Research Briefs


close-up of mosquito on human skin


Mosquitoes of the genus Anopheles can transmit Plasmodium falciparum, the microscopic parasite that causes the disease.

There’s no effective vaccine against malaria, the mosquito-borne disease that is a serious global health problem, affecting over 200 million people each year and causing more than 400,000 deaths annually in Africa alone. Mosquitoes of the genus Anopheles can transmit Plasmodium falciparum, the microscopic parasite that causes the disease. Children may contract malaria dozens of times before developing immunity in their teens.

Until now, no one understood what gave malaria the strength to evade the immune system. Now NIAID researchers and their international collaborators may have a clue. They found that by altering a single nucleotide in a gene that codes for one transcription factor, P. falciparum was much less able to escape the immune systems of mouse models. The researchers suggest that further exploring these genes may help elucidate a target for experimental therapeutics or even a preventative vaccine against malaria.

To watch a video interview with the NIAID researchers who conducted the study, go to (NIH authors: M. Akkaya, A. Bansal, P.W. Sheehan, M. Pena, A. Molina-Cruz, C.K. Cimperman, C.-F. Qi, T. Yazew, D. Sturdevant, S.L. Anzick, G. Thiruvengadam, L.H. Miller, and S.K. Pierce, Sci Adv 6:eaaw6957, 2020; DOI:10.1126/sciadv.aaw6957)


Exposure to phthalates and stressful life events in pregnancy have each been associated with preterm birth (PTB), but no study has examined the joint impact of both. NIEHS researchers and collaborators observed an association between the urinary phthalate metabolites concentrations and PTB that was modified by whether a mother was exposed to one or more psychosocial stressors (such as job loss, serious illness, family death, relationship difficulties, and legal or financial problems) during pregnancy. Phthalates are chemicals used in personal-care products and plastics; people are exposed to phthalates through dermal absorption and by ingesting foods and beverages that have been in contact with containers and products that contain the chemical. In the study, the researchers used data from The Infant Development and the Environment Study—a prospective birth cohort conducted at four U.S. sites (n=783)—to examine urinary phthalate metabolite concentrations in samples collected from women during their pregnancy. Mothers reported their exposure to stressful life events in each trimester in a questionnaire administered in the third trimester. Additional research to understand the joint impacts of chemical and nonchemical exposures, with an emphasis on timing of exposure, is needed to advance the state of the science on how the environment influences pregnancy. (NIH authors: K.K. Ferguson and E.M. Rosen, Environ Int 133:Part B, 2019; DOI:10.1016/j.envint.2019.105254)


Pregnant women exposed to persistent organic pollutants, or POPs, had slightly smaller fetuses than women who hadn’t been exposed to these chemicals, according to an analysis of ultrasound scans by NICHD researchers and others. The researchers also found that the women in their study had lower concentrations of POPs than women in the 2003–2004 U.S. Health and Nutrition Survey, the most recent comprehensive study of these compounds in U.S. pregnant women. The latest findings suggest that the chemicals, which are no longer produced in the United States but persist in the environment, may have lasting health effects even at low concentrations. POP chemicals were once used in agriculture (including the pesticide dichloro-diphenyl-trichloroethane, or DDT), disease control, manufacturing, and industrial processes. POPs are slow to break down, may persist in water and air, and may be passed through the food chain. Some compounds have been linked to reproductive disorders and a higher risk of birth defects. In the current study, researchers analyzed records, stored blood samples, and a series of ultrasound scans taken from weeks 16–40 of 2,284 pregnant women enrolled in the NICHD Fetal Growth Study from 2009 to 2013. (NIH authors: M. Ouidir, G.M. Buck Louis, J. Kanner, K.L. Grantz, C. Zhang, R. Sundaram, F. Tekola-Ayele, and P. Mendola, JAMA Pediatr, 2019; DOI:10.1001/jamapediatrics.2019.5104)


Over the past 20 years, three families have been unsuspectingly linked by an unknown illness. Researchers at NIH and other organizations have now identified the cause of the illness, a new disease called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. NHGRI scientific director Daniel Kastner, a pioneer in the field of autoinflammatory diseases, and his team discovered CRIA, which has symptoms including fevers, swollen lymph nodes, severe abdominal pain, gastrointestinal problems, headaches and, in some cases, abnormally enlarged spleen and liver.

The researchers sequenced gene regions and discovered only one gene—RIPK1—to be consistently different in all patients. Each affected person had one mutant and one normal copy of the gene, while the unaffected family members had two normal copies of the gene. The researchers also looked at 554 people with sporadic unexplained fever, swollen glands, and other symptoms or diseases, and then at over a quarter million people from public sequence databases to see whether they encountered the same RIPK1 mutations. When they did not find such mutations elsewhere, it was clear that they were onto something new.

The RIPK1 gene encodes for the protein receptor-interacting serine-threonine kinase 1 (RIPK1), which is involved in the body’s response to inflammation and programmed cell death. Cutting RIPK1, thereby disarming it, is crucial to controlling cell death and inflammation. To understand the molecular mechanisms, the team collaborated with researchers in Australia, who made specialized mouse models with RIPK1 mutations similar to those seen in CRIA patients. The Australian team discovered that mouse embryos with two mutant copies of RIPK1 (and no normal copy) did not survive in the uterus due to excessive cell-death signals, which further confirmed the importance of cutting RIPK1 to limit its function in normal cells. However, mice bearing one mutant copy of RIPK1 and one normal copy, as is the case for CRIA patients, were mostly normal but had heightened responses to a variety of inflammatory stimuli, which the researchers think may suggest a possible mechanism for how the human disease occurs.

Seven patients with the condition were given therapies that are known to reduce inflammation, but only the drug tocilizumab worked. Tocilizumab, which suppresses the immune system, reduced the severity and frequency of CRIA syndrome symptoms in five of seven patients, in some cases with life-changing effects. Researchers are now trying to understand the detailed molecular mechanism that enables tocilizumab to treat CRIA. Specific inhibitors of RIPK1, which are under development, may also hold promise in both CRIA and other seemingly intractable inflammatory conditions. (NIH authors: S.E. Boyden, H. Oda, G.M. Wood, D.L. Stone, M. Stoffels, K.J.M. Zaal, P.M. Hoffmann, W.L. Tsai, M.D. Blake, H.S. Kuehn, D. Yang, L. Zheng, N. Sampaio Moura, D.B. Beck, G. Gutierrez-Cruz, A.K. Ombrello, G.P. Pinto-Patarroyo, H. Wang, J.J. Chae, N.I. Dmitrieva, B.K. Barham, A. Jones, T.M. Romeo, Q. Zhou, I. Aksentijevich, J.C. Mullikin, M.J. Lenardo, M. Boehm, S.D. Rosenzweig, M. Gadina, and D.L. Kastner, Nature 577:103–108, 2020; DOI: 10.1038/s41586-019-1828-5)