Combatting Malaria in Africa: Challenges, Innovations and Hope for the Future

Much like any struggle for independence, the journey to eradicate malaria is filled with challenges, especially in Africa. The efficacy of existing, lower-cost interventions such as insecticides, anti-malarial drugs, and rapid diagnostic tests is declining. Although malaria is prevalent throughout tropical and subtropical regions worldwide, Africa bears a disproportionately high share of the global malaria burden, both in terms of cases and deaths, and urgently needs our attention and support.

According to the World Health Organization (WHO), in 2022, the African Region accounted for 94% of global malaria cases and 95% of malaria deaths. This translated to 233 million cases and 580,000 deaths, pointing to a slight reduction from 2021. Despite significant progress in recent years in increasing coverage of preventive measures and improving access to treatment, the war against this deadly disease is far from being won.

Billions Lost, Lives Cut Short

Africa bears the brunt of the world's malaria burden, with the Centers for Disease Control and Prevention (CDC) estimating that the continent alone loses US$12 billion in economic productivity each year due to loss of work time. In Uganda alone, Dr Jimmy Opigo, the Health Ministry's Manager for the malaria control program, estimates that malaria kills approximately 16 Ugandans per day and causes an estimated annual economic loss of UGX 1.76 trillion (US$500 million) due to treatment and lost work time.

Moreover, children under the age of five are the most vulnerable, accounting for over 80% of all malaria deaths in 2022, according to the latest data from WHO. Of these fatalities, about 96% occurred in twenty-nine countries worldwide, with four African countries accounting for more than half of all cases: Nigeria (27%), the Democratic Republic of the Congo (12%), Uganda (5%), and Mozambique (4%).

Setbacks from COVID-19, Yet Resilience Endures

While malaria case incidence in the WHO African Region decreased from 373 to 225 per 1000 people at risk between 2000 and 2019, it rose to 234 in 2020, primarily due to service disruptions during the COVID-19 pandemic. Lockdowns and supply chain issues disrupted routine immunization and cases of infectious diseases such as malaria, HIV/AIDS, and TB, leading to a surge in both incidence and mortality rates, exacerbating already stalled progress against the disease.

Data from the 2022 World Malaria Report indicates that malaria cases grew to 241 million in 2020, with 627,000 deaths, representing 14 million more cases and 69,000 more deaths than in 2019. About two-thirds of these additional deaths (47,000) were due to disruptions in malaria prevention, diagnosis, and treatment during the pandemic.

Given the significant impact of COVID-19, Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, was keen to highlight this during the launch of the 2022 Malaria report, saying, "Even before the COVID-19 pandemic struck, global gains against malaria had leveled off." He went on to add, "Now, we need to harness that same energy and commitment to reverse the setbacks caused by the pandemic and step up the pace of progress against this disease."

Despite the challenges imposed by COVID-19, by the end of 2020, about three-quarters (72%) of insecticide-treated mosquito nets (ITNs) had been distributed in malaria-endemic countries as planned. Thirteen nations in Africa's Sahel sub-region provided preventive antimalarial drugs to 11.8 million more children during the high-transmission rainy season in 2020 than they did in 2019 when the COVID-19 epidemic began.

Perfect Storm

Climate change has worsened malaria transmission dynamics by changing the disease's geographic distribution and lengthening transmission seasons. Warmer temperatures, changes in rainfall, human activity, increased vector survival and bite rates, pathogen replication inside vectors, and shorter reproduction rates have all contributed to their spread. As a result, mosquito-borne diseases are expanding and re-emerging in locations where they have remained dormant for years.

The invasion of Anopheles stephensi in Sub-Saharan Africa, where malaria is most prevalent and more than 40 percent of the population lives in cities, has sparked a concern since it is suspected to have fueled the comeback of malaria in Djibouti. Furthermore, based on new mathematical modeling and observations in Djibouti, experts believe the species can potentially raise Plasmodium falciparum incidence by 50 percent.

In Kenya, the Kenya Medical Research Institute (KEMRI) has also detected Anopheles stephensi in the Laisamis and Saku sub-counties of Marsabit County in northern Kenya. Studies indicate that this unique vector can proliferate in various environments, including jerry cans, tires, open tanks, sewers, overhead tanks, and underground tanks. This sets it apart from Anopheles gambiae and Anopheles funestus, which typically thrive in water pools, rice paddies, surface run-offs, hoof prints, or streams.

Its proliferation in urban and peri-urban areas poses a significant threat to malaria transmission in formerly Anopheles-free areas since it transmits both Plasmodium falciparum and Plasmodium vivax malaria parasites.

Race Against Resistance

Climate change isn't the only challenge in the fight against malaria. Increasing resistance to current control methods, such as insecticides and antimalarial drugs, also poses a significant threat to malaria control initiatives. Experts, including Dr. Dunia Munyakanage, a vector control supervisor at the Rwanda Biomedical Centre (RBC), have highlighted that they have developed resistance even against artemether-lumefantrine, an essential malaria treatment.

Scientists are now compelled to design novel treatments for the Anopheles stephensi mosquito, which has developed resistance to artemisinin, a crucial component of coartem. In response to these developments, the World Health Organization (WHO) has intensified its focus on recommending the replacement of antimalarial drugs if efficacy levels drop below 90%.

As a result, artemisinin-based combination therapies (ACTs) are now regarded as highly effective. This development has propelled Universal Corporation Limited (UCL), based in Kenya, to make history in November 2023 by becoming the first African company to secure WHO prequalification for the manufacture of sulfadoxine-pyrimethamine with amodiaquine (SPAQ), a vital antimalarial medication.

Enhancing Malaria Diagnostics

Although effective malaria management relies heavily on accurate and prompt diagnosis, advancements in diagnostic technologies are now becoming crucial. These technologies include rapid diagnostic tests (RDTs) and molecular diagnostics, which facilitate the swift identification of malaria infections, particularly in regions with limited resources.

However, with the emergence of Plasmodium falciparum parasites carrying deletions in the Pfhrp2/3 genes, the reliability of conventional RDTs has been put on notice. These genes encode antigens targeted by many RDTs, and their absence can lead to false-negative results due to reduced sensitivity. Therefore, this necessitates the diversification of diagnostic tools to address this vulnerability.

Therefore, molecular diagnostics, such as PCR assays, are becoming common as they offer higher sensitivity and specificity, whereas RDTs fail to detect genetic variations that impact diagnostic accuracy. They are particularly proficient at identifying non-falciparum species, which are often missed by traditional RDTs. Nonetheless, making molecular techniques more accessible and affordable in resource-limited settings remains a hurdle.

The eradication of malaria in Africa is now within reach, provided that critical obstacles are addressed through focused research and development initiatives. Improving the sensitivity of diagnostic instruments for non-falciparum species and enhancing their applicability across various diagnostic settings are crucial steps in this process. This could include identifying novel biomarkers, refining assay procedures, innovating point-of-care diagnostic equipment, and accelerating vaccine development efforts.

For instance, Malawi stands out as a leader in innovation by using the microfluidic point-of-care (mPOC) immunoassay. The mPOC has demonstrated comparable accuracy to a commercial HRP2 enzyme-linked immunosorbent assay (ELISA) test while being twelve times faster and easier to use. According to Peter Lillehoj, associate professor of mechanical engineering at Rice University's Brown School of Engineering, mPOC can rapidly and effectively diagnose malaria, particularly cerebral malaria, at the point of care. This advancement could lead to the early detection and treatment of severe cases.

Similarly, Kenya, through the Ministry of Health (MOH), has taken steps to install an automated malaria testing system (XN-31 analyzer) at the Ahero County Hospital Laboratory in Kisumu County. With exceptional sensitivity and specificity, this state-of-the-art analyzer is designed to detect and count malaria-infected red blood cells within a minute. Therefore, the implementation of the XN-31 analyzer holds promise for addressing malaria diagnostic challenges and enhancing the accuracy and efficiency of treatment for this endemic disease.

A Shot of Hope

While malaria eradication has long been the ultimate goal, numerous initiatives have predominantly focused on precise malaria diagnosis, vector control, and advancing new antimalarial drugs. However, recent strides in malaria vaccines have brought us closer to realizing this elusive objective, instilling optimism for a future where vaccinations play a pivotal role in disease prevention.

So far, the WHO has recommended two vaccines, RTS,S/AS01 (Mosquirix) and R21/Matrix-M, for children living in areas with moderate to high transmission of Plasmodium falciparum malaria. This prequalification makes the two vaccines available as critical tools to prevent malaria in children, a prerequisite for vaccine procurement by UNICEF, and funding support for deployment by Gavi, the Vaccine Alliance.

Since 2019, over 2 million children in Ghana, Kenya, and Malawi have been vaccinated with the RTS,S malaria vaccine as part of a pilot program. Furthermore, over 30 African countries have expressed interest in receiving the vaccine. This is in addition to the 18 million doses of RTS,S that have been sent to 12 African nations for use between 2023 and 2025.

The ongoing vaccination campaign has yielded promising results, with a notable decrease in malaria illness, a 13% reduction in overall child mortality, and significant declines in hospitalizations. Under the guidance of WHO, the Malaria Vaccine Implementation Programme (MVIP) has been instrumental in coordinating these efforts. Additionally, Gavi's financing of US$160 million for the 2022–2025 period ensures the expanded deployment of malaria vaccines in Gavi-eligible countries.

Studies demonstrating the safety and efficacy of these vaccines have resulted in a notable decrease in cases of severe malaria and a reduction in child fatalities in Africa. Thabani Maphosa, Managing Director of Country Programmes Delivery at Gavi, highlighted renewed hope in the fight against malaria, stating, “This vaccine has the potential to be very impactful in the fight against malaria, and when broadly deployed alongside other interventions, it can prevent tens of thousands of future deaths every year.”

WHO anticipates that following these rollouts, the global demand for malaria vaccines will increase to 40–60 million doses by 2026, with a goal of 80–100 million doses annually by 2030. In addition to the RTS,S vaccine, developed and produced by GSK and in the future supplied by Bharat Biotech, a second vaccine, R21, developed by Oxford University and manufactured by the Serum Institute of India (SII), is expected to play a significant role in future vaccination efforts.

From Burden to Success

Malaria's devastating toll on Africa has been undeniable, claiming millions of lives annually and inflicting significant economic repercussions. Although climate change, insecticide resistance, and evolving vector species still pose new challenges to malaria control efforts, therefore risking hard-won gains, there is reason for optimism. Africa must sustain its momentum and foster collaboration to address the multifaceted challenges posed by malaria.

Innovative approaches, more robust healthcare systems, and increased international cooperation are essential to realizing a malaria-free world. Encouragingly, the number of malaria-endemic countries has decreased from 108 in 2000 to 84 in 2021, signifying substantial advancements in eradication efforts. Cabo Verde now stands out as the most recent success story, having reported no malaria deaths since 2018. This has allowed it to join the ranks of Mauritius and Algeria as the third country in the WHO African region to achieve malaria-free certification.