April 8, 2022 -- Every day we see stark images of the war in Ukraine: bombed-out buildings, explosions, and bodies lying in the streets.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally.

But there's another, less visible war — against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here's what Ukrainians — and their neighbors — are facing on the infectious disease front.

Andrey Zinchuk, MD, a critical care doctor at Yale who was born in Ukraine and immigrated to the US at the age of 14 with his family, says that tuberculosis and HIV rates in Ukraine have long been especially high, even before the current conflict.

"Part of the challenge of the healthcare system in Ukraine is that it's difficult to maintain a steady policy because of political instability," he says. "We've had three revolutions in the last 20 years," not counting the current Russian invasion.

The first upheaval was the breakup of the Soviet Union, which led to "an epidemic of people with HIV, hepatitis, and opioid use," he says.

Next was the Orange Revolution in 2004 over fraud during a presidential election.

In 2014 came the Maidan Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia, and Russia annexed Crimea.

"There was essentially infiltration in Russian propaganda in the east of the country," Zinchuk says. "This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People's Republics) which were mostly Russian-speaking parts of the country," an area known as the Donbas. This resulted in a war in eastern Ukraine that began in 2014, with more than 10,000 deaths.

After the 2014 revolution, Zinchuk says, "there was a tremendous change in the way…medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions."

Spending on healthcare in Ukraine has still been quite low. Even before the current conflict, Zinchuk notes, annual healthcare spending in Ukraine was about $600 per person. In comparison, it's about $4500 per person in Germany and $12,530 in the United States.

Despite low spending, access to medicines such as insulin for diabetes and antibiotics for tuberculosis was stable before the war. But now, Zinchuk says, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have "no plumbing and have to heat the house by burning firewood." More significantly, their supply of medicine is unstable.

Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, says diarrheal diseases, especially in kids, are of most immediate concern.

“The water supply [of Mariupol] is no longer potable, but people are drinking it anyway,” he says. “Sewage systems are destroyed, and raw sewage is just released into the rivers and streams.”

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps.

Respiratory Infections

Although not as high on the list of concerns as tuberculosis or HIV, COVID-19 remains a big problem for infectious disease experts.

Last fall, Ukraine ranked just behind the US and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial set of vaccinations.

The same conditions that fuel tuberculosis and COVID — crowding, especially in poorly ventilated settings — could lead to a measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases.

Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of tuberculosis cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis — 27%. The country also has the second-highest rate of infection with both tuberculosis and HIV (26%) even before the war.

Experts say war is a perfect breeding ground for tuberculosis, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in tuberculosis diagnosis and treatment in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end tuberculosis by more than a decade.

Drug-resistant tuberculosis has been one of the biggest worries. In their report on tuberculosis in Ukraine, British experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that "drug resistance thrives on fractured health systems and sporadic medicine supply."

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, "[If] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease, but multidrug-resistant tuberculosis disease," and patients could become infectious again.

Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he says that he's impressed at the Polish government's efforts to ensure care.

Especially with the triad of HIV, tuberculosis, and opioid use, Wingfield and Potter emphasized that these problems reflect the social determinants of health — "the experiences and conditions in which people live." These medical conditions are all quite treatable with support, and once treated they pose no risk to others.

HIV and Opioid Use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world — 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

"When Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it's illegal in Russia to use buprenorphine or methadone,” Yale’s Vermund says. “So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin."

Altice says that of 800 patients in the region who had to go cold turkey, "10% were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress."

And as they relapsed, the HIV rate soared. "50% of the methadone patients have got HIV," Altice says. "If they stop taking the methadone, they're going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized."

This experience may soon repeat itself. There were two methadone factories in Ukraine — in Odessa and Kharkiv — that are now shut down by the war.

Although there are efforts to import methadone and many other drugs, supply chain issues are "devastating," Altice says.

"[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they'll be desperate,” he says. “So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves," and he predicts an explosion in HIV.

Altice says that with the immigration to Poland and the west, many Ukrainian refugees "are relying on the kindness of strangers." They are likely to be "fearful to disclose either their HIV or their tuberculosis treatment status," being afraid of being regarded as modern-day lepers, even though they are likely not infectious.

Both Altice and Potter say the governments of Poland and other receiving countries need to provide the refugees with "reassurance that their health information will not be shared with others."

Potter says that extraordinary care needs to be taken, so that shared information is not used for deportation.

When refugees are housed with hosts living in rural areas, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with tuberculosis, HIV, and addiction who are placed in rural locations may have difficulty getting to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, says that a network of European tuberculosis researchers have developed a database where patients with tuberculosis can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

Waterborne Infections

In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern.

In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound Infections and Antimicrobial Resistance

The ECDC also reports high rates of antimicrobial resistance in Ukraine, particularly involving common bacteria including E. coli.

Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for drug-resistant pathogens. These infections often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. The World Health Organization has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active campaign against COVID vaccines in Ukraine, while at the same time advocating vaccines in Russia.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.