As recent news stories attest, measles is one of the most infectious diseases on Earth — and it affects more than just humans. Nonhuman primates are also at risk.

Although the CNPRC requires all employees and visitors to obtain measles vaccination or show proof of immunity, the center’s animals could still be at risk of outside contamination. Before 1996, the only vaccination protocols for nonhuman primates were based on protocols developed for humans, but these were not cost-effective, and primate facilities needed a better option.

This is why, since 1996, Kari Christe, DVM, has worked to test the safest and most efficient way to vaccinate the entire CNPRC rhesus macaque monkey colony. Her team’s work is also providing information to help other facilities make informed decisions on how to protect their animal colonies.

Christe and her veterinary team have made significant progress. Before this research began, many primate facilities did not have the resources to vaccinate their monkeys. But Christe and team have shown it is possible to protect rhesus macaques from measles in a cost-effective fashion using only half the recommended dose of a specific type of vaccine — the measles and canine distemper vaccine — in comparison to the measles, mumps and rubella vaccine used in humans. The new strategy will save research facilities, zoos and conservation organizations at least $3 per animal (there are nearly 4,000 animals at the CNPRC), based on the most recent estimates. 

With safer and more cost-effective vaccine protocols than ever before, Christe and CNPRC veterinarians are working their way toward protecting all nonhuman primates from measles at their facility and beyond. And this means those same animals will be able to participate in NPRC research studies focused on improving health for humans and animals alike.

Reviewed: June 2020

Ebola virus is a continuing threat in Central and West Africa, with an outbreak currently taking place in the Democratic Republic of Congo. But the factors that determine who is most susceptible to Ebola infection are still a mystery.

Now,  researchers at Texas Biomedical Research Institute, home to the Southwest National Primate Research Center —in collaboration with the University of Iowa—are investigating how malaria infections could impact people exposed to Ebola virus, since both diseases are common and recurring in the Congo.

Other co-infections are known to impact each other’s outcome. For example, patients infected with HIV-1, a virus that causes AIDS, are more susceptible to tuberculosis infection.

“A significant number of people entering Ebola Virus Treatment Units during the 2014-2016 West African outbreak were infected with both the malarial parasites, Plasmodium falciparum, and Ebola virus,” explained Professor Wendy Maury, PhD, the lead investigator at the University of Iowa.

The hypothesis is that people with an acute (active and recent) malarial infection, where the body’s immune response is already ramped up, have a greater chance of surviving Ebola infection. However, if people have chronic malaria, then they are hypothesized to be more susceptible to Ebola.

The researchers will begin by taking white blood cells from infected mice and studying them to determine what role they may play in dual malaria/Ebola infection. Knowing if the hypothesis is supported might change how doctors design therapies for Ebola in areas where both diseases are present, perhaps paving the way for more tailored therapeutics.

SNPRC’S part in the study will be a two-year process. The next step may involve testing in a higher-level animal model, such as nonhuman primates.

Photo credit: National Institute of Allergy and Infectious Diseases

You may want to think twice before sharing a bite of spare food with animals you encounter in public places. That is, unless you’re willing to risk a staph infection.

Staphylococcus aureus (S. aureus) is a bacterium that causes a wide range of infections, such as skin and soft tissue infections (SSTI), bone, joint and implant infections, pneumonia and more. Both penicillin and methicillin have been used to fight S. aureus, but strains resistant to all types of treatment have continued to emerge. Now, methicillin-resistant S. aureus (MRSA) has become a serious international problem.

In a hospital setting, MRSA can be deadly; in fact, it caused 11,000 deaths in hospitals in the U.S. in 2017. And while practices to reduce MRSA cases in hospital populations are improving, the bacterium continues to thrive in the wild in certain geographic areas. It is of particular concern in places where large numbers of humans and animals interact, including popular tourist destinations.

In a recent study, researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) along with their Nepali colleagues sampled 59 rhesus monkeys within Nepal. Those monkeys have close interactions with humans, usually at temple sites, where people offer the animals food. The researchers used a non-invasive method to collect saliva samples from the monkeys with subsequent processing at a microbiology laboratory in Nepal.

The findings were astounding. Of the macaque samples tested, 6.8% were positive for MRSA, and three of four MRSA isolates were identified as ST22 SCCmec IV. The ST22 SCCmec IV strain is normally considered a human strain, and this study suggests that humans in Nepal are sharing their strains with the wild macaque populations.

The researchers further reiterate a warning that is becoming all too well known, that even minimal contact with wild animals, especially contact with saliva or an animal bite can present significant health risks to humans.

“Some types of MRSA are found all over the world and are pandemic strains,” said lead study author Marilyn C. Roberts, PhD. “The importance should be stressed in respect to these populations of wild animals. Even feeding chipmunks or ducks human food is not a good thing. They can pick up what we have, and we can pick up what they have. Some of the infectious agents wildlife carry can be deadly.”

“Given the results of our work in Nepal, we are now extending the MRSA investigation to primates in Thailand. These efforts are part of our larger collaborative program promoting the healthy coexistence between humans and primates,” added co-author and field researcher Randall C. Kyes, PhD.

Photo Credit: Randall C. Kyes, PhD

Sometimes it really does take two. 

Scientists at Yerkes National Primate Research Center (YNPRC) at Emory University in Atlanta have discovered that a form of antibiotic resistance called “heteroresistance” is more widespread than previously thought, but attacking bacteria with combinations of antibiotics may hold the key to defeating them.

“We can think of heteroresistance as bacteria that are ‘half resistant’,” said David Weiss, PhD, director of the Emory Antibiotic Resistance Center, an associate professor of medicine (infectious diseases) and a researcher at the YNPRC. “This is because only some of the cells in the population exhibit resistance. When you take the antibiotic away, the resistant cells go back to being just a small part of the group. That’s why they’re hard to see in the tests that hospitals usually use.”

In exploring the heteroresistance phenomenon, Weiss and his colleagues examined 104 bacterial isolates, tracking multi-drug resistant superbugs. They found more than 85 percent were heteroresistant to at least two antibiotics. Weiss and his team then made their major discovery: Combining two antibiotics to which each superbug was heteroresistant proved effective at killing them. 

This occurred, they found, because the heteroresistant sub-populations were independent. If scientists grew the bacteria in the presence of one antibiotic, or knocked out resistance to that antibiotic genetically, this didn’t affect heteroresistance to any other antibiotics. 

Previously, microbiologists have thought some combinations of antibiotics might work together synergistically — one antibiotic working to weaken one part of the bacteria, while the other hits a different spot. But Weiss indicated the reasons combinations work might largely be explained by heteroresistance to multiple drugs. 

Using this knowledge, scientists are encouraged they will be able to help healthcare professionals more effectively use antibiotics to defeat bacteria that have developed resistance. 

“We’re saying: even if a strain of bacteria is classified as resistant to some antibiotics, don’t toss those drugs in the trash, they may still have some utility,” Weiss explained. “The ones targeting heteroresistance just have to be used in combination with others to do so.”

Tuberculosis is a major concern for HIV/AIDS patients, as a full one-third of all patients with the autoimmune disease die of complications from TB.

But Professor Deepak Kaushal, PhD, of the Southwest National Primate Research Center (SWNPRC) at Texas Biomedical Research Institute, says recent research could help scientists better understand how to prevent this deadly condition.

It’s known the same mechanism of HIV/AIDS which leads to the loss of immune cells (CD4 and T cells) in other parts of the body also targets the lungs, allowing latent Mycobacterium tuberculosis (Mtb) bacteria infection to become active TB. But until now, scientists weren’t sure which parts of the lungs were targeted by the immunodeficiency.

Kaushal and a team of researchers conducted a study on rhesus monkeys infected with TB and SIV (simian immunodeficiency virus), using tissue either from a humanized mouse model or from humans. The findings indicated not all T cells in the lungs are affected by HIV—only the ones embedded inside the lung tissue. T cells in the lung sacs (alveoli) where oxygen enters the blood stream were still functional.

“If our findings are validated in future testing, this leads to the potential for new therapies that would prevent the loss of these crucial T cells during HIV infection,” Kaushal said. “The idea is that fewer HIV patients would progress to TB.”

Kaushal further explained, “[This is] important to know because we can target vaccines, therapeutics and drugs to these specific T cells in the lungs.”

According to the Center for Disease Control and Prevention, more than 1.1 million people in the United States are living with an HIV infection. In the United States, Louisiana has the third-highest rate of people with an HIV infection and AIDS cases. In 2015, Louisiana-based Tulane National Primate Research Center (TNPRC) was awarded $4.2 million to study new ways to flush out and kill HIV from reservoirs in the body where the virus lurks beyond the reach of antiviral therapy options.

Current HIV treatment options can stop the disease from progressing to AIDS and knock the virus down to “undetectable” levels in the bloodstream, but they fall short of an HIV cure because they must be taken for life to keep the disease in check. That’s because HIV integrates into the genome of memory T-cells and lies dormant in reservoirs throughout the body. If a patient stops taking antivirals, HIV reawakens from these reservoirs to resume its attack on the immune system.

“The major obstacle to a cure for HIV infection is how to purge the persistent reservoir of latently infected cells,” said lead researcher Dr. Huanbin Xu, assistant professor of pathology.

Using a nonhuman primate research model of HIV, Dr. Xu plans to test standard antiviral drugs with a combination of therapies to wake up the latent virus and trigger the immune system to recognize infected cells and attack them. He will then target any remaining virus with an antibody drug conjugate, a new class of highly potent biopharmaceutical drugs. The so-called “kick and kill” approach to activate latent HIV so it’s more susceptible to targeted treatments is a promising new frontier in the search for a possible cure, Xu says.

His team will also test a new gene editing approach with a targeted delivery system for the therapy tailored to an individual’s immune system.

“So far, it’s a novel, comprehensive strategy,” Dr. Xu says.

One of the advantages of using a primate research model for the treatment is that, if it’s successful, human clinical trials could begin relatively quickly, Dr. Xu says.

Reviewed: June 2020

What if certain parts of the brain could be turned off to treat neurological disorders like Parkinson’s disease? Though it seems far-fetched now, such a solution could soon become reality.

During the last 10 years, the field of neuroscience research has been revolutionized by new genetic techniques, allowing neuroscientists to express artificial proteins in neurons that can then be modified to study diseases and disorders. One of the most commonly used genetic-based approaches is called chemogenetics.

Chemogenetic techniques use artificial receptor proteins that only become active in the presence of a specific drug. This means only the neurons containing the artificial receptor will change their activity in response to the drug, while other neurons remain unaffected. We can think of it as a chemical switch that turns specific neurons on or off.

While chemogenetics methods have been extensively used in basic research, they have yet to be translated to clinical treatment. However, researchers have recently developed new chemogenetic tools that have the potential to be used in clinical applications. The team, led by Scott Sternson (Howard Hughes Medical Institute’s Janelia Research Campus), included Yerkes National Primate Research Center researchers Adriana Galvan, PhD, and Xing Hu, MD.

In this new chemogenetic system, the researchers activated the artificial receptors by using drugs specifically designed for the receptors, as well as varenicline (Chantix™), an antismoking drug. The receptors and drugs were optimized during in vitro experiments and then successfully used to control the activity of neurons in rodents.

The Yerkes researchers then contributed an important step toward potential clinical application of the tools by duplicating the effects in a nonhuman primate’s brain. When the primate received a low dose of varenicline, the neurons containing the artificial receptors were silenced — all with no observable side effects. The results provide a critical proof of concept that chemogenetic methods can be effectively used in nonhuman primate studies.

Yerkes researchers are now expanding the chemogenetic experiments with the aim of using them in a nonhuman primate model of Parkinson’s disease, which is characterized by some movement-related brain regions being abnormally active. Chemogenetic manipulation could potentially silence or at least modulate the activity of these brain areas and help scientists develop a novel Parkinson’s therapy.

It’s proven stress wears down the body and compromises the immune system—but why?

Scientists can’t yet fully explain how the association between stress and health plays out at the cellular level, but they are closer thanks to recent results from a collaborative study. Researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) in collaboration with researchers at Duke University, the University of Montreal and the Yerkes National Primate Research Center (YNPRC) at Emory University examined the cellular effects of one common stressor: social hierarchy.

“The goal is to understand the mechanisms through which social experiences or environment ‘get under the skin,’ so to speak, to affect health and survival,” said the study’s lead author, Noah Snyder-Mackler, a UW assistant professor of psychology.

In the study, scientists mixed up the existing social groupings of nearly four dozen rhesus macaques at the Yerkes Research Center, observed behaviors among the new groups and analyzed blood samples to determine the cellular effects of the new social order. The team specifically measured effects on the peripheral immune system, which are immune cells that patrol other systems of the body, such as muscles.

Organizing the macaques into novel groups effectively created a new social hierarchy.  The first in the group became the most dominant and held the highest rank, while the last to join the group typically held the lowest status.

After each group’s hierarchy was established and behavior observed, the researchers took blood samples and treated the macaques with a synthetic stress hormone. The results showed the cells of the lower-status macaques were less able to respond productively to the hormone than those of the higher-status animals.

One explanation for this lack of a response was found within the macaques’ immune cells’ genetic information. Low-status females had immune cells that were less accessible to the signal from the hormone. In humans, stressful or traumatic situations have been linked to similar hormonal resistance.

“We know that social adversity early in life can have far-reaching effects that extend into adulthood,” Snyder-Mackler said. “The questions are, when do these events have to occur, how severe do they have to be and are they reversible or even preventable?”

Further research will help the researchers answer these questions, identify the magnitude of the effects of stress and, in the pursuit of improved human health, determine what might protect people from those impacts.

Over the past 150 years, the average onset of puberty has been steadily declining. A century and a half ago, girls reached reproductive competence around 17.5 years of age—but now, the average age is 12.5 years. Early-onset puberty can lead girls to experience health problems later, including increased incidence of ovarian, uterine and breast cancers, as well as being at a higher risk for cardiovascular and metabolic diseases.

Researchers at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) and the Brigham & Women’s Hospital and Harvard Medical School, wondered what was causing this increase in early bloomers. Their research led to the discovery of a new gene (MKRN3) that serves as a “neurobiological brake”, that when mutated advances pubertal development. Children with mutations in the MKRN3 gene show signs of pubertal development as early as 5 years of age. Without this biological pause button, developing kids would be more susceptible to cancer, cardiovascular disease, and metabolic disorders.

“Developing our knowledge of how genes regulate the initiation of puberty will allow us understand why girls are initiating puberty at much earlier ages,” said Dr. Alejandro Lomniczi, lead researcher on the study and assistant professor for the Division of Neuroscience at the ONPRC.

Focusing on the hypothalamus, the ventral part of the brain that controls reproductive development, Lomniczi and colleagues demonstrated that in monkeys and rodents, the MKRN3 gene is highly expressed during infancy and gets shut down right before puberty. Using genetic and biochemical approaches they demonstrated that MKRN3 is a strong repressor of KISS1 and TAC3 gene expression, two strong activators of pubertal development.

With these discoveries guiding their work, researchers are starting to construct the genetic architecture that regulates reproductive development in the brain and one step closer of breaking the “puberty” code.

Updated: June 2020

We’ve all heard the phrase “Mr. Mom” as a descriptor for involved fathers, but men may be more like their female counterparts when it comes to nurturing than we expect.

Most animals are risk-averse and tend to avoid danger, but parents can be a different story. Certain species of mammals will even risk their own lives to save their offspring.

This extreme bond between parent and child has its roots in a biological phenomenon known as “bonding.” When children are born, their mothers experience a rush of hormones designed to facilitate the bonding experience, including oxytocin, estrogen, progesterone and others.

Perhaps the most interesting hormone released during this process is prolactin, which stimulates lactation in new mothers to feed their offspring. It is intriguing not only because of its physical effect on mothers, but because it also appears in (and influences) their mates as well.

Researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin (UW) have discovered male tamarins and marmosets—which live in family units like those of humans—display certain physical characteristics when their respective mates become pregnant.

“The father is critical to the survival of the offspring,” Toni Ziegler, distinguished scientist at the WiNPRC, said of the animals during an interview on a recent BBC Earth podcast.  “And what we know about them from our studies, is the father is picking up on cues from the mother that she’s pregnant. And the father actually starts gaining weight.”

Ziegler noted this is consistent with human males, who frequently report gaining “sympathy weight” when their partners become pregnant.

This discovery could potentially lead to a better understanding of the bonding process and what can be done to nurture the infant-parent relationship from birth into early childhood.