Breakthroughs Blog: Malaria

Pregnant women in their first trimester are at risk of malaria Eileen Buxton is a Ghanaian nurse who contracted malaria while pregnant with twins. As a health care professional, she recognized the symptoms such as high fever, severe nausea, and vomiting. She sought care and was given artemether-lumefantrine, a medicine that was recently recommended by the World Health Organization (WHO) to treat malaria in the first trimester of pregnancy.Unfortunately, the situation where medicines are available and determined to be safe for use in first-trimester pregnancy is uncommon. According to the Concept Foundation, since the 1990s, only two drugs have been developed specifically for pregnant women. Furthermore, in the clinical research stage of medicine development, pregnant women, especially those in their first trimester, have been historically excluded for fear of causing harm to the mother and the baby. As a result, health care professionals and pregnant women are left with limited information, making it difficult to make informed decisions about the best course of treatment. Well-tolerated and effective antimalarials, as well as medicines for other diseases, must be developed and made available, accessible, and affordable for pregnant women like Eileen. Malaria infection and treatment during the first trimester of pregnancyMalaria, although preventable and treatable, can become fatal if left untreated, and in pregnancy, the disease has severe consequences for both the mother and the baby she is carrying. Malaria in pregnancy (MiP) can result in the severe, rather than uncomplicated, form of the disease for the mother, resulting in gestational hypertension, premature labor, miscarriage, and the fetus being small for its gestational age. Newborns can be born prematurely and with low birth weight, leading to further health complications, such as cognitive delays. During the first trimester, women are especially at risk of malaria infection because they are unprotected, as no preventive therapies are available until later in pregnancy. Data show that around 65 percent of cases of MiP appear late in the first trimester because the placenta becomes more susceptible to infection, demonstrating a clear need for recommended medicines that can both prevent and treat women in early pregnancy. Although the aforementioned effects of malaria in the second and third trimesters are well known, there has been little data collected on the effects of malaria in the first trimester: few women in malaria-endemic countries attend health facilities in early pregnancy due to a mix of cultural and logistical factors, creating an obstacle to generating research.Preventive therapies for the first trimester are urgently needed: currently, there are none. Intermittent preventive treatment of malaria in pregnancy, an intervention used in sub-Saharan Africa, is only recommended by WHO from the second trimester onward to protect pregnant women from the disease.And although WHO recently recommended the artemisinin-based combination therapy (ACT) artemether-lumefantrine for use in the first trimester, the organization’s Strategy to respond to antimalarial drug resistance in Africa also points out that most countries rely on this drug and thus recommends using a wider range of ACTs to mitigate the development of drug resistance. Ethics and regulatory frameworks for including pregnant women in clinical researchThe four main ethical principles of clinical research are beneficence, nonmaleficence, autonomy, and justice. These principles must be adhered to when designing clinical trials that safely and equitably include pregnant women in their first trimester. In fact, excluding this population perpetuates a cycle of underrepresentation in clinical research, while including them adheres to the principle of justice by ensuring that individuals, regardless of status or condition, have equal access to the benefits of medical research. Drug development takes, on average, 10 to 15 years before registration. When pregnant women are excluded from clinical research, there are no data on how well tolerated or effective it is for pregnant women when the drug reaches market. The COVID-19 pandemic demonstrated that it is possible to rapidly develop and distribute drugs, and with the Sustainable Development Goals (SDGs) set to expire in seven years, the malaria community needs to work at an accelerated pace to achieve Target 3.3 of the SDGs: end the epidemics of AIDS, tuberculosis, malaria, and neglected tropical diseases and combat hepatitis, water-borne diseases, and other communicable diseases. Greater priority must be placed on expediting the discovery, development, and delivery of medicines that meet the needs of at-risk groups, like pregnant women in their first trimester.Global health has experienced a paradigm shift: it is now widely acknowledged that pregnant women must be protected through, and not from, research, a principle that is underscored by recent international commitments. In 2022, at the 75th World Health Assembly, WHO member states adopted Resolution 75.8: Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination. While it does not specifically mention pregnancy, this resolution provides a basis for countries in both the Global North and the Global South to develop clinical ecosystems that are “health-needs driven, evidence based, well designed and well implemented and be guided by established ethical guidance.”In 2021, the G7 Health Ministers adopted the G7 Therapeutics and Vaccines Clinical Trials Charter, which commits to “stronger collaboration in large-scale international trials to enable greater diversity of participants, including pregnant people and children” and supporting low- and middle-income countries, where malaria is most prevalent, in sustainably strengthening capacity. Malaria in pregnancy remains a major public health concern that demands urgent attention and action from global health stakeholders. Clinical research plays a critical role in advancing the development of effective interventions with an adequate safety profile. Ensuring that pregnant women are part of this research from the start can help save millions of lives and adhere to fundamental principles of justice and equity. 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. In June, South Sudan is expecting to begin the rollout of the preventive malaria intervention seasonal malaria chemoprevention (SMC), although there are concerns that high parasite resistance in eastern and southern African countries will limit its long-term efficacy. In June 2022, the World Health Organization (WHO) updated its recommendations that previously restricted SMC’s use to the Sahel region, where malaria transmission is highly seasonal, to encourage its use in other regions after pilot studies showed positive results in countries with high resistance, including South Sudan. Experts have emphasized the need for rigorous monitoring and evaluation to assess SMC’s efficacy in areas of high resistance and to detect any parasite resistance in the Sahel, as well as the development of alternative tools and drugs for malaria chemoprevention.Last week, the European Medicines Agency recommended authorization of GSK’s Arezvy vaccine for respiratory syncytial virus (RSV) in adults 60 years of age and older, which if approved, will be the world’s first available vaccine for RSV. Regulatory agencies in the United Kingdom and United States are expected to make decisions on GSK’s vaccine in the coming months. Pfizer and Moderna are also developing vaccines for the virus, with Pfizer’s candidate already having gained the backing of a panel of US Food and Drug Administration (FDA) advisors earlier this year.Bavarian Nordic, the maker of the Jynneos vaccine, which is approved by the FDA to protect against both smallpox and mpox, is planning to dramatically scale up production capacity for their vaccine. The company’s CEO connected the move to the rapid spread of mpox last year, which highlighted the need to be able to manufacture at a much greater scale than currently available: from tens of millions to hundreds of millions of doses. Bavarian Nordic plans to simplify its production process to facilitate partnerships with other manufacturers in order to have adequate production capacity for stockpiling and in case of a future emergency.

Malaria is one of the world’s oldest and deadliest diseases. Thanks to international efforts to develop and scale up prevention tools and treatments, significant gains have been made over the past few decades in fighting this dangerous disease. But challenges, such as growing drug and insecticide resistance and disruptions from COVID-19, have hampered control efforts. In 2021, there were 247 million malaria cases as cases have continued to rise between 2020 and 2021—indicating progress against the disease has stalled and underscoring the need for continued research and development of new tools.In recognition of World Malaria Day, test your knowledge of this deadly disease and the innovations being advanced to end malaria:

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email.Last week, Ghana became the first country to approve a new malaria vaccine developed by the University of Oxford’s Jenner Institute. The vaccine, R21, is the second-ever vaccine for malaria authorized for use by regulators. Ghana’s Food and Drugs Authority approved the shot for use in children between 5 and 36 months old based on final data from an ongoing phase 3 trial in almost 5,000 children. The results have yet to be published but were shared with regulatory agencies. The vaccine could become an important tool in the fight against malaria and in reducing child mortality, especially if Ghana’s approval is echoed in other countries and by the World Health Organization. The COVID-19 pandemic revealed the consequences of limited genome sequencing capabilities on the African continent and has pushed national laboratories to ramp up their ability in preparation for future pandemics. Thirty-nine African countries now have the equipment and skilled workforce for sequencing, as part of a continent-wide network with specialized training centers and regional hubs. However, capacity levels across laboratories vary, and there is a need to move beyond sequencing the virus that causes COVID-19 to broader applications and for increased training in data analysis.The Biden administration last week announced the launch of Project Next Gen, the US$5 billion-plus program that succeeds the President Trump-era Operation Warp Speed to accelerate the development of new coronavirus vaccines and treatments to address COVID-19 and future coronavirus threats. The program will primarily focus on three objectives: creating long-lasting monoclonal antibodies, advancing vaccines that produce mucosal immunity, and developing pan-coronavirus vaccines. Administration officials expressed their hope that the program can generate strong next-generation vaccines and treatments, delivering breakthroughs that could also potentially benefit other health R&D areas as well