H5N1

Colombia: Microcephaly update, week 13

The National Institute of Health has published its Boletín Epidemiológico for week 13. In that week, eight new cases of microcephaly and other congenital central nervous system defects have been reported. Between week 1 of 2016 and week 13 of 2017, 137 Zika-associated cases of microcephaly and congenital CNS defects have been confirmed. This is an increase of one over week 12. Another 342 suspected cases have been discarded, and 556 are under study.

Vital Signs: Update on Zika virus–associated birth defects and evaluation of all US infants with congenital Zika virus exposure

Via MMWR: Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016. The abstract: 

Background: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants.  

Methods: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. 

Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations.  

Results: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus–associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%–7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%–14%]). 

Birth defects were reported in 15% (95% CI = 8%–26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%).  

Conclusions and Implications for Public Health Practice: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. 

Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

A clue to the mystery of Colombia’s missing Zika cases

Via Wired.com: A Clue to the Mystery of Colombia’s Missing Zika Cases. Excerpt:

In December of 2015, Magdalena Sanz Cortes was seeing patients at Texas Children’s Hospital and teaching classes in the ob-gyn department at the Baylor College of Medicine, when she got a call from Barranquilla, Colombia. Miguel Parra Saavedra, a gynecologist in the coastal metropolis, was worried by all the patients coming to his office showing signs of the mysterious Zika virus that had hit Brazil less than a year before. 

Alarming reports of microcephaly—abnormally small heads and brain damage caused by the Zika virus—were beginning to come out of Colombia’s neighbor to the east. Sanz Cortes and Parra Saavedra decided to start monitoring Barranquilla’s pregnancies to see if a similar wave would hit Colombia. 

It never did.  

In Brazil, more than 2,300 Zika-infected babies have been born with microcephaly since 2015. In Colombia, the world’s second largest outbreak has produced far fewer: only 82. Taking total population into account, that’s still more than an order of magnitude less. The disparity has bewildered public health officials, and caused many to question the link between the birth defect and Zika. 

The US Centers for Disease Control formally declared a causal link between microcephaly and the virus in April of 2016, citing a compelling accumulation of data from Brazil, including finding Zika virus in the brain tissue of affected infants. But Colombia’s microcephaly cases never materialized. 

By collecting detailed brain images of more than 200 developing fetuses from expecting mothers along the Colombian Caribbean coast, Sanz Cortes and Parra Saavedra think they have found something close to an explanation: Microcephaly wasn’t appearing in just a few cases, it was appearing in just the worst cases. Zika was still causing significant brain damage even in babies without below average-sized skulls.  

“We now suspect that microcephaly is just the end of the spectrum,” says Sanz Cortez, who presented the results of her team’s study at a meeting of the Society for Maternal-Fetal Medicine on Friday. “But the brain tissue stops growing well before that.” 

What this means for doctors, she says, is that simple head measurements are not enough to make a diagnosis for the suite of developmental defects caused by the virus—sometimes called congenital Zika syndrome. Physicians should also be using ultrasound and fetal MRIs to identify less obvious signs of infection. 

While early detection won’t change outcomes—doctors still don’t have a treatment for the disease’s congenital effects—it’s important for expectant mothers to mentally and emotionally prepare for the challenges ahead. Especially if those challenges aren’t obvious in the delivery room. 

Despite the fact that those results haven’t yet been peer-reviewed, they do match up with another recent study from a group of researchers in Seattle and Brazil who reported on 13 Zika-infected infants born with normal-sized heads. As they got older, these children began to develop new complications. Their heads didn’t grow as fast as the rest of their bodies; they had strange muscle weaknesses and spasms. MRIs showed that inside their skulls they had similar symptoms to the Colombian babies—decreased brain volume, too much fluid in certain brain tissues. 

That means there may be a lot of babies out there who have yet to show signs of congenital Zika defects. And if brain scans don’t expose them, time will.

Emergence of epidemic Zika virus transmission and congenital Zika syndrome: Are recently evolved traits to blame?

Via mBio: Emergence of Epidemic Zika Virus Transmission and Congenital Zika Syndrome: Are Recently Evolved Traits to Blame? The abstract:

The mechanisms responsible for the dramatic emergence of Zika virus (ZIKV), accompanied by congenital Zika syndrome and Guillain-Barré syndrome (GBS), remain unclear. However, two hypotheses are prominent: (i) evolution for enhanced urban transmission via adaptation to mosquito vectors, or for enhanced human infection to increase amplification, or (ii) the stochastic introduction of ZIKV into large, naive human populations in regions with abundant Aedes aegypti populations, leading to enough rare, severe infection outcomes for their first recognition. 

Advances in animal models for human infection combined with improvements in serodiagnostics, better surveillance, and reverse genetic approaches should provide more conclusive evidence of whether mosquito transmission or human pathogenesis changed coincidentally with emergence in the South Pacific and the Americas. 

Ultimately, understanding the mechanisms of epidemic ZIKV emergence, and its associated syndromes, is critical to predict future risks as well as to target surveillance and control measures in key locations.

Colombia: Zika-related microcephaly cases update, week 52

The National Institute of Health has published its Boletín Epidemiológico for week 52. On page 117, it reports 77 confirmed cases of Zika-related microcephaly and other congenital central nervous system defects. This is an increase of five since week 51. In addition, 183 cases were discarded, 62 were neither microcephaly nor congenital defect, and 583 cases are under study. 

JAMA: Preliminary results from the US Zika Pregnancy Registry

Via JAMA, an editorial: Preliminary Results From the US Zika Pregnancy Registry | Congenital Defects. Excerpt:

Human illness caused by Zika virus infection has been described for several decades, but this pathogen was in a sense better classified as an infectious diseases “trivia question” before reports of larger outbreaks appeared within the last 10 years. Nonspecific symptoms of viral infection, including fever, rash, arthralgia, and conjunctivitis, have been described for Zika infection, and asymptomatic infection is fairly common. However, now that strong and accumulating evidence has implicated Zika infection during pregnancy in severe central nervous system sequelae after infection of the fetus, there has been increased urgency in acquiring a greater understanding of the pathophysiology of Zika disease, and efforts to control the spread of this virus have escalated. 

Among the many unanswered questions associated with Zika virus infection during pregnancy is whether the risk of congenital abnormalities is influenced by the gestational timing of maternal infection (early vs late). There is precedence with other congenital infections to anticipate that infection early in pregnancy will lead to greater risk of severe adverse neurodevelopmental outcomes. 

Congenital rubella syndrome, characterized by a variety of clinical features, including central nervous system, ocular, auditory, and cardiac effects, is well described as having a substantially increased risk of fetal infection when maternal infection is acquired early in pregnancy, with few clinical manifestations when maternal infection occurs after 20 weeks’ gestation. For cytomegalovirus, primary maternal infection is less likely to transmit the virus to the fetus early in pregnancy. 

However, if fetal infection does occur, the risk of severe, often neurologic birth defects is higher when transmission occurs earlier in pregnancy. Whether the timing of infection affects the risk of congenital abnormalities is critically important for families, physicians, and the development of public health approaches to screening.  

The report from Honein et al. in this issue of JAMA provides important preliminary data from the US Zika Pregnancy Registry (USZPR), a surveillance system organized by the Centers for Disease Control and Prevention (CDC) to track pregnancy and fetal/infant outcomes after maternal exposure to Zika virus. 

The authors report that among 442 completed pregnancies among women with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 fetuses/infants, including 22 (85%) with brain abnormalities with or without microcephaly. Infants born to mothers in whom infection likely occurred in the periconceptional period or first trimester (9 cases) or in multiple trimesters including the first trimester (15 cases) had a higher risk of birth defects than in cases in which the exposure was later in pregnancy (11% vs 0%). None of the clinically examined anomalies were identified in infants born to mothers when evidence of Zika infection was only within the second or third trimesters of pregnancy. 

These data are important because they represent the outcomes associated with maternal Zika infection among US women, although the exposures to the virus occurred in countries with active Zika transmission rather than in the United States.

How dangerous is Zika for babies?

Via NPR's Goats and Soda blog: How Dangerous Is Zika For Babies? Scientists Try To Figure Out The Answer.

So far, the only region reporting a large number of microcephaly cases is the northeastern tip of Brazil, Nielsen says. Brazil has reported about 2,200 cases in total. And nearly 1,700 have occurred in the northeast region, the Ministry of Health reported.  

But other countries have reported many fewer. Colombia is second highest with about 70 cases. The U.S. is third with 37. Then the Dominican Republic with 22 and Guatemala with 15. One way to think about this data is that Brazil has about four times the number of people as Colombia but about 30 times the number of Zika cases. 

Right now, no one is sure why the northeastern part of Brazil has been hit so hard with microcephaly cases.  

"What I personally believed happened in this region is that the attack rate — meaning how many people got infected with Zika — was extremely high," [Dr. Karin] Nielsen says. 

Another hypothesis is that some environmental factor, such as pesticide exposure or being infected at the same time with another virus, could have increased the risk of microcephaly in northeastern Brazil.  

And indeed, infection with another mosquito-borne virus, called chikungunya, can cause miscarriages and low birth weights. But so far, there's been no evidence that this virus increases the risk of birth defects, Nielsen says. 

OK, so that's the good news — the risk of microcephaly isn't has high as health officials first feared. And case numbers across Latin America and the Caribbean have been low, so far. So what about the bad news? 

Several studies have found that the effects of Zika on a developing fetus go way beyond microcephaly. Now, it looks like these Zika-related problems may be vastly more common than previously predicted.  

"There's been tremendous focus on microcephaly," Nielsen says. "I think it's wrong to focus on microcephaly because most studies have actually shown that microcephaly is not the most common problem with Zika." 

Nielsen and her colleagues recently followed 117 women in Rio de Janeiro with confirmed Zika infections during their pregnancies. All these women gave birth to live babies. Four percent of the babies had microcephaly. But nearly 38 percent of them had problems other than microcephaly, either at birth or three months later.  

"We had babies that had abnormal MRI exams of their brains, babies with eye abnormalities, babies who failed hearing tests and appeared to have significant hearing loss," Nielsen says. "And we had babies with fetal growth restriction" — a condition in which the fetus doesn't grow as it should in the uterus. In some cases, the mom was infected late in pregnancy, during the third trimester, and her baby still had problems. In contrast, with microcephaly, there appears to be little risk when the Zika infection occurs late in pregnancy.  

When Nielsen and her team saw how many babies had problems — more than 40 percent — they didn't believe the data at first. "We said, 'Wow that's really high. That's absurd,' " she says. "But then we looked at the data over and over again and we said, 'No it's correct.' " 

The study, published in The New England Journal of Medicine, has a major limitation: The control group had a very high rate of problems in their newborns as well. "Our control group was not entirely a control group," Nielsen says.

US: New York City has five babies born with Zika-related brain issue

Via The New York Times: New York City Has 5 Babies Born With Zika-Related Brain Issue. Excerpt:

At least four babies have been born in New York City with Zika-related brain developmental symptoms since July, the city’s health department said on Wednesday, bringing the total number of such births to five. 

The numbers were announced in an alert the Department of Health and Mental Hygiene sent to doctors, urging them to remain vigilant and to continue to warn pregnant women and sexually active women of reproductive age not using a reliable form of birth control against traveling to places where the virus is spreading. 

It was a reminder that while the threat of the virus may have eased in many places around the world, it still poses a danger and its consequences are likely to be felt for some time.  

Zika is primarily transmitted by mosquitoes but can also be passed on through sex. In most cases, the virus causes only mild illness, but the danger to women pregnant or trying to become pregnant is much greater, because of the impact the disease can have on fetal development. A small percentage of women with the virus have given birth to infants with a abnormally small heads and stunted brain growth — a condition known as microcephaly. 

As of Friday, about 8,000 New Yorkers have been tested for Zika and 962 have tested positive, including 325 pregnant women, according to the health department. 

All the cases were associated with travel; six involved sexual transmission by a partner who had been to the areas hit hardest by the Zika epidemic. 

In addition to the five babies with brain developmental symptoms, eight other infants have tested positive for Zika virus in New York City but have not shown evidence of what is being called congenital Zika virus syndrome. Though much of the early focus of public health officials centered on children born with microcephaly, there is concern that the virus could cause a host of other developmental problems, including brain and eye abnormalities, shortened or hardened muscles and tendons, and neurological impairment.

Brazil: Microcephaly found in babies of Zika-infected mothers months after birth

Every new thing we learn about Zika only makes it nastier. Via The New York Times: Microcephaly Found in Babies of Zika-Infected Mothers Months After Birth. Excerpt and then a comment:

It is the news that doctors and families in the heart of Zika territory had feared: Some babies not born with the unusually small heads that are the most severe hallmark of brain damage as a result of the virus have developed the condition, called microcephaly, as they have grown older. 

The findings were reported in a study of 13 babies in Brazil that was published Tuesday in Morbidity and Mortality Weekly Report. At birth, none of the babies had heads small enough to receive a diagnosis of microcephaly, but months later, 11 of them did. 

For most of those babies, brain scans soon after birth showed significant abnormalities, and researchers found that as the babies aged, their brains did not grow or develop enough for their age and body size. The new study echoes another published this fall, in which three babies were found to have microcephaly later in their first year. 

As they closed in on their first birthdays, many of the babies also had some of the other developmental and medical problems caused by Zika infection, a range of disabilities now being called congenital Zika syndrome. The impairments resemble characteristics of cerebral palsy and include epileptic seizures, muscle and joint problems and difficulties swallowing food. 

“There are some areas of great deficiency in the babies,” said Dr. Cynthia Moore, the director of the division of congenital and developmental disorders for the Centers for Disease Control and Prevention and an author of the new study. “They certainly are going to have a lot of impairment.”  

Dr. Deborah Levine, a professor of radiology at Harvard Medical School who has studied Zika but was not involved in either study, said there would most likely be other waves of children whose brains were affected by the Zika infection, but not severely enough to be noticed in their first year. 

 “A lot of the developmental abnormalities we’re not going to see until later,” she said. “There’s going to be another group seen later in childhood, I’m afraid, and another group probably when they reach school age.”

Mike Coston at Avian Flu Diary picked up the MMWR report. The repercussions are going to be major. Colombia, for example, has a minuscule number of Zika-related microcephaly cases, compared to Brazil. But are the Colombians now going to find themselves dealing with delayed congenital Zika syndrome?

For that matter, what about the children in the South Pacific born before Zika had reached Brazil? Has anyone followed up on them? Or on the Caribbean islands, Central America, and Mexico?

Brazil’s Zika crisis marks anniversary with more questions than answers

Via The Globe and Mail, Stephanie Nolen writes a superb overview: Brazil’s Zika crisis marks anniversary with more questions than answers. Excerpt from a must-read:

Quietly, gently, brutally, Vanessa van der Linden extinguishes hope. 

A year ago, Dr. van der Linden, a pediatric neurologist in the northeastern Brazilian city of Recife, found her clinic waiting room full of anxious parents holding babies with abnormally small heads. When she examined the babies’ brain scans, she saw crusts of calcium, or pockets of fluid, or blank spots where whole pieces of the brain were missing.  

It was Dr. van der Linden, plus her mother and brother, also pediatric neurologists, and a handful of colleagues, who began to trade stories and WhatsApp messages and then to raise an alarm – leading the Brazilian government to start an investigation into the strange new birth defects affecting babies in their area. Weeks later, her family and colleagues would tie the microcephalic babies to the Zika virus, a mosquito-born fever that was previously believed to cause only a mild fever and rash. 

A year ago, Dr. van der Linden did not know what to tell parents: no one had seen brain damage like this, caused by this virus, and it was impossible to give a solid prognosis. “We can’t take away the hope in the beginning.”  

But these days, she knows, and it is time that parents begin to accept the reality of what life will be like for their babies.  

“It’s difficult to talk to parents about a baby so small – but now, with one year, we can make a prognosis. They ask me, ‘Will my baby walk?’ And I always say to them, ‘it’s impossible to walk without head control or first sitting up, or interaction. A baby needs first to interact,’” she said, her voice steeled against the sadness of the last year.  

She has about 100 patients now, with confirmed Congenital Zika Syndrome, born at the crest of the epidemic last year. Of them, most are severely affected, she said; only 25 can interact at all. Most don’t make eye contact, can’t sit, have epilepsy, struggle to eat and to grow. 

“With time and with the life of their baby, the parents are coming to understand,” Dr. van der Linden said.