Research Roundup: Generic HIV prevention drug, TB vaccine development deal, Universal flu vaccine trial

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.Last Thursday, the World Health Organization (WHO) declared the end of the global health emergency for mpox following a recommendation from WHO’s emergency committee on mpox, which also recommended continued management to prevent the virus from evolving. Bavarian Nordic’s vaccine for smallpox was deployed in the United States and Europe under emergency authorizations and recommended by WHO primarily for post-exposure during the mpox emergency, although the limited available stock that was already earmarked for wealthy countries created access challenges in low- and middle-income countries. Randomized control trials planned in endemic countries will provide more essential data about the efficacy of the vaccine against mpox. Additional data is also needed to fully understand how the strain of the virus evolved to sustain prolonged transmission between humans.Last week, the US$30 million Human Pangenome project, launched in 2019 and funded by the US National Human Genome Research Institute, published the first phase of the first human pangenome, which aims to be a genome that is more representative of the diversity of DNA in humans around the world. The genome could be an important guide for researchers building genetic tests and looking for new drug targets. This initiative addresses diversity gaps in the first reference genome, released in 2001, which have undermined the ability to develop tests that work across diverse populations.A new global research consortium organized by the Centres for Antimicrobial Optimisation Network aims to fight antimicrobial resistance by improving clinical use of antimicrobials and improving practices and guidelines for prescribers, users, and policymakers. Research hubs in Kampala, Cape Town, São Paulo, Liverpool, and London—where there is a high burden of drug-resistant infections and where there are communities highly affected by the burden of infectious disease—will generate essential data on the optimal use of antibiotics. Researchers hope this will in turn lead to more effective treatment and prevention of bacterial infections in the face of rising antimicrobial resistance worldwide.