Crib deaths, which claim thousands of lives each year, remain a mystery. Credit: Chris Priest/Photo Researchers, Inc.

International newspapers in September made much of a report showing that a recently discovered virus was present in tissues from a pair of so-called 'crib deaths.' But even the researchers who discovered the virus remain skeptical that it might have caused the deaths.

Doctors initially attributed the deaths of two infant girls in Wisconsin in 2003 to Sudden Infant Death Syndrome (SIDS). But when tissue samples from both infants tested positive for the previously unknown human parechovirus 3 (HPEV-3), the media began speculating about a link between the virus and SIDS.

But Gerald Sedmak, the Milwaukee virologist who first detected the new agent, is unconvinced. “We never made a big deal out of a possible link to SIDS,” says Sedmak. “What we thought was most interesting was that these were the first cases of HPEV-3 in the United States.”

We never made a big deal out of a possible link to SIDS. , Gerald Sedmak, Milwaukee Health Department

HPEV-1, HPEV-2 and the newly discovered HPEV-3 are members of the picornavirus family of single-stranded RNA agents. Parechoviruses have been implicated in flaccid paralysis, encephalitis, gastroenteritis and respiratory infections. Researchers in Aichi, Japan, first reported HPEV-3 in a study published in January (J. Gen. Virol. 85, 391–398; 2004). They isolated the virus from samples taken from a 1-year-old girl with diarrhea, fever and transient paralysis.

But despite HPEV-3's pathogenic profile, there have been no reports of deaths, infant or adult, caused by the virus in Japan, notes lead researcher Miyabi Ito. When the scientists tested children in Aichi for antibodies to HPEV-3, they found that by the time children enter elementary school, more than 80% of them test positive for the virus. “With such a high prevalence and no reported deaths, we considered [the virus] to be very infectious, but relatively benign,” says Ito.

The Milwaukee health department found the virus during a routine screening to track bacterial and viral involvement in unexplained deaths. But viral infection—most commonly by enteroviruses and adenoviruses, cytomegalovirus and influenza—is not uncommon in SIDS deaths, Sedmak notes. “We see about a 30% viral infection rate in SIDS,” he says.

HPEV-3 was not previously on health officials' radar, and questions remain about the route of transmission and the extent of the Milwaukee outbreak. A third case—tissue taken from a 16-month-old whose death was not classified as SIDS—tested positive for HPEV-3 in Milwaukee in August, and confirmation on a fourth is pending. Since 1987, the surveillance program that detected the HPEV-3 infections has also reported 17 infant deaths, including a number of non-SIDS cases, in which HPEV-1 was found in tissue samples, suggesting that the viruses might be relatively common.

Meanwhile, researchers are examining factors ranging from genetic mutations to uterine proteins and the mother's economic status to determine SIDS risk, but have not yet found a single conclusive cause. In the 1990s, SIDS was famously linked to a prone sleeping position, and subsequent national 'Back to Sleep' programs are credited with significantly reducing SIDS deaths. But many infant deaths remain unexplained.

“Some people may feel there's ultimately a single explanatory factor behind SIDS deaths, but most understand it as a catch-all diagnosis for deaths caused by a whole range of undetermined factors,” says Kurt Nolte, a forensic pathologist at the University of New Mexico. “It's one of those things where you just have to keep chipping away.”