On World Malaria Day, Nathalie Sohier, MD, MPH, shares her personal perspective on the current state of malaria treatment.

Nathalie Sohier, MD, MPH is a Senior Medical Director and Global Therapeutic Area Head for Infectious Diseases and Vaccines within PAREXEL’s Global Medical Services division.

Nathalie started her professional life working with international medical Non-Governmental Organizations (NGOs), that in 1988 brought her to the jungle on the Thai-Burmese border where she worked with the Môn people.

At that time, malaria was the number one disease in terms of morbidity and mortality in this area. Eighty percent of hospitalized patients had malaria and mortality was substantial amongst patients with severe and cerebral malaria. Nathalie worked in a hospital made of bamboo without resuscitation equipment or oxygen available. Only IV quinine, a medication used to treat malaria, and intensive nursing care for the most serious cases was available. For infants infected with the disease, Nathalie had to crush quinine pills and dilute them in sugary-water as there was no baby formula available. Many adolescent patients came to the hospital fleeing from reprisals following the bloody demonstrations of October 1988. Seeking shelter in the surrounding jungles had exposed them to malaria.

A few years later, in Kenya, Nathalie witnessed how the Human Immunodeficiency Virus (HIV) was transmitted to babies hospitalized for severe anemia due to malaria. Malaria’s main cause of death for babies is severe anemia. In such cases, a blood transfusion is the most impactful remedy. In this area, finding blood was the first challenge. An additional difficulty was convincing healthy adults to donate blood.  Due to rampant HIV infections in the region, sub-optimal screening and the need to access needles to give life-saving blood transfusions for malaria, many babies who survived malaria infection were subsequently infected with HIV.

These life-changing experiences with malaria encountered early in her professional life helped guide Nathalie’s career and drove her passion for helping patients with infectious diseases. On World Malaria Day, Nathalie shared with us her personal perspective on where the disease treatment stands three decades later. 

PAREXEL Insights: How widespread is malaria today?

Nathalie Sohier: Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. In 2017, there were an estimated 219 million cases of malaria in 87 countries.

Approximately 70 percent of the world’s malaria burden is concentrated in 11 countries: 10 on the African continent, plus India. The estimated number of malaria deaths stood at 435,000 in 2017. Children under 5 years of age are the most vulnerable group affected by malaria; in 2017, they accounted for 61 percent (266 000) of all malaria deaths worldwide. In Asia both adults and children suffer from malaria access contrary to Africa where most patients are children under the age of five.

The World Health Organization (WHO) African Region carries a disproportionately high share of the global malaria burden. In 2017, the region was home to 92 percent of malaria cases and 93 percent of malaria deaths.

There are five parasite species that cause malaria in humans, and two of these species pose the greatest threat. In 2017, the parasite P. falciparum accounted for 99.7 percent of estimated malaria cases in the WHO African Region, as well as in the majority of cases in the WHO regions of South-East Asia (62.8 percent), the Eastern Mediterranean (69 percent) and the Western Pacific (71.9 percent). P. vivax is the predominant parasite in the WHO Region of the Americas, representing 74.1 percent of malaria cases.

Although these numbers seem rather high, malaria disease burden has much improved during the past 30 years. In fact, we saw a decrease of 37 percent in new cases among at-risk populations between 2000 and 2015. Two major factors contributed to this large decrease, including 1) WHO’s active promotion of a treatment called artemisinin and its derivatives and 2) mass distribution of insecticide-treated bed nets in areas of high risk.

On the Thai-Burmese border where I worked with the Môn people back in 1988, there are virtually no more malaria cases, and especially no more P. falciparum cases which were responsible for cerebral malaria. The few cases which still occur mainly affect workers in remote areas in the forest.

PAREXEL Insights: What are the main challenges for patients with malaria?

Natalie Sohier: Unfortunately, symptoms of non-complicated malaria are not very specific. They include fever and chills, headache, nausea and vomiting, diarrhea, muscle pain, and fatigue. These usually occur in cycles of two to three days. However, if not treated quickly, complications may occur and lead to death such as severe anemia, coma (cerebral malaria), pulmonary edema, jaundice, or acute respiratory distress syndrome.

Today, malaria remains a life-threatening disease, especially for pregnant women and for children under five. The more severe cases are seen with plasmodium falciparum infections. The main challenge is to diagnose and provide adequate treatment on time for patients living in remote areas, especially during the rainy season.

For patients infected with plasmodium vivax, or plasmodium ovalae, the challenge is the recurrence, even after an access has been treated. These species have the capacity to remain dormant in the liver and to be able to wake-up weeks of even years after a first infection, causing new accesses. Patients must receive a specific treatment to kill the dormant parasites but providing safe and convenient treatment  is still work in progress.

Another challenge is the resistance of the parasites to the drugs. At the patient level, we speak of partial resistance for the time being: the patients can be treated but it takes longer. Combination therapy with artemisinin usually clears malaria from the blood in three days. In case of resistance, patients are treated for up to eight days.

The emergence of multidrug resistance, including resistance to artemisinin and partner drugs which are the best treatment options today, is a public health concern threatening the sustainability of the ongoing global effort to reduce the burden of malaria. Multi-resistant strains have emerged in and were reported from Cambodia in 2013. Since then, they have spread into South-East Asia. The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as artemisinin-based combination therapy (ACT) is the only effective and widely-used antimalarial treatment at the moment.

In February 2017, the first case of artemisin partially resistant parasite was detected in a Chinese patient who came back from Africa. This development raises concern about the efforts to fight a disease that sickens hundreds of millions of people each year.

PAREXEL Insights: Tell us a little about the current treatment landscape for malaria.

Natalie Sohier: The current treatments have both preventative and curative aspects. The widespread use of ACTs, combined with increased Anopheles mosquito vector control through distribution of insecticide-treated bed nets and indoor residual insecticide spraying, has decreased the global malaria burden by an estimated 37 percent between 2000 and 2015. These gains, however, are threatened by the rise of P. falciparum resistance to ACTs and the rise of mosquitoes’ resistance to insecticides.

In addition to treatment of malaria accesses and vector-control measures, systematic treatment is provided to pregnant women on intermittent basis. For children three to 59 months, seasonal malaria chemoprevention is administered in areas of acute seasonal transmission, mostly in countries in the Sahel sub-region.

PAREXEL Insights: What is the most exciting thing happening in research today for malaria?

Natalie Sohier: The most exciting recent development came in 2015 when WHO switched from the goal of malaria control to malaria elimination in at least ten countries by 2020 and also announced its aim to dramatically lower the malaria burden by 2030.

In order to reach these goals, on the parasite side various treatments and strategies are being developed including the distribution of the only malaria vaccine available to date to children in selected countries, the research of new potent first line malaria treatment not prone to resistance generation, and the development of new safe single-dose regimen treatment to break the cycle of disease transmission in symptomatic patients but also for the treatment of asymptomatic carriers.

In terms of diagnostic tools, research is also very active in looking for new and more accurate rapid tests which will facilitate diagnosis and adapted treatment in remote areas.

On the vector side, insecticide-treated bed nets and indoor spraying of long-lasting insecticides are highly effective but are insufficient to eliminate malaria transmission in many settings because of operational constraints, mosquitoes that behaviorally avoid contact with them inside houses and growing resistance to available insecticides. Research is on-going to find new insecticides, target mosquitoes larvae’s using chemical or biological control measure (such as introducing enemies into aquatic habitat) or attracting male and female mosquitos through attractive toxic sugar bait (ATSB) in the outdoor environment.

The global situation of malaria has much improved since 1988 thanks to ACTs and vector control measures. The malaria mortality rate, which takes into account population growth, is estimated to have decreased by 60 percent globally between 2000 and 2015. However, in Africa, ACT treatment for children with malaria remains unacceptably low. More work is needed at the country level to understand how health-care access, service delivery, and ACT supply might be improved to ensure appropriate treatment for all children with malaria.

PAREXEL Insights: What stakeholders need to get involved to improve the outlook for patients with malaria?

Natalie Sohier: Thanks to collective efforts by governments, multinational institutions, the private sector and non-profit organizations, the world has made historic progress to defeat malaria. These partners are responsible for buying and distributing life-saving malaria interventions, training community health workers and, researching and developing innovative tools.

The largest funder of malaria control and elimination is the Global Fund to Fight AIDS, Tuberculosis and Malaria. The World Bank also has been a key funder of malaria programs. As most countries affected by malaria are poor countries, funding must come from various sources. In 2017, International funding represented the major source of funding in low-income and lower-middle-income countries, at 87 percent and 70 percent, respectively.

The Global Technical Strategy (GTS) for Malaria 2016–2030 was adopted by the World Health Assembly in May 2015. It provides a comprehensive framework to guide countries in their efforts to accelerate progress towards malaria elimination. The strategy sets the target of reducing global malaria incidence and mortality rates by at least 90 percent by 2030. Although funding for malaria has remained relatively stable since 2010, the level of investment in 2017 is far from what is required to reach the first 2 milestones of the GTS; that is, a reduction of at least 40 percent in malaria case incidence and mortality rates globally by 2020, compared with 2015 levels.

To reach the GTS 2030 targets, it is estimated that annual malaria funding will need to increase to at least US$ 6.6 billion per year by 2020.

PAREXEL Insights: What can be learned by the evolution of treatment for malaria in treating other infectious diseases?

Natalie Sohier: As for other infectious diseases due to viruses, bacteria or parasites, discovering new drugs is a constant necessity due to the fact that living micro-organisms mutate when replicating and are capable of developing resistant mutations to drugs, thus escaping their effect. The three global killers in infectious diseases which are HIV, tuberculosis and malaria are primarily diseases of poverty. They can only be controlled (and potentially eradicated) with a large panel of interventions which require continuous R&D process for the development of new tools and approaches. The development of preventive and therapeutic vaccines, new diagnostic tools and new efficacious drugs is as important as making sure that these tools reach the patients who need them.

References

1. World Health Organization
2. Prevention Efforts for Malaria, Tinashe A. Tizifa et al. Current Tropical Medicine Reports (2018) 5:41-50
3. New developments in anti-malarial target candidate and product profiles, Jeremy N. Burrows et al. Malaria Journal (2017) 16:26
4. Developing an expanded vector control toolbox for malaria elimination, Gerry F Killeen et al. BMJ Global Health 2017