Monday, January 22, 2018

WHO: Yellow Fever Update & Risk Assessment - Brazil

Yellow Fever  In Brazil - Credit WHO


Last year's Yellow Fever epidemic in Brazil was the worst in years (see epi chart above), with the virus is turning up in urban areas that have not experienced outbreaks in decades (see Brazil: Yellow Fever Updates From The MOH, The CDC, and University of Wisconsin).  
While the outbreak peaked in January, it lingered on until the end of April, with only sporadic cases reported until last December.  Since then, we've seen a tripling of new human cases, along with reports of outbreaks in non-human primates.
Last week, the WHO announced that Vaccination Recommended For Visitors to São Paulo State. Complicating matters, there remains a serious shortage of the Yellow Fever Vaccine (see CDC Announcement: Yellow Fever Vaccine Access).

Today the WHO has released the following DON (Disease Outbreak News) report on the rise in Yellow Fever cases in Brazil.  I'll return with a postscript:

Yellow fever – Brazil

Disease outbreak news
22 January 2018

From 1 July 2017 through 14 January 2018, 35 confirmed human cases of yellow fever were reported in Brazil (Figure 1), including 20 deaths and 145 suspected cases who are under investigation. In recent weeks, the number of confirmed human cases of yellow fever has tripled in Brazil, mainly in the states of São Paulo and Minas Gerais. Confirmed cases were notified in the states of São Paulo (20 cases, including 11 deaths), Rio de Janeiro (three cases, including one death), and Minas Gerais (11 cases, including seven deaths), and in the Federal District (one fatal case).

All confirmed cases are likely to have acquired their infections in geographic locations where there are documented epizootics in non-human primates. In Minas Gerais cases are reported in municipalities where no human cases were detected during the outbreak in 2016/2017. In São Paulo, the highest proportion of cases is reported in Maripora, an area located 15 kilometers from the northern area of the municipality of São Paulo. The new cases in Rio de Janeiro are reported in the municipalities of Valença and Teresópolis; the latter is located 96 kilometers from the city of Rio de Janeiro.

On 11 January 2018, a case of yellow fever was confirmed in The Netherlands (PCR positive) in a returning traveller with history of stay in the municipality of Mairipora and Atibaia, state of Sao Paulo, Brazil, from 19 December 2017 through 8 January 2018, an area where the circulation of yellow fever virus is currently occurring. The case has no history of yellow fever vaccination. The onset of illness was 7 January 2018, when the patient reported symptoms of high fever, headache, myalgia, nausea, vomiting and diarrhoea.

Although epizootics have been reported throughout 2017, there was a significant increase from September 2017. The high number of epizootics and animals concerned indicates a high level of circulation of the virus in ecosystems favorable for transmission. From 1 July 2017 through 14 January 2018, there were 2442 epizootics in non-human primates reported in 21 federal entities, including areas that were previously not considered to be at risk for yellow fever. Of these, 411 were laboratory-confirmed, 747 are under investigation, 817 were classified as indeterminate and 467 were ruled-out. The confirmed epizootics for yellow fever were reported by four states (Mato Grosso, Minas Gerais, Rio de Janeiro, and São Paulo); however, the majority (88%) of the confirmed epizootics were registered in the state of São Paulo.

Public health response

Since September 2017, when yellow fever was confirmed in human cases and epizootics in São Paulo, national authorities have been intensifying vaccination activities through routine and preemptive immunization campaigns. In addition, state and municipality health authorities have been strengthening healthcare services for management of cases and have been carrying out risk communication.

In early January 2018, to reduce the risk of a large yellow fever outbreak, the Brazilian Ministry of Health announced plans to conduct a mass yellow fever vaccination campaigns which will include both standard (0.5 mL) and fractional (0.1 mL) doses. The campaigns will take place in São Paulo and Rio de Janeiro, from 25 January through 17 February and in Bahia, from 19 February through 3 March. The aim is to vaccinate 21.8 million people (16.5 million with the fractionated dose and 5.3 million with the standard dose) who live in 77 municipalities in these three states.
WHO risk assessment

The number of epizootics reported since July 2017 continues to be a concern, especially near urban areas of large cities, such as São Paulo, and in municipalities that were previously not considered at risk for yellow fever.

While measures implemented by the Brazilian authorities during the 2016/2017 outbreak have contributed to the occurrence of a smaller number of cases when comparing the periods from 28 November 2016 through 15 January 2017 with 27 November 2017 through 14 January 2018. The large number of unvaccinated people who continue to live in areas with ecosystems favorable for transmission of the yellow fever virus represent a elevated risk for the change in the current transmission pattern.

It is expected that the decision of the Brazilian authorities to carry out a mass vaccination campaign against yellow fever, including standard (0.5 ml) and fractional (0.1 ml) doses, can effectively limit the transmission of yellow fever. It is important to note that, due to its scale and scope, this mass vaccination campaign will likely be characterized by significant logistical challenges.

The recent occurrence of a confirmed yellow fever case in an unvaccinated traveller reveals the need for States Parties to reinforce the dissemination of recommendations for international travellers.

The current WHO recommendations for international travellers going to Brazil were updated on 16 January 2018 and are available at the link below:
WHO recommendations for travellers, Brazil

Travellers returning with viraemia may pose a risk to the establishment of local yellow fever transmission cycles predominantly in areas where the vector is present.

To date, there has been no evidence of yellow fever transmission by Aedes aegypti. In entomological studies conducted during the 2016/2017 outbreak in some of the affected states, it was found that the isolated Haemagogus mosquitoes were positive for yellow fever.

WHO continues to monitor the epidemiological situation and review the risk assessment based on the latest available information.
         (Continue . . .)

While they don't mutate as quickly as influenza viruses, mosquito-borne viruses like Yellow Fever, Chikungunya, and Zika all evolve over time.

Until 2005, Chikungunya was a little known virus which was only found in East and Central Africa, and had never caused an urban epidemic. 
But after a new mutation emerged that allowed it to be carried by the Aedes Albopictus `Asian tiger’ mosquito (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential), the virus quickly cut a swath across the Indian ocean, into the Pacific, and eventually to Central and South America. 
Similarly, we've seen studies showing that A single mutation in the prM protein of Zika virus contributes to fetal microcephaly, and in Emerging Microbes & Infect: Growing Genetic Diversity Of Zika Viruses In Latin America, researchers found a high level of genetic diversity among Zika viruses sequenced from Brazil, with no clear sign of a dominant strain.
Not surprisingly, Yellow Fever has not been exempt from this evolutionary process.
Last May, in Fiocruz Institute: Sequencing Of Yellow Fever Virus Shows 8 Genetic Changes - Brazil, researchers sequenced the genome of two recent Yellow Fever viruses isolated from Howler Monkeys - and found a number of novel mutations (amino acid changes) that have never been seen in the Yellow Fever virus previously.

From the study, the authors wrote:
. . . .  we detected eight unique amino acid changes in the viral proteins, which are located in the structural capsid protein (1 change), and the components of viral replicase complex, the NS3 (2 changes) and NS5 (5 changes) proteins, suggesting a potential role in the capacity of viral infection to vertebrate and/or invertebrate hosts and spreading in the ongoing outbreak. 
Whether these specific changes are behind the sudden increase in Yellow Fever in Brazil remains to be determined, but scientists now have a plausible mechanism to investigate.

But beyond Yellow Fever, Zika, and Chikungunya this is a reminder than old scourges have a habit of reinventing themselves, and we can't necessarily assume they will always behave in the future the same way they have behaved in the past.

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