Hope dims on ending malaria by 2030 as disease becomes ‘untreatable’, mosquitoes ‘uncontrollable’

Nigeria is sitting on a ticking time bomb as resistance to recommended malaria drugs and mosquito insecticide has reached Africa. Although the National Malaria Elimination Programme (NMEP) says the phenomenon has not been reported in the country, scientists have warned there will be a catastrophic spike in infections and deaths in the region if nothing is done urgently. They warn that the global goal of eliminating malaria by 2030 looks increasingly under threat because resistance is emerging across the continent and it is only a matter of time before it gets to Nigeria, CHUKWUMA MUANYA writes.

Contrary to warnings by scientists on the need for urgent action to stop the spread of drug-resistant malaria, ‘untreatable’ disease, and uncontrollable mosquitoes, the National Malaria Elimination Programme (NMEP) has said Nigeria has not recorded treatment failure with the drug-of-choice, Artemisinin-based Combination Therapies (ACTs), but delayed parasite clearance.

The NMEP, however, said Nigeria has reported resistance of mosquitoes to recommended insecticides but it is currently addressing the situation.

Scientists, led by the World Health Organisation (WHO), had warned that a malaria-carrying mosquito species that thrives in urban areas and resists all insecticides was causing outbreaks in places that had rarely faced the disease.

Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. It is preventable and curable.

Malaria causes high fevers, bone-shaking chills, fierce headaches and vomiting. Without treatment, it can be fatal. It hits small children hardest: They make up most of the 620,000 malaria deaths each year. If a mosquito feeds on a person who already has the parasite, the insect ingests it along with the person’s blood, and the parasite begins a new life cycle in the mosquito’s body. About a week later, if that mosquito bites someone new, it passes on the parasite with its saliva.

While malaria vaccines now exist and are most effective at saving lives when used in conjunction with effective anti-malarial treatments, stakeholders are worried because Nigeria has the highest burden of malaria globally despite efforts by the Federal Government and partners to change the narrative.

According to the 2023 World Malaria Reports from the WHO, Nigeria is responsible for 31 per cent of the 608,000 global deaths and 27 per cent of 233 million global cases in 2022.

As at 2021, the country accounted for 30 per cent of the global burden, with an estimated 68 million cases and 194,000 deaths yearly. It is estimated that over one thousand children die every day from malaria in Africa.

There are concerns about this because resistance levels have soared in some areas from less than one per cent to more than 20 per cent of cases in the space of three years. The last time resistance to anti-malaria spiked in the continent, it led to a tripling in the number of children dying.

Twenty-eight leading malaria scientists from 10 countries, in a paper published last week in the journal Science, warned that millions of lives could be put at risk unless urgent action was taken to curb the spread of drug-resistant malaria in Africa.

The paper said parasite causing malaria is showing signs of resistance to artemisinin, the main drug used to fight the disease in East Africa.

According to the report, “mutations indicating artemisinin-resistance have been found in more than 10 per cent of malaria infected individuals in Ethiopia, Eritrea, Rwanda, Uganda and Tanzania.”

ACTs have been the cornerstone of malaria treatment in recent years — but there are worrying signs that they are becoming less effective, says the report’s co-author, Lorenz von Seidlein of the Mahidol Oxford Tropical Medicine Research Unit in Bangkok.

“We have increasing reports from East Africa saying that they have documented resistance against the first line treatments against malaria,” he said. “The first line treatments are artemisinin combination therapy — that has been used for the last 20 years and has worked excellently well. And it’s now not working quite as well as it used to do.”

According to another study published in Nature Medicine, artemisinin-based combination therapy has been critical for treating malaria infections caused by the parasite Plasmodium falciparum, with intravenous artesunate an important treatment for severe malaria. Several countries in Eastern Africa, including Eritrea, Rwanda, Tanzania and Uganda, have reported artemisinin partial resistance (ART-R), which puts these lifesaving malaria treatments in jeopardy.

Scientists from the London School of Hygiene and Tropical Medicine as well as institutions in Cameroon, Ethiopia, Tanzania, Mali, Namibia, Uganda and South Africa have issued an urgent call for action in Nature Medicine.

They said artemisinin resistance, primarily mediated by mutations in the P. falciparum Kelch13 (K13) protein, causes delayed parasite clearance. This is a problem, because if the parasite fails to clear from the bloodstream within two days, it can lead to treatment failure and drive drug resistance even further.

According to the researchers, in Africa, mutations associated with ART-R have been confirmed in multiple countries, indicating diverse origins of resistant parasites and emphasising the need for comprehensive containment and control measures.

A similar story has happened before. The parasite became resistant to a previous drug — chloroquine — in East Africa in the 1970s, and resistance reached the west coast by the 1980s. Malaria deaths on the continent trebled from about 493,000 in 1980 to 1.6 million by 2004, according to the study published in Science.

Speaking on spreads of drug resistance malaria to Nigeria, the National Coordinator, NMEP, Dr. Godwin Ntadom, told The Guardian: “The answer is no. As a matter of fact, we have not experienced resistance to the recommended Artemisinin-based Combination Treatments that are currently deployed for the treatment of uncomplicated malaria in Nigeria, and by extension, Africa.

“What has been reported so far is delayed parasite clearance. What does delayed parasite clearance mean? If it took three hours to clear X number of parasites some years ago, it now requires four; five or more hours to clear the same X number of parasites. However, some resistant mutant genes, which could lead to resistance, have been detected in areas such as Rwanda, Uganda and Tanzania, but it is also important to know that the detection of mutant genes in certain areas does not automatically translate to resistance. Unfortunately, each time you hear people talk about ‘Resistance’ you can clearly understand that what they mean is treatment failure.”

Ntadom said one could only talk about resistance following a comprehensive drug efficacy study using appropriate protocol and following up a set of patients or subjects for not less than 28 days, and in some cases, up to 42 or 63 days, depending on the drug being tested.

He, however, pointed out that treatment failure is when a patient fails to recover from malaria illness following the use of anti-malarial medicine.

“Several factors may contribute to this; the commonest here is when a sick individual uses suboptimal dosage of anti-malarial medicine or the anti-malaria is not the recommended ACTs, or the ACTs is of low quality. It could also be as a result of issues relating to pharmacology and pharmacokinetics of the medicines,” Ntadom revealed.

He further explained: “We have also noticed that some individuals shouting of resistance never had malaria in the first instance. If you are sick of other diseases and wrongly diagnosed as malaria, anti-malarial medicines, no matter how potent, will not work for you. So, always obtain a proper diagnosis, especially with the use of malaria rapid diagnostic test when you are not sure of the laboratory. All fevers are not malaria.”

Ntadom, however, said the national programme had recorded some resistance to pyrethroid treated nets and has swiftly introduced new insecticides, which are more potent against the mosquito vectors.

A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums. Pyrethroids are used as commercial and household insecticides. In household concentrations, pyrethroids are generally harmless to humans.

In addition, he said, the country would be introducing biolarvicides for the control of immature vectors of malaria.

Biolarviciding, which is the regular application of biological insecticides to waterbodies, has been observed to be effective in controlling malaria mosquito populations, and is considered safe for humans with limited adverse environmental impact.

On the implications of the parasite and the vector developing resistance to available treatment and prevention tools, Ntadom said: “That is not the situation in Nigeria; so, we have nothing to worry about.”

What is the solution? Is herbal/traditional medicine an option?

Ntadom responded that herbal products also have their places in malaria treatment as well as vector control. He said Artemisinin products are extracted from Artemisia annua plant in China, Quinine from the back of Chinchona tree and Peruvian plants, and Pyrethroid are obtained from Japanese plants.

“This is a challenge to our herbal scientists and researchers to do more. For now, all the programmatically deployed anti-malaria medicines are working optimally,” he said.

Also, recent studies have shown that children with acute malnutrition across Africa and Asia have a higher risk of treatment failure and malaria re-infection, even after being given the best currently available and recommended malaria treatment.

Researchers from the Infectious Diseases Data Observatory (IDDO) at Oxford University analysed data from over 11,000 young children for this study published in Lancet Global Health.

The analysis found that children younger than age five who were very underweight for their height had nearly double the risk of malaria treatment failing, even when given WHO recommended doses of an artemisinin-based combination therapy, which is currently the best treatment for falciparum malaria.

The results from the research study suggest that acute malnutrition in children may play a role not only in treatment failure, but also puts this vulnerable group at higher risk of severe malaria and death.

Meanwhile, before artemisinin therapies were developed, chloroquine was the medicine most used to treat malaria. The authors of the report said in the 1990s and early 2000s, signs that the malaria parasite was developing resistance to chloroquine were widely ignored.

“When chloroquine resistance slowly sneaked into Africa, there was a whole wave of childhood mortality following it. So really, a large number of children — probably in their millions — died because chloroquine didn’t work as well as it used to do. And now we see these first signs that something similar is happening with the ACTs. And that is of course very worrying,” von Seidlein said.

The authors urged policymakers and global funding bodies to act now to prevent artemisinin resistance taking hold. Their recommendations include combining artemisinin drugs with other medicines.

“Combining an artemisinin derivative drug with two partner drugs in triple artemisinin combination therapies (TACTs) is the simplest, most affordable, readily implementable, and sustainable approach to counter artemisinin resistance,” the report said.

The authors also called for the rollout of new, more effective insecticides and mosquito nets, better training of community health workers, the rapid deployment of new malaria vaccines and better monitoring of parasite mutations.

Many of these methods were used to halt the spread of artemisinin resistance in Southeast Asia since 2014, noted von Seidlein.

Muhammad Ali Pate

“Ultimately, there was an understanding that this could be a major health emergency globally and so there were a lot of investments from funders from the high-income countries towards these countries in the Greater Mekong sub-region to stop the spread of artemisinin resistant parasites,” he said.

The report says that a sense of urgency must now be applied to tackling artemisinin resistance in Africa.

“We ask funders, specifically the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and the United States (U.S) Government’s President’s Malaria Initiative, to be visionary and to step up funding for malaria control and elimination programmes to contain the spread of artemisinin resistance in Africa — as they have done effectively in Southeast Asia since 2014,” said the report’s co-author, Ntuli Kapologwe, the director of preventive services at Tanzania’s Ministry of Health.

Reacting to reports suggesting that the alarm on malaria resistance to drug-of-choice is a conspiracy by Western nations to create a market for the new malaria vaccines, Ntadom said: “Development of vaccines against malaria parasites was achieved after trying for over 60 years. This should be a thing of celebration, rather than all these talks. Developing a vaccine against a parasite is a monumental achievement, and this time around, against a disease that has killed millions of children, pregnant women and others across the world for centuries should call for celebration. The malaria vaccine is an additional tool to the already existing set of armamentaria against malaria. It has not come to replace any.”

On whether Nigeria can still eliminate malaria by 2030, Ntadom said: “We are not calling for malaria elimination in 2030. What we are saying is that no one should die of malaria by 2030, and this is very possible. You are aware that the Coordinating Minister for Health and Social Welfare and the Minister of State for Health and Social Welfare recently had a meeting on ‘Rethinking Malaria Elimination in Nigeria’. The idea is to approach the elimination of malaria in a more pragmatic way; to rapidly scale up interventions. The resultant effect of this would be to achieve significant reduction in prevalence as well as crashing to zero, the mortality due to malaria. This is very important in the light of the fact that malaria still contributes between 25 per cent – 30 per cent mortality in under-five years old children.”

While recognising that countries are operating with constrained resources and emerging threats, including resistance to medicines and insecticides, and the evolving impact of climate change, WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, in his remarks during a recent stakeholders’ engagement on rethinking malaria in Nigeria, said: “We need a data-driven approach to identify the most effective and most equitable use of resources to accelerate progress in Nigeria, and other high-burden countries. That means better financing, and better partnerships.”

Ghebreyesus added: “Nigeria has had a long battle with malaria, and while you have made good progress, it remains a major burden of disease, accounting for more than half of hospital visits.

“Nigeria has the world’s largest burden of malaria, with more than a quarter of the world’s cases, and one third of global deaths, most of them children and pregnant women. It is time to turn the tide on this ancient killer. Just a few weeks ago, ministers from high burden countries in Africa met in Cameroon and signed the Yaoundé Declaration, committing to reduce deaths from malaria.

“Now, just two months later, Nigeria is first out of the blocks, ready to translate the political commitment of the Yaoundé Declaration into action and resources – and I’m so proud to see this accelerated action, based on the declaration. We live at an exciting time, with powerful new tools, including the world’s first malaria vaccine and more effective bed nets. In tandem with existing tools, and with strong community engagement on vector control, we have a real opportunity to realise the vision of the Yaoundé Declaration. But acquiring and using these new tools requires significant and sustained resources.”

The WHO DG said significant, sustained investments in malaria control would not only save lives from this one disease, but would make a huge dent in child and maternal mortality in Nigeria, and contribute to long-term social and economic development.

“If a country as large and complex as Nigeria, with a malaria burden as large as yours, can win the fight against malaria, then every country can. Together, we can not only dream of a malaria-free world, we can make it happen,” he said.

Executive Director, The Global Fund, Peter Sands, after a recent visit to Kano, wrote in an opinion piece published in Newsweek: “Insecticide-impregnated mosquito nets, seasonal chemoprevention, and other interventions significantly reduce the risk of infection. Prompt diagnosis and treatment, delivered in the community, is highly effective at preventing severe disease. Yet in Nigeria alone, over 500 people — mainly children and pregnant women — die every day from malaria.

“As the world’s biggest provider of external funding for malaria, my organisation, the Global Fund, invests over US$125 million a year in fighting the disease in Nigeria, working hand-in-hand with the government’s National Malaria Elimination Programme, partners like the U.S. President’s Malaria Initiative and the World Health Organisation, as well as many civil society and community organisations. We have made significant progress. Despite Nigeria accounting for more than a quarter of malaria cases in the world, the malaria mortality rate has fallen by 55 per cent since the beginning of the century. The health workers I met in Kano told us that the introduction of seasonal malaria chemoprevention had improved the situation compared to even a few years ago.

“Yet no one can see so many children fighting for their lives without thinking that if this is better, it’s not nearly good enough. We must do more — and do so now.

“That sense of urgency intensifies when we consider all the factors fueling the threat. Climate change is changing malaria’s epidemiology, affecting its geographical spread, and making it more volatile. Malaria is appearing in the highlands of countries like Ethiopia and Kenya, where previously it was too cold for the mosquitoes. Extreme weather events such as cyclones and floods are causing surges in malaria infections in the most climate-exposed countries, as happened in Mozambique, Malawi, and Pakistan.

“Meanwhile, mosquitoes are becoming resistant to the most commonly used insecticides and the malaria parasite is becoming resistant to artemisinin, the most often used treatment.

“We have answers to some of these challenges, including innovative mosquito nets that are impregnated with a combination of two insecticides, and we also have the prospect of new vaccines, diagnostics and monoclonal treatments. But none of these is a ‘silver bullet,’ and they will all take time….”

To end malaria by 2030, Minister of Health and Social Welfare, Prof. Muhammad Ali Pate, said the ministry has identified key shifts and strategic actions to combat malaria in Nigeria, including establishing an independent Advisory group on Malaria Elimination in Nigeria (#AMEN); developing a pragmatic, costed plan for malaria elimination making explicit the required tradeoffs; intensified malaria case management, including National Health Insurance Authority (NHIA) reforms, domesticated Affordable Medicines for malaria effort, expanding primary health and frontline workforce; mobilising domestic and global funding for malaria; and relentless focus on operational excellence to deploy and optimise existing tools for high coverage, including Long Lasting Insecticide treated Nets (LLINs), Seasonal Malaria Chemoprevention (SMC), Intermittent Preventive Treatment (IPT), Integrated Vector Management (IVM) and phased introduction of safe, efficacious vaccines.

Pate also recommended enhancing community and leadership involvement in malaria elimination; strengthening data integrity and accountability; intensifying preparedness and response to climate change’s impacts on malaria; and exploring bold innovations in service delivery and financing mechanisms.

Meanwhile, the researchers from the London School of Tropical Medicine say that it is positive that organisations such as Regional Artemisinin-resistance Initiative (RAI) and the Asia Pacific Malaria Elimination Network (APMEN) have been established, and the WHO launched a strategy for mitigating ART-R in Africa. However, they say there have been both insufficient political action and too few funding commitments to make any significant headway in stopping the spread of malaria drug resistance across Africa.

They called for governments in the resistance hotspots and beyond to acknowledge the urgency of the issue and agree to coordinated actions such as updating treatment guidelines based on emerging resistance patterns. Regional coordinating mechanisms, with rapid sharing of standardised and validated data, knowledge and experience, will be critical, they add.

They also want to see better disease surveillance through genomic platforms, therapeutic efficacy studies and parasite phenotypic analyses to “monitor the spread of resistant parasites and assess the impacts of antimalarial mitigation efforts.”

This can build on the expansion in laboratory capacity in Africa largely driven by the COVID-19 pandemic.

However, this requires reagents and equipment, norms and processes for data generation and sharing, as well as development of capacity to translate molecular, clinical, and parasitology data into policy decisions.

Sub-Saharan Africa needs a tailored approach that cannot be cut and pasted from elsewhere in the world. They call for multiple interventions, including vector control, case management, chemoprevention, vaccination and social and behavioural change communication.

Priority interventions can include the tailored deployment of triple or sequential ACTs or multiple first-line therapies, they say. The addition of transmission-blocking drugs such as single low-dose primaquine may help to reduce the spread of partial artemisinin resistance.

Finally, they call for more research to identify “mediators of P. falciparum resistance to partner drugs”. Recent reports suggest that parasites with reduced susceptibility to lumefantrine are already circulating in Uganda, where K13 mutations are now present.

“Increased national and regional collaboration between research, health and other relevant sectors needs programmatic support to accelerate the identification of the drivers of resistance and to mitigate their impact,” the scientists say.