DC-Baltimore 2023 Zika Challenge

This page gives a bit more context on the Zika challenge study, the scientific purpose, and the risks and benefits involved for participants. 1Day Sooner is not an official representative of the study and this information does not replace the informed consent process that volunteers will undergo if they decide to sign up for screening. If you do sign up for screening, please let us know — you can email Julia at organizing@1daysooner.org!

About the trial

Why a challenge trial is needed

Risk Faqs

Zika virus and Zika fever 101

The Zika virus (ZIKV) is a virus that causes Zika fever. ZIKV was discovered in 1947. For decades, it was thought to cause at worst a mild illness in humans. Thanks to two major outbreaks — one in French Polynesia in 2014 and the epidemic centering on Brazil from 2015 to 2016 — it became clear that Zika was much more dangerous than previously thought (possibly the result of a mutation). Fetuses in the womb exposed to Zika are at risk of congenital Zika syndrome (CZS), characterized by severe, even fatal, birth defects. Several thousand infants were born in Brazil with CZS as a result of the epidemic, and many died. There is also a rare chance that someone infected with Zika develops Guillain-Barré syndrome (GBS), a neurological disorder. (More on those risks later.)

A group of children with Congenital Zika Syndrome awaiting therapy in Recife, Brazil. Zika fever is very rarely fatal in adults, but can have devastating consequences on fetuses in the womb. (Dado Galdieri for The New York Times, 2022)

Zika fever itself, however, is usually mild, and significantly less deadly than even the flu. According to the CDC, the most common symptoms are fever, rash, headache, joint pain, conjunctivitis (“pink eye”), and muscle pain (CDC). The incubation period is between 3 and 12 days and symptoms generally last about 2–7 days (Pergolizzi et al. 2021).

Zika spread very rapidly during the 2015-2016 epidemic that reached all over the Western hemisphere. Eventually, the epidemic subsided, likely in part due to herd immunity acquired from rapid infections. The consensus among scientists is that another outbreak will likely occur, however, possibly within the next decade or two. As of right now, we are left with no treatments and no vaccines to give pregnant people to protect their unborn babies if an outbreak does occur.

Zika is still circulating in Latin America, but at rates that are too low to enable field studies to test vaccines. That is why challenge studies must be used to line up promising vaccine candidates so that they can be rapidly deployed when the next outbreak occurs.

About the trial

The trial (CIR 316) is run by the Center for Immunization Research at Johns Hopkins University. Participants will be compensated up to $4,875. The trial page includes basic information on eligibility, timeline, and compensation, and links to forms to sign up for pre-screening.

The trial is a human challenge study — a study where volunteers are given a disease on purpose. It sounds a little crazy, but these kinds of studies aren’t rare at all, and have been done safely for dedades among thousands of volunteers for dozens of diseases.

This type of challenge study is called a dosing study (trying to find out the “dosing” of the virus needed to cause reliable infection), so there is no vaccine being tested directly. It’s a prerequisite for any future human challenge trials. The trial could also yield other important information about Zika.

For each cohort, some participants (4 of 14) will be exposed to a placebo instead of the actual Zika virus. All will reside for 9 days in the dedicated CIR facility within the Johns Hopkins Bayview Medical Center. Two cohorts are being run in 2023, and a third will likely begin in early 2024.

Why we need a challenge trial

Zika spread so rapidly during the 2015-2016 epidemic that herd immunity was reached in many areas, which contributed to a huge drop in cases by 2017. That was good news for the world, but eliminated the possibility of conducting useful field trials (Cohen 2018). The virus is still circulating in low levels across South and Central America and the consensus is that Zika will likely return, at the very least as herd immunity in many areas wane. There are also many areas in South and Central America where Zika did not reach and where widespread immune resistance is low (Cohen 2018). If we want to test vaccine candidates to have them ready before the next major outbreak, human challenge studies are necessary.
faq

What are the risks of infection with Zika as part of this trial?

Transmission of Zika to others

Zika is primarily spread through mosquitos when they feed on someone who is infected. The virus in the blood is then transferred to another person if the mosquito bites again. The study will test all participants to make sure no one leaves the inpatient unit while their blood still has Zika virus in it.

However, Zika virus RNA (the genetic material that makes up the virus, like DNA in humans) often remains in semen after the virus itself is eliminated. This is most common in the first month or so after infection, and drastically decreases as time goes on, but in rare cases may remain for more than half a year (Mead et al. 2018.) The study team will discuss risks of transmission with participants, including the measures needed to protect against these risks, such as the use of barrier contraception (condoms) for 90 days after infection.

Getting Zika fever (risk: high)

The primary risk of infection by the Zika virus is coming down with symptoms of Zika fever. In the wild, this happens in about 20% of infections (Haby, Pinart, Elias, Reveiz 2018), but in the previous cohorts for this challenge study, almost everyone who was challenged with Zika had symptoms. The most common symptoms were rash (95%) and joint pain (65%) (Lenharo 2023). 10 of the 14 people in each cohort of the trial will be exposed to Zika. The other four will be injected with a placebo.

In addition to rash and joint paint, a systematic review article in 2021 gave the following as the most common symptoms of Zika fever in the wild (Halani et al. 2021):

  • Fever, 62%
  • Conjunctivitis (“pink eye,” inflammation of the eye), 45%
  • Myalgia (muscle pain), 48%
  • Headache, 46%
  • Diarrhea, 13%

Death from Zika fever (risk: extremely low)

As with virtually all diseases, death is possible, but for Zika fever this is very, very rare in healthy adults. Data collected by the Pan American Health Organization from August 2016 to January 2018 included 20 deaths directly attributed to Zika fever out of a total of 583,451 suspected cases — about 3.4 deaths per 100,000 cases ( PAHO). A systematic review in 2021 found a case fatality rate of 2.3 per 100,000, and a 2019 systematic review found a rate of 2.0 per 100,000. The majority of deaths occurred in the elderly or those with significant comorbidities (Puntasecca, King & LaBeaud 2021;Ospina et al. 2019).

For comparison, the CDC estimated that as a result of the 2019-2020 influenza season in the US, there were 36 million symptomatic cases and about 25,000 deaths — about 69.4 deaths per 100,000 cases (CDC 2020). Direct comparisons between these diseases are imperfect, and true rates of death are very difficult to measure because of how many undetected, asymptomatic cases there may be, but this still shows that the risk of death from Zika fever is extremely low.

Note that below we also discuss the risk of other neurological conditions, which also carry the risk of death or other severe outcomes.

Guillain-Barré Syndrome (risk: very low)

In some places, there has been evidence of connection between infection with Zika virus and later development of a neurological condition called Guillain‒Barré Syndrome (GBS). Guillain‒Barré Syndrome is characterized by the body’s immune system attacking nerve cells, which leads to symptoms like muscle weakness and in severe cases, inability to walk unassisted or even full paralysis and death. For Zika-related GBS, the primary symptoms are paralysis in the arms and legs, and facial palsy (weakness of face muscles) (Leonhard et al. 2020).

There is no definitive probability of the risk of Guillain‒Barré Syndrome for a person infected with Zika virus. A 2018 comprehensive review of previous outbreaks suggested that there are about 2 cases for every 10,000 Zika infections; this risk was found to be lower in females and higher with age, especially for those over the age of 40 (Romero, Delorey, Sjevar & Johansson 2018). Noticeable GBS symptoms typically developed between 5 and 12 days after Zika infection symptoms appear (Leonhard et al. 2020).

Most people recover from GBS, even in severe cases, though it may persist for months or longer. A systematic review in 2020 found that approximately one-fifth of those with Zika-linked GBS required intensive care, including mechanical ventilation, and that the death rate was 4.6% (22 deaths out of 475 cases) (Leonhard et al. 20208).

Other neurological issues (risk: very, very low)

Zika infection has also been associated with cases of other neurological disorders besides GBS, primarily transverse myelitis (Oligbu et al. 2018) and meningoencephalitis (Pradhan et al. 2017). These conditions affecting the central nervous system can be serious, but are extremely rare, and appear to occur even less frequently than Guillain-Barré Syndrome.

Fetal Congenital Zika Syndrome (CZS) (risk: very low)

This arm of the study is only enrolling males (i.e. people born without a uterus, regardless of gender identity.) Participants will be required to use contraception in the months after they are released from inpatient. If proper precautions are not taken, Zika cannot be transmitted.

Approximately 7% of fetuses of people with symptomatic Zika infections during pregnancy are born with CZS (Hoen et al. 2018). This rate appears similar to those with asymptomatic infections (Honein et al. 2017). The mortality rate of infants born with CZS in one study was 11.3 times higher than non-CZS infants (Paixao et al. 2020).

Later severe Dengue fever (risk: very low)

It is possible that prior infection with Zika might make later infection with Dengue fever more severe. Dengue virus is related to Zika virus and likewise usually causes mild sickness, but it can be fatal. With proper medical treatment, fatality is usually under 1% (WHO 2022). Dengue can be found throughout the tropics, including very occasionally in southern parts of the United States; in the last ten years, there have been small outbreaks in Hawaii, Florida, and Texas (CDC).

Evidence of increased severity of Dengue after a Zika infection is not conclusive, but it is possible, based on scientists’ understanding of how the body reacts to viruses in the Dengue and Zika family (flaviviruses). Additionally, one study of 302 children in Nicaragua who contracted dengue fever showed that those who had previously had Zika were more likely to experience symptoms. They were also more likely to experience severe Dengue (5.9% versus 0.7% for children who had not had Zika or Dengue before). There were no deaths in the study (Katzelnick et al. 2020).

Risks to future pregnancy (extremely low/none)

The US CDC states: "Current evidence suggests that Zika infection prior to pregnancy would not pose a risk of birth defects to a future pregnancy." (CDC 2022) Zika harms the fetus by infecting nervous system cells and causing cell death during crucial stages of development (Paixao et al. 2020). Zika RNA can be detected in some bodily fluids for several weeks after infection, however. The CDC recommends waiting two months post-infection before trying to become pregnant (CDC 2019) and the UK NHS recommends waiting three months (NHS). The study will periodically measure Zika levels in participants’ bodies for several months after infection.