Category Archives: South America

El Niño and Possibly New World Primates Contributed to Zika Explosion

by Michelle Ziegler

The explosion of Zika-related birth defects this past year came out of the blue. Zika has been known since the 1940s but was seen as a mild dengue-like illness (Fauci & Morens, 2016). Leaving aside how and why microcephaly has appeared so dramatically, it is undeniable that Zika’s emergence and transmission in the Americas have been unusually rapid and extensive.

800px-Aedes_aegypti
Aedes aegypti from Tanzania (Source: Muhammad Mahdi Karim, 2009, GNU Free Documentation License)

Two papers published in December focusing on the Aedes mosquito vectors begin to shed light on how Zika was able to be established so quickly and pervasively. Zika utilizes the same tropical mosquito Aedes aegypti as dengue; it was once known as the yellow fever mosquito. It is also the vector of the chikungunya virus.

As first observed in West Africa many years ago, Zika epidemics followed a chikungunya epidemic by a couple years. Chikungunya was the emerging infectious disease of 2013, the year that Zika is believed to have arrived in South America (Fauci & Morens, 2016). Unrecognized by public health workers at the time, a Chikungunya epidemic was simultaneously chugging along under the radar in at least Salvador, the capital of the Bahai state of Brazil, during the peak of Zika epidemic of 2015 (Cardoso et al, 2017).

El Niño 2015-2016

In the first study by Cyril Caminade and colleagues at the University of Liverpool modeled Zika transmission in the two critical vector species in the Americas, the tropical Aedes aegypti found primarily in South America and the temperate Aedes albopictus found in the southern United States. It is thought that Zika transmits better from A. aegytpi but more research is needed to fully understand the differences. They developed a two vector, one host model where the climate is a variable to compare the effect of climate patterns on Zika transmission. They ran these simulations for each vector individually and together against historic climate data sets.

When they compared the worldwide distribution of the vectors and climate, they were able to show that all of the countries where Zika has been reported were predicted in their model. Ominously, South America was the most friendly region in the world for Zika (Caminade et al, 2016). The model for Zika produced a map that correlates extremely well with the global distribution of dengue. Due to the overlap of A. aegypti and A. albopictus territory, they found a high probability that Zika would transmit well in most of the southern United States.

f3-medium
Risk of Zika transmission based on their models A. winter of 2015-2016 B. Risk over the last 50 years. (Caminade et al, 2016)

The global climate anomaly known as El Niño is known to impact mosquito-transmitted diseases, so they had a particular interest in comparing the 2015-2016 El Niño to historic data sets. The map shows the predicted Ro (reproduction number) for Zika around the world in 2015-2016  and in the bar graph compared to the last 50 years. The conditions for Zika were the best for the last 50 years. Other hot spots that did not experience a Zika epidemic, like India, did have a record year for dengue. They also note that the African hot spot for ideal transmission conditions corresponds and to Angola where there was a Yellow Fever outbreak. In short, it was a very good year for Andes aegypti! And now, as of January 2017, Yellow Fever had added to their misery in a Brazil.

A Sylvatic Reservoir? 

Understanding if Zika will establish a sylvatic reservoir in South America is of vital importance for projections and mitigation of future Zika epidemics in Brazil and elsewhere in South America. Zika was initially detected in a sentinel monkey in Uganda and has since been detected in a wide variety of smaller primates in Africa and Asia. Using a model originally proposed for dengue they were able to show that primates with rapid birth rates and short lifespans are ideal for establishing sylvatic Zika. In primates with short life span, five years or less, and rapid birth rates, the establishment of a sylvatic reservoir is “nearly assured” (Althouse et al, 2016). They predict that a primate population as small as 6,000 members with 10,000 mosquitoes could support a sylvatic reservoir (Althouse et al, 2016). Ironically, since infection rate is dependent upon bites per primate, a small primate population with a large mosquito population is better at maintaining the reservoir than a large primate population. Old World monkeys like the African Green Monkey, a known African host of Zika, are already established in free-living troops in South American forests.  While A. aegypti favors human environments, A. albopictus prefers forested environments and has been spreading in Brazil.  It could be a prime candidate for a bridging vector between a sylvatic and domestic Zika cycle. Studies on Zika vulnerability and incidence in all South American primates has to be a priority. Our ability to manage Zika in the future depends on it.


References

Caminade, C., Turner, J., Metelmann, S., Hesson, J. C., Blagrove, M. S. C., Solomon, T., et al. (2016). Global risk model for vector-borne transmission of Zika virus reveals the role of El Niño 2015. Proceedings of the National Academy of Sciences of the United States of America, 201614303–28. http://doi.org/10.1073/pnas.1614303114

Cardoso, C. W., Kikuti, M., Prates, A. P. P. B., Paploski, I. A. D., Tauro, L. B., Silva, M. M. O., et al. (2017). Unrecognized Emergence of Chikungunya Virus during a Zika Virus Outbreak in Salvador, Brazil. PLoS Neglected Tropical Diseases, 11(1), e0005334–8. http://doi.org/10.1371/journal.pntd.0005334

Althouse, B. M., Vasilakis, N., Sall, A. A., Diallo, M., Weaver, S. C., & Hanley, K. A. (2016). Potential for Zika Virus to Establish a Sylvatic Transmission Cycle in the Americas. PLoS Neglected Tropical Diseases, 10(12), e0005055–11. http://doi.org/10.1371/journal.pntd.0005055

Fauci, A. S., & Morens, D. M. (2016). Zika virus in the Americas—yet another arbovirus threat. New England Journal of Medicine, 374(7), 601–604. http://doi.org/10.1056/nejmp1600297

The Super-spreading Landscape of Urban Dengue Fever

Dengue Fever is one of the most concerning emerging infectious diseases of the early 21st century. The virus has been spreading with its ever-expanding host, the mosquito Aedes aegypti.  For the last several years there have been naturally acquired cases of dengue fever in the United States and Europe, that are not connected to travel.

Aedes aegypti from Tanzania (Source: Muhammad Mahdi Karim, 2009)

Aedes aegypti‘s preference for the urban environment distinguishes it from most mosquitoes. It prefers to lay it eggs in small urban pools of water – flower pots, old tires, car ruts, buckets – rather than natural forest pools. As day-light feeders, bed netting would not be useful against A. aegpyti.  It has been known for some time that A. aegypti populations are driven by super-producing sites, pools of water that produce the majority of mosquitoes vs. pools that only produce a very few pupae.

It is known that dengue fever is transmitted by super-spreading events but it is unclear how this is tied to A. aegytpi super-production sites and other factors in the environment. To study this phenomena a group of researchers from Yale School of Public Health and the Institiuto National de Salud in Bogota, Columbia chose a dengue fever endemic neighborhood to study the major parameters in transmission. They identified three primary parameters to monitor.

  1. Distribution of super-producing A. aegypti sites across urban plots with similar characteristics. (Mosquitoes generally remain very close to where they hatch and are believed to be exposed to the virus and transmit it within the plot they hatched, or at most a neighboring plot.)
  2. Density of humans domiciled in the plots who can be infected.
  3. Human to mosquito transmission of the Dengue Fever virus. (Humans are the primary reservoir.)

Padmanabha et al devised a new index they call the epidemic potential, secondary infection rate (Ro) per capita.   They hypothesize that human density alters the epidemic potential by altering the dengue viral introduction rate and the secondary infection rate.  Padmanabha et al. note that viral transfer from human to mosquito depends on the number of mosquito bites per person, while viral transmission to humans from mosquitoes depends on the number of different people an infected mosquito bites.

They selected 16 similar urban plots in an endemic neighborhood in Columbia with a range of 41 to 142 homes (1-3 city blocks) with a human density of 3.2 to 4.5 residents per house. They surveyed A. aegypti pupae in water containers to estimate mosquito production and trapped mosquitoes to look for infected adults. Humans immune response to dengue virus was also surveyed over the season. The mosquito surveys were conducted seven times and human immune surveys three times over the season.  They excluded schools, churches and other civil locations were the community gathers from the plots.

Mosquito density results demonstrated super-production sites in each of the seven surveys within each patch. Only 5% of the house surveys accounted for 92% of the total mosquito pupae found. Pupal abundance accounted for nearly 80% of the variation in vector production.  Their model predicted an Ro of 0.88 to 3.87 and correlated with the number of infected humans introductions that produced 20 or more secondary infections; this is only 10% of model repetitions. In most cases introduced viruses to the patch  did not produce secondary infections. Analysis of human-to-mosquito transmission (viral introduction to the patch) and mosquito-to-human transmissions (secondary infections) suggest that both human density and vector abundance alter the dengue Ro and epidemic potential. Models using data generated by this study showed that the intersection of human density and vectors per household produced the best estimates of epidemic potential (Ro per capita). Padmandabha et al noted that “when viral introduction is accounted for, human density amplified the effect of A. aegypti super-production on dengue risk”.  As they monitored the community over the summer with seven surveys they were able to see the decline in super-production decrease the epidemic potential in areas of highest human density.

These super-productive habitats (at the level of individual homes) are seen here to be critical in producing super spreading events of dengue fever. All of the parameters for what makes a super productive habitat including human behavior have not yet been fully explored. This study looked at residential areas with the same socio-economic status. This team is planning further studies that look at a range of socio-economic communities and incorporate community centers like schools and markets.  Studies like this one will be useful for designing strategies to target insecticide programs and other efforts to reduce mosquito abundance and dengue risk.

References
Padmanabha H, Durham D, Correa F, Diuk-Wasser M, & Galvani A (2012). The Interactive Roles of Aedes aegypti Super-Production and Human Density in Dengue Transmission. PLoS neglected tropical diseases, 6 (8) PMID: 22953017

When Yellow Fever Came to the Americas

“Yellow Jack”, Cornhill Mag., 1892

In the early Americas, nothing scared people more than when Yellow Jack came knocking at the door of their city. Yellow Jack, or as we know it better today Yellow Fever, has rightly been called the plague of the Americas.

It has long been assumed that yellow fever came to the Americas with its vector, Aedes aegypti, in the hold of slave ships. These ships would have been an irresistible feast to the mosquito. Yet, little was known about the origin, locations, and dates of transmission to South America. Juliet Bryant, Edwarld Holmes and Alan Barrett (2007) looked to DNA analysis of yellow fever virus (YFV) strains from 22 countries ( 14 African and 8 South American) to resolve and date the phylogentic tree for YFV. They analyzed 133 isolates from humans and animal hosts collected over a 75 year period.

Bryant, Holmes and Barrett (2007: e75) made four clear observations.

  1. The American strains represent a single clade (monophyletic).
  2. There are two distinct sub-clades in east and west South America respectively.
  3. The South American clade is most similar to the West African isolates.
  4. The East African clade is the most distinctive.

These observations support an east or central African origin for the Yellow Fever Virus dominated by enzootic transmission. Its development parallels the transmission of its vector Aedes aegypti.

The split between the east and west African clades has been calculated to an average distance of 723 years (roughly 1284 AD). The West African isolates are the most diverse in Senegal, suggesting this was an early focus for West African YSF. From West Africa Yellow Fever was transmitted to Brazil a calculated average of 470 years ago (roughly 1537 AD). Early Portuguese seamen frequented this part of Africa and Brazil was their largest colony, founded in 1500. This suggests that Yellow Fever was transmitted to Brazil virtually from the beginning of the Portuguese colony. It is possible that Yellow Fever was one of the imported diseases brought by the Portuguese that decimated native Brazilians before large-scale importation of Africa slaves. The South American clade split into eastern and western populations when it was transmitted to Peru a calculated average of 306 years ago (roughly 1700). There is no evidence of transmission back to Africa or other areas where Aedes aegypti have spread in Asia. Byrant, Holmes and Barrett (2007) argue that sylvatic transmission is the primary means of maintaining YSF in South America. They note that there hasn’t been an urban epidemic of YSF in South America since 1928, unlike the annual urban outbreaks in West Africa.

Auguste et al (2010) confirmed the overall structure of the YSF phylogenetic tree in the Americas, including its Brazilian origin in the Americas. Their analysis of strains collected over the last decade also confirm that Brazil is the reservoir and origin for most strains in the Americas today with the Peruvian strains remaining primarily localized in Peru and neighboring Bolivia. The analysis of Auguste et al (2010) also supports enzootic maintenance and local evolution in areas of spread from Brazil such as Trinidad and Columbia.

What I find most surprising about the YSF tree is its relative youth. This all suggests that Yellow Fever originated in the Middle Ages and probably did not circulate outside of local areas of central Africa until the late medieval period. We still have a lot of learn about the landscape epidemiology of yellow fever including possible vertical transmission among mosquitoes and the importance of difference primate species as reservoirs. Although we have had an effective vaccine for decades, yellow fever is still a very clear and present danger in both the Americas and Africa.

References:

J E Bryant, E C Holmes, & A D T Barrett (2007). Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas PLOS Pathogens, 3 (5) : doi:10.1371/journal.ppat.0030075

Auguste, A.J., Lemey, P., Pybus, O.G., Suchard, M.A., Salas, R.A., Adesiyun, A.A., Barrett, A.D., Tesh, R.B., Weaver, S.C. & Carrington, C.V.F. (2010). Yellow Fever Virus Maintenance in Trinidad and Its Dispersal throughout the Americas, Journal of Virology, 84 (19) 9977. DOI: 10.1128/JVI.00588-10