we need strong regulatory environments. If we choose treatment guidelines and protocols that are better for certain communities, depending on their drug efficacy profiles, then we should enforce those policies. Sometimes good policies are made but never implemented. We need regulation that ensures good quality products, good quality care, and health facilities; enforces guidelines; and helps everyone be aware of the dangers of using substandard drugs and the impact that has on resistance.

Should people be worried that ACTs are going to stop working?

People should be quite worried, because we know that ACTs are the only drugs we have for uncomplicated malaria. So, if we do not have any other option, then what happens to our children when they are sick? We will have to give them drugs that are not effective, and they will be ill for longer periods. We will have many more severe malaria cases and those will lead to more deaths.

When we had chloroquine resistance, there were hundreds of thousands more deaths because children fell sick, couldn't get treatment in time, the malaria grew severe, and many of them died. If that situation repeats, we may see an increase in mortality and in the number of days children must stay in the hospital. This should worry communities.

Even if another treatment does get developed, it may be costly, so many vulnerable children and families may not be able to afford these new and effective drugs. All of this should get us thinking about how we can delay this problem of resistance as much as possible. We should also work to get new, affordable treatment options on the market before ACT resistance becomes full-blown.

Is there anything else you want to add?

I want to repeat something I said earlier, which is this situation will always remain dynamic. Parasites will evolve and mutate, and resistance will continue to be an issue because we have large populations taking treatments. So we need to be constantly thinking about how to stay a few steps ahead, and we have to help communities be disciplined about using effective treatments. Because it’s only in ensuring this discipline, and making good policies in good time, that we are going to prevent the worst consequences of antimalarial drug resistance.