Over 230 people get puzzling neurological disorder in Peru; emergency declared

Over 230 people in Peru have developed a rare, paralyzing neurological disorder called Guillain-Barré Syndrome, leading government officials to declare a national emergency and the World Health Organization to send out a disease outbreak alert.

So far, four people have died from the disorder, which involves the immune system attacking peripheral nerves. It often starts with progressive muscle weakness and numbness that can lead to paralysis and, in about a quarter of the cases, the need for mechanical ventilation.

Peru—a country of over 34 million people—typically sees fewer than 20 suspected cases per month of Guillain-Barré Syndrome (pronounced ghee-yan bar-ray or abbreviated GBS). But, between June 10 and July 15, the country tallied 130 cases, including the four deaths, bringing the year's total to 231, the WHO reported Tuesday.

The cases are widely distributed throughout the country, with 20 of the country's 24 governmental regions (departments) reporting at least one case. Seven departments have reported high numbers—including Lima, at the central coast, to Piura and Lambayeque in the far north, and Cusco, which is southeast of Lima. But no other countries in the Americas report an uptick in GBS cases.

The cause of the outbreak is puzzling—even though this isn't Peru's first alarming GBS outbreak. In 2019, the country reported an unprecedented surge of nearly 700 cases between May and July, bringing the total to over 900. Before that, a large GBS outbreak was considered between 30 to 50 cases.

Researchers concluded that the culprit behind the extremely unusual 2019 outbreak was the intestinal pathogen, Campylobacter jejuni. The gut-dwelling bacteria is well-known as one of the most common causes of food poisoning and diarrheal cases in the world. But, less well-known, it's also one of the leading triggers for GBS.

Unusual suspect

There are hints that C. jejuni is again the cause of the GBS outbreak in Peru. Of 22 clinical samples taken from Peruvian patients between June and July, 14 (63 percent) were positive for the gut microbe. But, even if C. jejuni is behind the current outbreak, there are still a lot of unanswered questions—including how it's spreading.

In a 2020 report, researchers from the US Centers for Disease Control and Prevention, Peru's CDC, and Peru's national health institute wrote findings from their investigation of the outbreak. They noted that the C. jejuni isolates were highly related, and the cases rapidly increased and then decreased, suggesting a "point-source exposure." But just like in the current outbreak, the cases were spread across geographically disparate regions, making a single source unlikely.

"Because of the wide distribution of outbreaks in many geographically separated regions, we questioned how all areas were exposed to C. jejuni within a short time frame," they wrote. And they left the question lingering.

Also puzzling is why some people develop GBS and others don't. In general, GBS is an autoimmune disease most often thought to be triggered by an infectious disease. C. jejuni is behind about a third of cases, but Mycoplasma pneumoniae, cytomegalovirus (CMV), and Zika virus area also known triggers. In very rare instances, vaccines have also provoked GBS.

In the case of C. jejuni, the microbe carries an unusual coating of lipo-oligosaccharides (LOSs), some of which seem be molecular mimics of normal components of human nerves—specifically, their myelin sheaths (the insulating layer around nerves) or the axolemma (the cell membrane around a branch of a neuron that transmits signals (axon)). When the immune system tries to fight off a C. jejuni infection, it may mistakenly direct the attack to nerves' myelin sheaths or the axons of motor never cells. This leads to different subtypes of GBS called: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), respectively.

Lingering questions

There are nearly 50 serotypes of C. jejuni and 23 classes of LOSs that coat them, helping to explain why the common cause of gastroenteritis only rarely causes GBS. It also helps explain Peru's 2019 outbreak. In a study published in 2022, researchers in Lima examined 71 C. jejuni strains isolated from the 2019 outbreak, finding that they had LOS genes associated with molecular mimicry of human nerve cell components. That study also found that the outbreak strains (belonging to the ST-2993 designation) are closely related to strains found in chickens, suggesting that chickens could be a reservoir for this particular dangerous variety of bacteria.

But the information isn't enough to fully explain the GBS cases. Another study, published in 2021 and led by researchers in Lima and at Johns Hopkins University in the US, collected clinical data from 49 GBS patients from the 2019 outbreak. They noted that while signs of a recent C. jejuni infection was common among GBS cases, it was also fairly common among a set of controls who didn't have GBS—55 percent compared with 27 percent. This "may be indicative of an ongoing outbreak of C jejuni, although our study was not designed to investigate this," they wrote. Additionally, 27 percent of the GBS cases that reported diarrhea didn't have signs of a C. jejuni infection, suggesting they may have been infected with some other gut pathogen.

The data feeds into open questions about why some are struck with GBS while others are spared. Researchers speculate that various factors may come into play, including genetic variation in each individual's immune responses, the ability of individual microbes to vary their surface antigens (a phenomenon called phase variation), and the variability of the strength of antibodies that the immune system directs. There's also some suggestion that a single pathogen may not be the sole trigger for GBS, but co-infections play a role.

For now, the WHO calls on countries to continue monitoring for GBS and raise awareness among health care systems. There is no cure for the disorder, but treatment can ease symptoms and hasten recovery. Most people will recover fully from GBS, even in the most severe cases, but full recovery for some can take months to years.