Concerns about antibiotic-resistant bacteria have been growing in recent years, and researchers at the Yerkes National Primate Research Center (YNPRC) have added another to the list. Klebsiella pneumoniae, a bacterium that causes blood, soft tissue and urinary tract infections, has been found resistant to colistin, a powerful last resort antibiotic. In 2013, the Centers for Disease Control and Prevention (CDC) listed Carbapenem-resistant Enterobacteriaceae (CRE), which include Klebsiella, as one of the top three urgent antibiotic resistant threats.

According to the CDC, healthy people usually don’t contract this type of infection. It usually affects patients in hospitals, nursing homes and other health-care settings. Patients whose care requires devices such as ventilators, urinary catheters or intravenous catheters, and patients who are taking antibiotics for a long period of time are most at risk for CRE infections. Various types of Klebsiella are estimated to be responsible for 10 percent of infections acquired in health-care facilities.

“This is concerning because Klebsiella is a more common cause of infection than Enterobacter,” said David Weiss, a researcher at the Yerkes National Primate Research Center and the director of the Emory Antibiotic Resistance Center. “To our knowledge, this type of [antibiotic-resistant] Klebsiella has not been observed in the United States before.”

Despite the extra time required, Dr. Weiss and his colleagues recommend clinical laboratories consider testing for heteroresistance to colistin if this last line antibiotic is required for CRE treatment.

What doesn’t kill you might just save your life.

At least, that’s the new thinking on how to combat SIV, a variant of HIV. This comes after researchers at the Yerkes National Primate Research Center sequenced the genome of the sooty mangabey – a nonhuman primate that can coexist with SIV – and discovered how an immune system deficiency actually stops SIV from turning into AIDS.

“We found two big differences in proteins of the immune system in the sooty mangabey genome, which we hope will help us better understand why sooty mangabeys avoid AIDS despite SIV infection,” said David Palesch, a Yerkes postdoctoral fellow and co-author of the study documenting the discovery.

These differences aren’t some biological defense system or super-simian invulnerability. Technically, they’re handicaps. Instead of a more robust immune system, the sooty mangabey is playing a man down in the fight against SIV and winning.

So what are these immune deficiencies? A missing piece in the the ICAM2 gene stops the corresponding protein from functioning – a genetic anomaly unique to the mangabey species.

Similarly, the TLR4 protein – a molecule that senses bacteria and triggers an immune defense against it – has limited functioning because of a genetic alteration.

“This finding is intriguing because damage to intestinal barriers and bacterial release contributes to chronic immune activation, which is associated with AIDS progression in HIV-infected humans and SIV-infected non-natural hosts,” said Guido Silvestri, chief of Microbiology and Immunology at the Yerkes Research Center.

Inspired by these findings, the Yerkes team is already planning its next study where the ICAM2 and TLR4 proteins will be manipulated in a living nonhuman primate host to determine how those genetic anomalies halt SIV’s progression.

“It’s a really exciting time in AIDS research,” said Dr. Steve Bosinger, assistant professor of Pathology and Laboratory Medicine and director of Yerkes’ Genomics Core. “We’ve seen that an HIV cure is possible.” Now, that’s something to be excited about.

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Photo credit: Yerkes National Primate Research Center

While the public’s nervous obsession with Zika may be over, medical researchers still have questions. Can the virus survive in a nonhuman host? Can the blood of that nonhuman host infect others? For researchers at the National Primate Research Centers, it’s questions like these that drive their curiosity and compel them to find answers.

Scientists at the Wisconsin National Primate Research Center wanted to know if a mosquito bite can turn a nonhuman mammal into a virus carrier. To investigate this, they let Zika-carrying mosquitoes infect rhesus macaques. They then compared those monkeys and their symptoms to macaques that the researchers had injected with Zika.

The differences were small but significant. “It’s a difference of a couple days to what we call peak viremia,” says Dawn Dudley, a UW-Madison pathologist. Viremia is the medical term for when the virus enters the bloodstream. At that point, it can migrate from the spot of initial contact to other regions of the body where it may lie dormant, waiting to be passed on to someone or something else.

It’s unclear why the virus moves slower when delivered through a mosquito bite. “The biology of the disease probably depends a lot on how the mosquitoes transmit that disease – mechanically how they do it, and biologically what comes along with the virus when the mosquito bites,” says Tom Friedrich, a UW-Madison professor of pathobiological sciences.

The virus was also less likely to affect the central nervous system tissues of mosquito-bitten macaques.

Despite these differences, the virus never became strong enough to infect mosquitoes who fed on the macaques. “But that doesn’t mean other nonhuman primates couldn’t do that,” says Dudley. And with more questions, there’s always more research.

Reviewed August 2019

An estimated 130-150 million people around the globe are living with chronic hepatitis C infection. Thanks to chimpanzees, there is now a one pill per day, 12-week cure that has already improved more than half a million lives.

As a scientific animal model, chimpanzees have played an integral role in advances against this group of deadly viruses. Without the use of these nonhuman primates with their close genetic relationship to people, many of the modern interventions, including a curative regimen for hepatitis C, might not be available today.

In a recent review article published in the ILAR Journal of the Institute for Laboratory Animal Research, Robert Lanford, of the Southwest National Primate Research Center and his co-authors present a wide-ranging, detailed look at how chimpanzee research has positively impacted human health specifically by helping bring about breakthroughs in the treatment of hepatitis.

The National Institutes of Health began chimpanzee breeding in the U.S. in 1960. The NIH has halted all further research using chimpanzee models, and Lanford points out that at research facilities and at Chimp Haven in Louisiana, “the animals are enjoying their retirement.”

In his summary, Lanford writes “entire generations are immune to HAV (hepatitis A) and HBV (hepatitis B) because of vaccines developed in the chimpanzee that are in widespread use globally.” With HBV chronic infection affecting more than 250 million people, he observes that “the loss of the chimpanzee model has stymied development of curative therapies for this infection.” Lanford goes on to suggest the scientific community needs to develop improved mouse models and even a new nonhuman primate model for this disease.

Over time, the article concludes, future generations will look back positively on the impact the chimpanzee animal model has had on human health. Hepatitis will be a disease of the past, much like polio and smallpox are today.

On February 1, 2016, the World Health Organization declared the Zika virus to be a global health emergency. Spread by the bite of an infected mosquito, the Zika virus has moved rapidly across the Western hemisphere and is linked to potential birth defects.

A team of researchers at the University of Wisconsin-Madison, along with collaborators at Duke University and the University of California, Davis, is working to understand the threat Zika could cause to human pregnancies. Through their work with rhesus monkeys at the Wisconsin National Primate Research Center (WiNPRC), the researchers can uniquely understand the virus’ short and long-term effects.

“There are so many things about Zika infection we can’t study as well in pregnant humans – or fast enough to make a difference for a lot of people who may be infected,” says Dr. Dawn Dudley, a UW-Madison pathology research scientist. “The precise pathway that the virus takes from mom’s bloodstream to the fetal bloodstream, across that interface, cannot be studied except in an animal model.”

The research team, led by primate center scientist Dr. David O’Connor, monitored four pregnant rhesus macaque monkeys that were exposed to the Zika virus. Through regular assessment of maternal infection and fetal development, the researchers found evidence that the virus was passed efficiently to each fetus.

The infection spread inflammatory damage through the tissues that supported the fetus and its developing nervous system, suggesting that the virus poses a larger threat to human fetuses than originally theorized. In fact, three of the fetuses had small heads (although not quite small enough to diagnose microcephaly) and unusual inflammation of the eyes. However, the medical study did not find abnormal brain development.

These sobering results suggest that, as they grow, human babies who were exposed to the virus may develop more Zika-related disease pathology. Research teams are currently working to understand how Zika interacts with other infections, how the effects of early pregnancy infection differ from later infection, and whether antiviral therapies could manage the effects of congenital Zika syndrome.

Reviewed August 2019

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Photo credit: Wisconsin National Primate Research Center

The rapid spread of the Zika virus has led to widespread media and government attention; however, little is known about the disease itself. How long does the disease stay in the system? Where does the Zika virus attack? And how does it spread to offspring?

A team of interdisciplinary researchers from OHSU in Portland, Oregon, is attempting to find these answers. Collaborating with the Oregon National Primate Center (ONPRC), the team is beginning to unlock the mysteries of the virus – and ultimately pave the way for future therapies and vaccines.

“This study helps us better understand how the virus manifests itself so that scientists can develop therapies and vaccines that would work in humans,” says Dr. Daniel Streblow, Associate Professor of Molecular Microbiology and Immunology in the OHSU Vaccine and Gene Therapy Institute, OHSU School of Medicine. “Our study significantly advances what is known about the growth of the virus in the host.”

The research team, a 20-person cross-section of faculty across the university, examined the Zika virus infection in seven rhesus macaques from March 2016 to August 2016. The study observed the Zika virus at seven, 28 and 35 days post-infection.

Ultimately, it was found that the Zika virus attacks tissues in the nervous system, male and female reproductive and urinary tracts, muscles, joints and lymph nodes. The virus first presents itself as a rash, fever or pink eye, and then persists in the body for at least 35 days.

“What is different about this research is that we also were able to look at specific points in time to see where the virus grew in the tissues so we can identify and target the reservoirs where the virus hides,” says Dr. Streblow.

This medical study was conducted in response to the Zika virus outbreak across the Western hemisphere. In 2016, there were 5,102 reported cases of the Zika virus in the United States, and an additional 36,079 cases reported in US territories.

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Photo credit: Kathy West for the California National Primate Research Center

The West African outbreak of Ebola virus in 2014 made Ebola a household word. The outbreak made clear that infectious diseases know no borders and have global impact.

Ebola first emerged 40 years ago, spreading its deadly symptoms across South Sudan and the Democratic Republic of Congo. According to the World Health Organization, Ebola has a 50% average mortality rate. During the 2014-2016 outbreak, the disease infected over 28,000 people in West Africa and killed over 11,000. Currently, there are no FDA-approved treatments or vaccines for the Ebola virus – but the team at Texas Biomedical Research Institute and the Southwest National Primate Research Center is working to change that.

These scientists are working with the National Institutes of Health, the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense to develop assays and evaluate vaccine and therapeutic candidates.

Most recently, a group of Texas Biomed scientists led by Dr. Ricardo Carrion and Dr. Anthony Griffiths was awarded a $6.6 million contract in November 2017 from the Biomedical Advanced Research and Development Authority (BARDA) to test a drug cocktail for efficacy against Ebola virus disease. These well-regulated, controlled studies that will begin in 2018 are a critical next step before declaring this drug cocktail safe and effective in humans.

“Texas Biomed is the only Institute of its kind in the country, with two extraordinary resources in one place – the BioSafety Level – 4 (BSL-4) facilities and nonhuman primate colonies,” said Scientist and Director of Texas Biomed’s BSL-4 laboratory Dr. Robert Davey.

In 2015, after discovering that tetrandrine works to stop the Ebola virus, Dr. Davey and his lab wondered: how can we move this herbal remedy into the clinic?

He has since teamed up with scientists at the Southwest Research Institute (SwRI) to develop a synthetic route to make safer versions of tetrandrine with better clinical properties as potential therapeutics against the virus. To support their scientific studies, the team of researchers received an NIH research and development contract worth up to $4.1 million.

From helping diagnose a disease to curing them, scientists at Texas Biomed and the Southwest National Primate Research Center continue the fight against pathogenic invaders and the search for new ways to approach global health threats.