Photo Jonathan Blair

Thursday, December 3, 2015

Zika virus: trying to make sense of what we have

A friend writes the following: "the public health info released by the Brazilian government on zika and microcephaly is actually pretty good. [Still t]here is a fundamental methodological problem with all of this… zika may not be the source of the issue. The rise in microcephaly is correlated with a spike in zika, but it may not be the factor causing the condition [or it may be a] catalyst of some underlying aetiology."

He is certainly right on the mechanism: nobody knows yet. Maybe something else is causing the surge in microcephalia cases, which is the only really big news here: from 147 to 1248, for Brazil, and from 12 to 646, for Pernambuco, as of November 28 and 30). [References here and here].

For the rest, what we have is less compelling: in an interview, the head of the Dengue and Arbovirus society spoke of experimental results showing Zika to damage the brain of mice, but I have not seen—and I have looked for it—the  research he was referring to. For its part, the government’s acknowledgement of a link is based on the presence of the Zica virus in the blood and tissue of a single new born baby who died in Ceará. The virus was also found in the amniotic liquid of pregnant women in Paraiba (Pernambuco's northern neighbour state).

The broader nervousness is based on a significant number of interviews of mothers of newborns with microcephalia, a large proportion of whom reported suffering from Zika-like symptoms (which could have been dengue) during the first months of pregnancy, and on a time correlation: the surge in mosquito infections, as proxied by diagnosed dengue cases, began 10 months ago and went on for 20 weeks (week 5 to 25 of 2015, see the graph below), which corresponds to the beginning of the surge in affected newborns’ beginning on week 40-41 (beginning of October) and quickly increasing after that, which is more or less what appears to be happening. Nobody knows precisely if, for how long, and where Zika had been transmitted to people by aedes aegypti, but if the hypothesis is right, the next 15 weeks will tell. Moreover, many of the zika cases identified over the last year may have been misdiagnosed as dengue. Carlos Brito, a member of the Health Ministry's Arbovirus technical committee considers for instance that "of the dengue cases identified in the State (of Pernambuco), 80% were, in fact, zika cases."

Now, 80% may look like a lot, so let's do the math. As of November 16, according to the Health Ministry, there had been 83,601 "probable cases of dengue" in Pernambuco.

Most of the cases of dengue being asymptomatic (in a proportion of between 1.8:1 13:1), this must be considered an absolute floor. But to play "safe," let's stay with the cases identified. Zika cases misdiagnosed as dengue would thus number around 67,000 for the state or about 0.8% of the its population.  Assuming that Pernambuco's share of birth is proportional to its share of Brazil's population (4%), it would have had about 120,000 births in 2014 (Brazil's total was about 3 million, or 1.5% of its population). Using this as a proxy for the number of pregnancies, and factoring the fact that the peak infection period is about four months-long, this would imply a floor of about 350 pregnant mothers infected by the Zika virus in Pernambuco over the course of 2015. As noted above, there are already more than 600 cases of microcephalia this year in the state…

In other words: if there is indeed a causal link between zika and microcephalia, the number of zika infections that should be used as a basis of impact assessment has to be much larger than even 80% of the suspected number of dengue cases. In addition, the calculations made above and leading to the projected 350 cases assumes that 100% of pregnant mothers transmit the virus, and that 100% of the foetuses are affected by it. Anything lower than that would massively increase the hypothetical number of infections.

Zika virus: the surreal epidemic that has Brazilian doctors tell women not to get pregnant

A little-known virus called Zika has led, on November 29, to the declaration of a state of emergency in Pernambuco, Brazil's fourth most populous state. An unusually large number of suspected cases of microcephalia  among newborns has been detected here over the last few months. The babies affected have an abnormally small cranium, a condition that is  often associated with intellectual and developmental disabilities. This week-end, Brazil's health ministry has formally established a link between the presence of the virus and that condition, which however may also have a variety of other causes, from syphillis to malnutrition. Still, the number of suspected cases of microcephalia identified up to now this year (more than 1,000 in the country as a whole as of November 30, and around 500 in Pernambuco alone) significantly exceed the normal incidence of cases in Brazil, which have ranged between 139 and 175 per year since 2010. In addition, a small number of infected people have died in recent days, including a few adults, though it is unclear if the virus itself was the cause of death, if it interacted with another disease, or if the person died of an unrelated condition.

The virus is transmitted by a mosquito, aedes aegypti which is also a vector for two increasingly common diseases in Brazil: Chikungunya and especially dengue fever, which has reached epidemic proportion in the country.

Symptoms of Zika are similar to those of dengue fever: high temperature, headaches, joint and muscular pains as well as spots on the skin. They disappear after a few days. A significant proportion of people infected by dengue fever, however, are asymptomatic, and the same could be true of Zika. Finally, many dengue fever diagnoses have been based on clinical assessments instead of blood tests and an unknown proportion of presumed dengue patients or asymptomatic dengue carrier may thus have been in fact infected by the Zika virus.

Specialists and government officials currently think that foetal infection leading to microcephaly occurs when mothers are inoculated with the viruses in the first three months of pregnancy, in a period crucial for the development of the foetal brain and before the placental barrier is fully formed.

The possibility that Zika is already widespread or that it could quickly expand to the whole country is based on the large number number of diagnosed cases of dengue, which increased between 2014 and 2015 from 555,000 to 1.5 million (as of November 16). Such a sharp increase clearly indicates that efforts to get rid of the mosquito are unsuccessful. The prospect that, by infecting pregnant women, aedes aegypti could now produce a large number of cases of microcephaly magnifies the severity of the health challenge that dengue and Chikungunya fevers already represents.

The state of emergency has been declared in Pernambuco, which enables the state government to draw from special federal funds may be extended to other states in the coming days. The federal government has set up an inter-ministerial working group to tackle the crisis and is mobilizing research capacities and seeking international support to better understand what remains an extremely poorly known virus (CDC and WHO missions will come to Brazil later this week to discuss the crisis). The effort at this point focuses on the elimination of the mosquito. In addition, the government encourages pregnant women to wear long sleeves and pants, to close windows and doors and to use insect repellent.

The spectre of large-scale microcephaly occurence is obviously the dominant preoccupation of the government and health specialists. This has led a specialist to make  a most extraordinary health recommendation: in an interview posted last week-end on the website of Veja, Brazil's most widely read weekly, Artur Timerman, a virologist and President of the Brazilian Society for Dengue and Arbovirus (mosquito-transmitted), recommended that Brazilian women postpone pregnancies until the risks involved are assessed, which may take months. When asked by the female interviewer what women who were already pregnant should do, he fell back to dress codes and insect repellent recommendations, though noting that the efficacy of the latter was limited.

The elephant in the room is the issue of abortion, which is illegal in Brazil except for cases of rape or danger to the life of the mother. The question is extremely delicate in a country that is much more conservative, especially on that issue, than its international image would suggest. Given that the surge in dengue fever typically takes place between the end of February and June (week 7-23 of each year), most foetuses affected this year would be due between December and the end of March. This would imply impossible, extremely late or very risky pregnancy interruptions for this cycle, but a significant incidence of microcephaly in coming months would precipitate a huge debate in 2016. The tenor of that debate would be unprecedented, and not just for Brazil.

As the world's governments are meeting in Paris to talk about climate change and what it could mean for the future, a very ugly side of that future may already be showing at the door. A situation is developing in the planet's fifth largest country that may force its society to consider "postponing" or interrupting pregnancies on a massive scale to avoid the birth of a possibly very large number of severely disabled newborns. The fact that the vector of that potential epidemic is an insect that has adapted perfectly to the messy and increasingly warm urban context in which much of the population of the world already lives, and the fact that this insect is already showing resistance to common insecticides just boggles the mind. With Aedes egypti already roaming a very broad strip of the world's surface, and with the Zika virus quickly spreading beyond Brazil, expect this little post not to be the last you read on this topic.

[A slightly different version of this post was first published on]

The cat is out of the bag in Brazil as the PT itself throws Dilma under the bus

It looks like it is the PT itself that has decided to dump Dilma Rousseff from the presidency.
The presidency had asked PT members on the Ethics Council of the Chamber of Deputies to support the Eduardo Cunha, the President of Chamber. The man is completely rotten and everybody knows it BUT he had the power to accept or refuse a formal request to launch the impeachment process. They voted against Cunha and, predictably, the latter immediately answered by launching the process.
More discussions and negotiations are in the works, but Rousseff's position is much weaker as a result.
What could explain the party's attitude? I see two things, that may overlap.
1) The country is going through a massive multidimensional crisis. The economic situation is dire (growth for 2015: -3%; inflation >10%; unemployment bordering 10%, double of last year); a national health emergency could soon develop around the Zika virus; and the Petrobras corruption scandal is reaching ever deeper into the political establishment. Except for the latter--which is getting ever closer to Lula himself--leaving someone else to deal with the mess would increase the chances of a victory in the 2018 presidential crisis, where Lula, if he is still standing, would have the best chance of winning among all possible PT candidates.
2) Many in the party's base--the so-called social movements--are up in arms against the current Finance Minister's austerity package, and deeply critical of Dilma Rousseff's giving cover to it.
The first is most likely, but don’t underestimate the second, as Lula could himself be thrown under the bus by his various close friends who are currently negotiating plea bargaining deals with federal prosecutors. If he falls, it will be civil war inside the party, and looking good right now may pay off. 
For the details (worth translating), see this Folha de São Paulo article and, for background and a very careful presentation of the next steps, this, from the Financial Times.