H5N1

Zika was soaring across Cuba. Few outside the country knew

Via The New York Times: Zika Was Soaring Across Cuba. Few Outside the Country Knew. Excerpt and then a comment:

A previously unknown outbreak of the Zika virus swept across Cuba in 2017, a year after the global health emergency was declared over, scientists reported on Thursday.  

Until now, the Pan American Health Organization had no record of any Zika infection in Cuba in 2017, much less an outbreak. Following inquiries by The New York Times about the new study, published in the journal Cell, officials acknowledged that they had failed to tally 1,384 cases reported by Cuban officials that year.

That figure is a sharp increase over the 187 cases confirmed in 2016 and is “in line with the estimates for 2017 from our own study,” said Kristian Andersen, an infectious disease researcher at Scripps Research Translational Institute in La Jolla, Calif., and a co-author of the new study. 

Because most cases of Zika go unconfirmed, Dr. Andersen added, the outbreak actually may have comprised tens of thousands of infections.

 Cuba saw record tourism in 2017, raising the possibility that many travelers were unknowingly exposed. Some 4.7 million foreign visitors arrived that year, an increase of 16 percent over 2016. More than one million were Canadians.  

“If we want to stay ahead of communicable diseases, we need to know where they are and how many cases are occurring,” said Jennifer Gardy of the Bill & Melinda Gates Foundation in Seattle. “For some diseases in some settings, this is pretty straightforward. For others, like Zika, it isn’t.” 

Officials at P.A.H.O., an arm of the World Health Organization, blamed the failure to publish timely data on the Cuba outbreak on a “technical glitch.” The information was held in a database, they said, but not visible on the website. By Thursday afternoon, the website had been updated.

"Technical glitch" indeed. I blogged about this outbreak last December, when the Cell study appeared on bioRxiv. It's a very quiet scandal, reminiscent of PAHO/WHO's refusal to identify the source of Haiti's disastrous cholera outbreak in 2010 and thereafter. (And the Cubans were also very quiet about the cholera imported from Haiti by their own returning healthcare workers.)

Preparing for emerging infections means expecting new syndemics

A letter in The Lancet: Preparing for emerging infections means expecting new syndemics.

When several sources of morbidity come together to produce interlinked and worse health outcomes, they are sometimes called a syndemic. Research on syndemics explores how two or more diseases cluster together; how social, political, economic, and ecological factors drive those clusters; and how clustered conditions interact via biological, psychological, or social pathways. Syndemic interventions target underlying patterns of multidirectional causality to achieve better overall health in susceptible and often dispossessed populations. 

So far, syndemic theory has found limited traction in fields such as ecoepidemiology that dominate emerging infectious disease research, despite a natural fit for three major challenges: proliferation of closely-related emerging viruses; co-occurence with endemic infections; and broader interactions with other aspects of health, including non-communicable diseases, mental health, and stigma. We show the relevance of syndemics for ecoepidemiology by showing how each of these complicates our understanding of the Zika virus epidemic in Latin America and the Caribbean. 

First, the idea of a syndemic formalises existing knowledge about co-occurrence of Aedes mosquito-borne viruses. Dengue and chikungunya viruses have had substantial comorbidity and co-infection with the Zika virus, including at least one case of triple coinfection. Many studies implicitly examine the three viruses as syndemic but do not refer to this linkage using the term. All three viruses are linked through Aedes mosquitoes to urbanisation, driving a broad spatial correlation between poverty, chikungunya, and Zika congenital syndrome (ZCS) in Brazil. Thinking syndemically could lead to mosquito control and public health education that targets several Aedes-borne viruses at once. 

Second, syndemic thinking has the potential to broaden conversations about co-occurring morbidities without adding confusion about causality. After scientific consensus resolved that ZCS was responsible for Brazil's microcephaly epidemic, conversations about other possible drivers were mostly sidelined. However, Brazil is a global hotspot of congenital toxoplasmosis, and microcephaly cases attributable to toxoplasmosis were observed during the Zika virus outbreak. 

Zika, toxoplasmosis, and microcephaly could create a syndemic, even without links between toxoplasmosis and the 2015–16 ZCS epidemic; poverty and environmental degradation connect them, as could fear and stigma. Syndromic surveillance for emerging pathogens like Zika the virus might be weakened by syndemic clustering between endemic and emerging infections of similar pathology or etiology, especially in poor and undersurveilled populations. 

Third, sexual transmission of the virus and fetal effects of ZCS introduced two new topics—safe sex and abortion access—that had never before been extensively discussed in an arboviral outbreak. Already, work focused on the syndemic of Zika virus, HIV, and unintended pregnancy, has identified marital and cultural risk factors that can help target interventions such as condom use and social policy, emphasising the promise of syndemic thinking, and the need for social scientists' involvement in outbreak prevention and management. 

The long-term effects of Zika virus might also be syndemic, as surviving babies become adults with a range of disabilities and sequelae. Although virologists work tirelessly to understand ZCS, this basic medical research remains disconnected from broader anthropological inquiries about the ongoing social effects of Zika. Bridging this gap is imperative to understand and improve quality of life in affected communities. 

The Zika virus outbreak in Latin America and the Caribbean will not be the last major outbreak; several new outbreaks have been reported across India. Other diseases will also raise complicated issues regarding safe sex or access to safe and legal abortions, and virologists have begun to anticipate sexual transmission and teratogenic effects of other emerging viruses. Increased knowledge of these select pathogens can help emerging disease researchers plan for syndemics of the future.

Impact of age-specific immunity on the timing and burden of the next Zika virus outbreak

Via bioRxiv: Impact of age-specific immunity on the timing and burden of the next Zika virus outbreak. The abstract:

The 2015-2017 epidemics of Zika virus (ZIKV) in the Americas caused widespread protective immunity. The timing and burden of the next Zika virus outbreak remains unclear. 

We used an agent-based model to simulate the dynamics of age-specific immunity to ZIKV, and predict the future age-specific risk using data from Managua, Nicaragua. We also investigated the potential impact of a ZIKV vaccine. Assuming lifelong immunity, the risk of a ZIKV outbreak will remain low until 2035 and rise above 50% in 2047. 

The imbalance in age-specific immunity implies that people in the 15-29 age range will be at highest risk of infection during the next ZIKV outbreak, increasing the expected number of congenital abnormalities. 

ZIKV vaccine development and licensure are urgent to attain the maximum benefit in reducing the population-level risk of infection and the risk of adverse congenital outcomes. This urgency increases if immunity is not lifelong.

The next Zika virus outbreak will affect young women of reproductive age disproportionately

Via bioRxiv: The next Zika virus outbreak will affect young women of reproductive age disproportionately: mathematical modeling study.

Zika virus (ZIKV) is a mosquito-borne flavivirus. In 2016, Managua, the capital city of Nicaragua experienced a Zika virus outbreak. Amongst confirmed cases, seropositivity increased with age and >50% of the adult population had ZIKV antibodies. 

The duration of immunity to ZIKV remains unclear. We used an agent-based model in a Bayesian framework to describe the dynamics of immunity to ZIKV, and predict the future age-specific risk of ZIKV infection in the population of Managua. We also investigated the potential impact of a ZIKV vaccine under different assumptions about the persistence of immunity. 

Assuming lifelong immunity, the risk of a ZIKV outbreak will remain low until 2035 and rise above 50% in 2047. Young women of reproductive age will be at highest risk of infection during the next ZIKV outbreak. 

ZIKV vaccine development and licensure are urgent, to attain the maximum benefit in reducing the population-level risk of infection and the risk of adverse congenital outcomes.

Venezuela: PAHO reports ten deaths and over 160 cases of diphtheria in 2019 alone

Via Efecto Cocuyo, a March 19 report: Diez muertes y más de 160 casos de difteria registra OPS en Venezuela solo en 2019. [PAHO reports ten deaths and over 160 cases of diphtheria in Venezuela in 2019 alone] Excerpt, with my translation, and then a comment:

La epidemia de difteria continúa activa. El brote que inició en el estado Bolívar a mediados de 2016 todavía persiste tres años después y sigue cobrando vidas. En su última actualización epidemiológica, con fecha de este lunes, 18 de marzo, la Organización Panamericana de la Salud (OPS) confirmó 10 muertes por esta enfermedad en Venezuela hasta la semana epidemiológica 8, es decir, hasta el 24 de febrero. 

The diphtheria epidemic continues active. The outbreak that began in Bolívar state in mid-2016 persists three years later and keeps taking lives. In its latest epidemiological bulletin, date Monday, March 18, the Pan American Health Organization (PAHO) confirmed ten deaths from this cause in Venezuela as of epidemiological week 8, February 24.

El organismo regional detalló que entre enero y febrero de este año se han contabilizado un total de 164 infecciones. Hasta la fecha, solo Venezuela y Haití han reportado casos de esta enfermedad.  

The regional agency noted that between January and February this year, 164 cases have been recorded. To date,only Venezuela and Haiti have reported cases of this disease.

Desde el inicio de la epidemia, la OPS señala en su reporte que Venezuela ha notificado más de 2.700 casos sospechosos, con 2018 como el año en el que se registró mayor número de contagios, un total de 1.198 casos.  

From the start of the epidemic, PAHO says in its report, Venezuela has reported over 2,700 suspected cases, with 2018 as the year with the largest number—a total of 1,198 cases.

Del total de notificaciones, 1.612 casos han sido confirmados hasta la fecha: 128 por análisis de laboratorio y 1.084 por criterio clínico o nexo epidemiológico.  

Of the reports, 1,612 have so far been confirmed: 128 by laboratory tests and 1,084 by clinical or epidemiological criteria.

De 2016 a 2019, la enfermedad ha cobrado la vida de 280 personas. El año pasado también fue el período en el que se registró mayor número de defunciones, con 150 muertes. Le siguieron 2017 (con 103) y 2016 (17).  

From 2016 to 2019, the disease has taken 280 lives. Last year was also the period in which most deaths were reported, 150. The year 2017 was second, with 103, and 2016 saw 17.

La OPS alerta que la tasa de letalidad de los casos confirmados aumentó, pasando de 20% en 2018 a 26% para este 2019.

PAHO warns that the case fatality rate of confirmed cases has risen, from 20% in 2018 to 26% in 2019.

Venezuela's health department stopped publishing regular bulletins sometime in 2016 or thereabouts. Since then, various professional groups have tried to estimate just how many Venezuelans have been falling ill with various diseases, of which diphtheria is only one. 

So I guess it's nice that the Maduro government is at least talking to PAHO. To the best of my knowledge, Venezuela never reported reliable numbers during the Zika outbreak, whether of Zika itself or Zika-related microcephaly and other neurological disorders. We will be a long time repairing the grievous lapses in South American public health caused by purely political decisions in Caracas.

Emergence of the Zika virus Asian lineage in Angola

Via bioRxiv: Emergence of the Zika virus Asian lineage in Angola. The abstract:

Background: 

Zika virus (ZIKV) infections and suspected microcephaly cases have been recently reported in Angola, but no data are available on the origins, epidemiology, and diversity of the virus. 

Methods: 

Serum samples from 54 suspected ZIKV cases, 76 suspected microcephaly cases, and 24 mothers of infants with suspected microcephaly were received by the Angolan Ministry of Health. Computed tomographic brain imaging and serological assays (PRNT) were conducted on one microcephalic infant. All sera were tested for ZIKV by RT-qPCR. 349 samples from HIV+ patients and 336 samples from patients suspected of chikungunya virus or dengue virus infection were also tested. Portable sequencing was used to generate Angolan ZIKV genome sequences, including from a ZIKV+ neonate with microcephaly born in Portugal to an Angolan resident. Genetic and mobility data were analysed to investigate the date of introduction and geographic origin of ZIKV in Angola. 

Findings: 

Four autochthonous cases were ZIKV positive via RT-qPCR, with all positive samples collected between December 2016 and June 2017. Viral genomes were generated for two of these cases, and from the neonate with microcephaly identified in Portugal. Genetic analyses and other data indicate that ZIKV was introduced to Angola from Brazil between July 2015 and June 2016. This introduction likely initiated local ZIKV circulation in Angola that continued until June 2017. The scanned microcephaly case showed brain abnormalities consistent with congenital Zika syndrome and serological evidence for maternal ZIKV infection. 

Interpretation: 

Our analyses confirm the autochthonous transmission of the ZIKV Asian lineage in continental Africa. Conducting ZIKV surveillance throughout Africa is critical in the light of presented evidence for autochthonous ZIKV transmission in Angola, and associated microcephaly cases.

Branswell: Developmental delays persist as Brazil’s Zika babies grow up

Via STAT, Helen Branswell writes: Developmental delays persist as Brazil’s Zika babies grow up. Excerpt:

The Zika virus has faded from the world’s headlines. But the damage the strange mosquito-borne virus inflicted on some children whose mothers were infected during pregnancy very much remains.  

A new study, published Wednesday in the New England Journal of Medicine, reports that in a group of Zika babies from Brazil who are being followed to assess their progress, 14 percent had severe developmental problems.  

This was higher than previous studies have suggested, said Dr. Karin Nielsen-Saines, one of the authors. 

These children scored unusually low scores on testing of their cognition, motor, or language skills, or they had visual or hearing impairment.  

“It was either both things or one or the other,” explained Nielsen-Saines, a professor of pediatric infectious diseases at the David Geffen School of Medicine at the University of California, Los Angeles. 

Nielsen-Saines and her co-authors, a number of whom are from Brazil’s Oswaldo Cruz Foundation, wanted to chart what Zika would do over the long term to children born to mothers infected during pregnancy. So they followed a cohort of 182 children. 

Of those, 131 were brought in by their parents for follow-up testing that involved at least one of the following: brain imaging, eye examinations, hearing tests, and a standardized test used to assess the development of children in the first few years of life. The test is called the Bayley Scales of Infant and Toddler Development, or Bayley-III. 

The testing was done in the second year of life for these young children, between the ages of 12 to 18 months in most cases. Nielsen-Saines said the work is ongoing and the group is currently assessing later data from these children, who they plan to study until at least the age of 7. 

Of the total, 94 of the children underwent both imaging and the Bayley-III assessment; 63 percent of them had scores that were in the normal range for cognition, motor, and language skills. But 14 percent had severe neurodevelopmental delays.

Six of the children had microcephaly and were so profoundly impacted that in essence the Bayley test could not be conducted, Nielsen-Saines said. Another roughly 15 percent had moderate developmental delays, she said.

No Zika virus update in Nigeria since 2016

Via healthnews.africa: No Zika virus update in Nigeria since 2016. Excerpt:

Zika virus is back on the global radar. With confirmed cases in the most populated countries in the world, China and India, concerns raised over Nigeria’s Zika virus preparedness since the most recent update was issued 2 years ago. Furthermore, Zika virus disease is not on NCDC’s directory of diseases that affect Nigerians although it had previously affirmed that Nigeria is at risk of the Zika virus disease. 

In its ZIka virus risk assessment for Nigeria, the NCDC stated: “NCDC plans to initiate surveillance to understand and monitor the epidemiology of Zika virus in Nigeria for the appropriate interventions.” But there has not been any official publicly available publication on the disease since.   

Zika is back 

Late October 2018, Chinese Customs Authorities reported they had detected the first case of imported Zika virus in 2018 in a man who had recently traveled to the Maldives. The tourist showed symptoms including a fever and rash when arriving at Baiyun International Airport on Oct. 19 in Guangzhou, south China’s Guangdong Province, according to the General Administration of Customs (GAC). 

Alarmed customs staff arranged a medical examination and found him Zika-positive two days later, the GAC said in an online announcement without identifying the patient, who was later quarantined at a local hospital.  

In a similar way, few days ago, the Zika virus disease reemerged in India with over 20 cases confirmed already thus raising concerns about Nigeria’s preparedness to prevent and contain an outbreak. 

Zika is different  

The well documented Zika virus experience in Brazil and across Latin America can be seen as a good overview of a classical outbreak of Zika virus disease. 

Between 2014 and 2016, a virus spread quickly through the Brazil and other Latin American countries, called Zika virus. Since it usually has very mild, or no symptoms, it took about a year for Brazil to confirm the first case of the disease. By then the outbreak was already widespread.  

It was not labelled a public health emergency until February 2016 when microcephaly – which is when infants are born with small heads with permanent brain deficits- and other neurological sequelae were noted in babies born about that time. 

The factors associated with the rapid spread of Zika virus in Brazil such as a population that may be non-immune, a high population density, a conducive climate and inadequate control of Aedes mosquitoes could also describe why many African countries are Zika virus-prone zone today. Most of West Africa is at risk of Zika virus including Nigeria, Ghana and Guinea Bissau. 

An invisible epidemic 

In April – June 2016, just as the outbreak in Brazil was spreading, cases of Zika virus infection and microcephaly in infants were reported in Guinea Bissau.  

In a 2017 Lancet article on the extent of Zika virus in Africa, about 6 out of 100 blood samples tested from people with fever in Senegal and Nigeria tested positive for the Zika virus infection. Zika virus was called the ‘invisible epidemic’ in the Lancet article.

Congenital brain abnormalities during a Zika virus epidemic in Salvador, Brazil, April 2015 to July 2016

Via Eurosurveillance: Congenital brain abnormalities during a Zika virus epidemic in Salvador, Brazil, April 2015 to July 2016. Excerpt from the discussion section, with my bolding:

In this study, we described a high prevalence of confirmed CBAs in Salvador, as high as 2.2% of the live births in December 2015. The prevalence of image-confirmed CBA estimated for the study period adjusted for one year was 52 times higher than the estimated baseline prevalence of microcephaly in the north-east region (average of 5 cases per 100,000 live births per year, between 2000 and 2014). Unfortunately, we did not have information on serological or virological ZIKV testing, which would allow ascertaining the aetiology of such an outbreak. 

However, the peak of births of babies with microcephaly occurred 30–33 weeks after the peak of ZIKV epidemic in Salvador, and this is consistent with the growing body of evidence suggesting that the first trimester of pregnancy is the period when ZIKV infections pose the highest risk of adverse fetal outcome. Taken together, it is reasonable to assume that most of the imaging-confirmed cases in this study were due to congenital ZIKV infection. 

As we only considered cases with specific neuroimaging findings as confirmed cases, we certainly underestimated cases of congenital ZIKV infection. Several suspected cases had not been investigated by the time we analysed the data and the imaging modality most commonly used was prenatal or postnatal intracranial ultrasound, which is not an optimal modality to detect abnormalities of the corpus callosum and cerebral cortex. 

In addition, suspected microcephaly cases were reported based on birth head circumference, which could be well within normal limits in some cases of congenital ZIKV infection. Although reporting of spontaneous abortions, stillbirths and fetuses presenting alterations in the central nervous system was also encouraged, allowing us to confirm a few cases with normal or large head circumference at birth, we could not evaluate whether there was an increase in abortions and stillbirths in Salvador during the study period. 

On the other hand, some cases counted as confirmed could be due to other causes such as congenital cytomegalovirus infection or genetic disorders, but the number of these cases is expected to be small, considering the baseline rate of microcephaly before the epidemic. In addition, in north-east Brazil (a region in which Salvador was one of the epicenters for the ZIKV outbreak), only 1.3% of confirmed cases of infection-related microcephaly during the 2015–16 period had laboratory evidence of syphilis, toxoplasmosis, cytomegalovirus, or herpes simplex.  

A similar increase in microcephaly cases was reported in other locations where ZIKV epidemics have occurred, such as Colombia, where the prevalence of microcephaly also increased around 6 months after the peak of ZIKV transmission in July 2016. However, the microcephaly prevalence reported in Colombia peaked at 17.7 cases per 10,000 live births, much lower than observed in Salvador. Potential reasons for this difference may include, variable intensity levels of ZIKV transmission, differences in circulating ZIKV strains and different case definitions and surveillance criteria. Further, co-circulation of other arboviruses (dengue and chikungunya, for example), differences in mosquito control measures, and prior exposure to yellow fever vaccination could be contributing factors. 

Additionally, Brazil was the first country in the Americas to experience a large outbreak of ZIKV and to detect an increase in microcephaly cases, and this allowed other countries as Colombia to issue recommendations for delaying pregnancies, which might have resulted in decreased risk of congenital abnormalities associated with ZIKV infection during pregnancy.

Zika in Africa: Rare birth defect on the rise in Angola

Via Thomson Reuters: Zika in Africa: Rare birth defect on the rise in Angola. Excerpt:

Emiliano Cula starts to cry as his tiny fingers, curled into a tight fist, are stretched by a physical therapist to stimulate motor control.  

Born in a poor neighborhood of Angola's capital Luanda, the 10-month old boy has microcephaly, a birth defect marked by a small head and serious developmental problems. He still can't sit upright and has difficulty seeing and hearing. 

"They don't know what caused it," Cula's mother Marie Boa says, sheltering under a blue umbrella from the summer rains. "The doctor said it might have been caused by a mosquito, but I don't know if that's true." The 18-year-old does not know whether her first child will ever walk or talk. 

Cula is one of at least 72 babies born with microcephaly in Angola between February 2017 and May 2018, suspected victims of an emerging Zika outbreak. The cases have gone largely unreported, but an internal World Health Organization report reviewed by Reuters concluded in April that two cases of a potentially dangerous strain of Zika confirmed in early 2017, along with the microcephaly cases identified since then, provided "strong evidences" of a Zika-linked microcephaly cluster in Angola.

A lack of data and diagnostic testing along with a woefully inadequate Angolan health system has made tracking the outbreak difficult. But new findings from a research team in Portugal suggest it is the first on the African mainland involving the Asian strain of the disease. 

It was the Asian strain that caused at least 3,762 cases of Zika-related birth defects, including microcephaly, in Brazil since 2015, as well as serious outbreaks in other Latin American countries. Doctors and researchers now fear it could spread from Angola to other countries on the African continent. 

In an emailed response to questions, Angola's ministry of health said it had reports of 41 cases of Zika and 56 cases of microcephaly since January 2017, when it began gathering data. It was not immediately clear why the figures differed from the internal WHO report.  

A lack of testing capacity means many cases of microcephaly go undetected, the ministry added, noting also that microcephaly has many causes.  

"Probably not all the cases of microcephaly can be attributed to Zika," the ministry said, listing a series of other potential causes such as syphilis and rubella. 

The Angolan outbreak comes at a time when world attention has moved on from Zika, and most of the more than $1 billion in U.S. funding allocated to fight the disease has been spent.  

"We can't let our attention down on this," said Eve Lackritz, a physician who leads WHO's Zika task force. "We have to stay vigilant and have a sustained response."