UF professor uses mathematical models to explain viral dynamics and drug resistance.

There are six major genotypes of Hepatitis C infections. In the U.S., 70 percent of cases are caused by genotype 1. In an infected person, about 1012 virus particles are produced each day. There is no vaccine, but chronic infection can be cured 95 percent of the time with new anti-viral medications. Having so many numbers to wrangle, UF applied mathematician Libin Rong is eager to tackle the problems facing healthcare providers, pharmaceutical developers, and epidemiologists. How quickly do viruses reproduce, and how does that rate change after drug treatment? How much drug treatment is needed to be effective?

Rong was born in a small village in China, where he became interested in math at a young age. He went to college in Shanghai to study pure mathematics, but he soon delved into the applied realm by modeling neural networks for artificial intelligence. In a postdoc position in mathematical biology at Los Alamos National Laboratory, he shifted further toward a fusion of the natural and mathematical sciences. Intrigued by the many collaborative opportunities at UF, he left his previous position at Oakland University to join UF’s Department of Mathematics and work with researchers at UF’s College of Medicine and the Emerging Pathogens Institute. He also is thrilled to have a large pool of graduate students from which to choose as his mentees. “I enjoy supervising students,” he says.

man standing in front of chalkboard
Libin Rong

Rong develops mathematical models to predict the numbers of diseases at each point: spread among a population, infection and onset of symptoms, response to drugs, and emergence of drug resistance. “We use differential equation systems to describe a biological process, then we compare the modeling projection with the real data” — which he obtains from colleagues in health sciences — “so that we can determine or test different mechanisms underlying those biological data. We can also quantify the drug effectiveness,” he says.

Recently, Rong has been focusing on Hepatitis C. “A lot of drugs have become available, but the virus can mutate, and if a drug is used as a mono-therapy — if we just use one drug — drug resistance can emerge very quickly,” says Rong. “I developed a mathematical model to explain why drug resistance is expected so rapidly after the mono-therapy, and then to estimate how many drugs would be needed to overcome the resistance.” Currently, he is collaborating with researchers at UF’s medical school to determine which combination of drugs is an optimal therapy for Hepatitis C. He also is looking at how Hepatitis C treatments might apply to Chikungunya, a mosquito-borne disease with no approved drug therapies.

Rong’s other primary focus is HIV. Particular characteristics of HIV make its eradication challenging. In particular, latent reservoirs of the virus can reemerge after years of treatment, even after the initial dormancy period. “We don’t know why this pool is so stable even after continuous therapy for many years,” he says. Patients experience “blips,” or temporary surges in the viral load (the amount of virus in the blood). Whether the blip is just a blip, or a sign of failing treatment or drug resistance, can be addressed through mathematical modeling. “We proposed a few mechanisms to try to explain this blip and the stability of the latent reservoir, and we have one mechanism confirmed by data,” Rong says. With continued collaborations among UF’s colleges, Rong hopes that a solution can be found.

UF researcher Calistus Ngonghala uses math to understand the spread — and prevention — of disease in sub-Saharan Africa.

By Terri Peterson

For UF mathematical biology professor Calistus Ngonghala, researching the relationship between poverty and disease is more than an academic endeavor. Ngonghala grew up in rural Cameroon in central Africa in the 1980s, with friends and family living a subsistence lifestyle. He witnessed the devastating social impact infectious diseases such as HIV and malaria can inflict, recognizing that disease and poverty can reinforce one another and force a community into a poverty trap.

“If you were sick, you walked many miles or squeezed into a compact car to ride ill-kept roads to see a doctor, or suffered with the illness,” says Ngonghala. All of these options degrade an individual’s ability to support oneself, whether due to the incursion of medical expenses, or by lost work time and attendant lost wages. In turn, this degradation exacerbates the problems of poverty, creating a deeper trap from which to climb. “I knew this was the problem I wanted to solve when I left for college. It’s grown up inside me.”

Ngonghala points out that not all poverty is the same, and not all relief efforts achieve desired goals. “We can apply a patch to a poverty-stricken area. For example, we can send in food. And that might be what one community needs to survive, but another area may be in need of something else, like medical supplies. There’s no one Band-aid that works everywhere.” Also, one-time relief efforts might work for some cases, but can be problematic in other situations. For example, sending food to an area enduring persistent extreme poverty may temporarily elevate an individual’s well-being within that state of poverty, but it won’t eliminate it. Eventually, the food is eaten or the supplies are depleted, and the relief recipient is back to square one.

In order for relief efforts to be considered a “sustainable good,” they require coordination of resources and oversight. While this may sound like an enormous task, Ngonghala points to the east African country Rwanda as an example of poverty, disease, and recovery. After the brutal Rwandan genocide in 1994, the country descended into extreme poverty. Minimal resources were available, human capital was unskilled, and most of the population was undernourished and demoralized. The Rwandan government used its relief funds to strategically implement systemic overall changes, initially providing broad access to health care. Healthier people made for more efficient workers more readily able to contribute to the economy. Today, Rwanda is growing in health, education and income, with disease rates that have dropped by as much as 80 percent and a life span that has doubled.

To allow other communities or countries to experience this sort of recovery, Ngonghala has built and is testing a mathematical framework that can be modified to accommodate a wide range of environments and positively impact future policy measures. “Initially we think of the extreme examples of poverty, where many people are unhealthy and have limited access to food, water and other basic resources. But poverty is also a problem in wealthy countries, even if much of the population is generally healthy. Once the framework is ready, we plan to take this to every government that will listen.”

Liberal Arts and Sciences investigators at UF’s Emerging Pathogens Institute are here to rid the world of dangerous microbes, wielding state-of-the-art technology with their scientific toolkits of electronic tracking, computer analysis, and petri dishes!

The Geographers:

Professors Gregory Glass and Jason K. Blackburn use telemetry, remote image sensing, and geographic information services data to predict outbreaks of non-viral pathogens.

Gregory Glass
Gregory Glass
Jason Blackburn
Jason Blackburn

MALARIA

Protozoan. Common throughout tropical and subtropical regions worldwide. Around 200 million cases annually. Mortality rate varies widely depending on location, comorbidity, and demographic.

Glass uses spatial and climate data to study environmental changes that affect the populations of animals, ticks, and mosquitoes in Florida and around the world. He also collects data on blood testing, insecticides, and other intervention measures to examine their effectiveness.

ANTHRAX

Bacterium. Common throughout Central and South America and southern Europe. 2,000 cases annually. Threat of weaponization. Mortality rate for intestinal infections is 25 to 75 percent; for respiratory, 50 to 80 percent.

Blackburn directs the Spatial Epidemiology & Ecology Research Lab (SEER Lab) and studies how Bacillus anthracis causes anthrax outbreaks among wildlife, livestock, and humans by modeling the pathogen’s ecological niche and transmission mechanisms. To do so, SEER Lab combines GPS technology to track animals, such as elk and bison, and laboratory work to study environmental conditions that promote B. anthracis spore persistence. Blackburn works with UF ecologists Jose Miguel Ponciano and Robert Holt in an NIH-funded project to study environmental reservoirs and anthrax transmission.

The Biologists:

Professor Derek Cummings and research assistant Kyra Grantz use statistical analysis of sociodemographic data to monitor and predict the spread of disease.

Derek Cummings
Derek Cummings
Kyra Grantz
Kyra Grantz

DENGUE

Flavivirus. Endemic to Puerto Rico, common throughout Latin America and Southeast Asia. 50 – 528 million cases annually. Mortality rate is 1 percent.

Cummings has worked on risk models of the new dengue vaccine, called CYD-TDV and trademarked Dengvaxia. People experiencing their second natural dengue infection have a higher risk of severe symptoms than those with their first infection. After two infections, however, the risk of severity decreases. Because the vaccine imitates a natural infection, it works best in areas where people have already been exposed to the virus. Given the dangers associated with vaccinating someone who has never been exposed to dengue virus, Cummings recommends a point-of-care screening tool that could identify those who have been infected in the past.

INFLUENZA

RNA virus. Worldwide, occurs in annual outbreaks, with rare pandemics. 3 to 5 million cases annually. Mortality rate is 1.5 percent.

In 1918, an unusually deadly flu swept the world, claiming 50 to 100 million lives in a pandemic often called the Spanish flu. Grantz studies how sociodemographic markers and urban infrastructure affected the spread of the flu in Chicago in that terrifying year. Analyzing 100-year-old data collected by the U.S. Census and the Chicago Department of Health, she’s found that mortality rates increased with illiteracy and unemployment and decreased with homeownership. She developed a technique to model the spread of infectious disease and found that increased likelihood of mortality can be determined on a meter-by-meter basis. This finding suggests that neighborhood-level outbreaks are a vulnerable point in epidemic control.

– by Rachel Wayne

UF’s Emerging Pathogens Institute (EPI) is on the front lines of defense against Zika, which has traveled through Central America into the United States, with the first Florida cases in July 2016. EPI researchers include UF biology professor Derek Cummings, who with research assistant Kyra Grantz collaborated on an international project studying the genetics of the Zika virus, and geography professor Sadie Ryan, who studies the ecology of the mosquitoes that transmit Zika. Following is a shortlist of what we know about Zika, with crucial input from EPI.

  1. Zika is not a new species, but it is new to the Americas and is becoming endemic to Central and South America. Its origins are in the Zika forest of Uganda.
  2. Zika is a flavivirus, related to dengue and West Nile. Flaviviruses are typically spread through a vector, i.e. an uninfected species that transmits the virus from one host to another, usually mosquitoes, ticks, or other blood-sucking arthropods.
  3. Flaviviruses may make infected people more susceptible to other flaviviruses or worsen their symptoms and side effects.
  4. Flaviviruses often cause brain and nerve complications. Zika shows few symptoms in the infected, but raises the risk for Guillian-Barre syndrome, a neurological disease, by 10 times.
  5. Pregnant women infected with Zika may pass it on to their fetuses, causing microcephaly at a risk rate of 20 to 30 percent. Microcephaly is the only birth defect caused by a mosquito-borne disease and is characterized by an undersized brain, usually accompanied by poor motor function and speech, seizures, and intellectual disability. There is no cure.
  6. Only one in five infected people will experience symptoms, which may include rash, joint pain and body ache, headache, conjunctivitis and eye pain, vomiting, and mild fever. People with these symptoms who have recently traveled to Central and South America or have been in intimate contact with someone who has should seek medical assistance.
  7. Zika may be spread among humans through sexual contact, and it can survive in semen for six months. Both strains of Zika may spread among non-human primates and may be passed from non-human primates to humans. There is no evidence that other animal groups (e.g. cats and dogs) may pass Zika to humans.
  8. Urbanization and globalization are major factors in pandemics, as mosquito breeding grounds multiply and people travel over greater distances. Removal of standing water, wearing of protective clothing, and regular use of insect repellant are the best methods of personal protection.
  9. Zika is spread by females of two species of mosquitoes:
  10. Aedes aegypti and Aedes albopictus. A. aegypti is the primary vector and easily breeds in water-storage containers of any kind.
  11. As of press time, there are 3,951 travel-related cases in US; in Florida, 708 travel-related cases and 139 locally acquired cases.

Visit the Miami Herald’s Daily Zika Tracker