Sunday, July 10, 2011

Yellow Fever


This week on Infection Landscapes we will discuss yellow fever, one of the first diseases identified as being vectored by mosquitoes as well as one of the first recognized hemorrhagic fevers. This post will conclude the extended special series on arthropod-borne infections that began over six months ago.

The Pathogen. Yellow fever is caused by an enveloped, single-stranded RNA virus. It is a Flavivirus, in fact the original Flavivirus, in the Flaviviridae family, which also includes dengue virus, hepatitis C virus, West Nile virus, Japanese encephalitis virus, and the other encephalitide viruses. Here is a picture of the yellow fever virus from the Hardin Library at the University of Iowa:

Electron micrograph of yellow fever virions

Flaviruses take their name specifically from the yellow fever virus, which is derived from the Latin word for yellow, flavus. Yellow fever virus invades primarily the macrophages and dendritic cells. Here is a nice graphic that depicts common life cycle elements that are generic to Flaviviruses, including yellow fever virus:




The Vector and the Landscape: Aedes aegypti mosquitoes are the most important vectors for the human transmission of yellow fever, which, you will recall, was also the case for dengue fever. Several other Aedes and Haemagogus mosquito species are also relevant for the transmission of yellow fever, but Aedes aegypti is particularly important because of its adapted ecology to the human domestic environment. Even though they share a primary vector, the transmission of yellow fever is different from dengue fever in that there are three quite distinct cycles of disease transmission. Because several vector species engage these different cycles, yellow fever reflects different disease ecologies and thus a unique landscape epidemiology for each of the transmission pathways. Dengue fever remains (for the most part) bound to an urban transmission cycle, which narrows the ecology of transmission considerably.

Historically, A. aegypti became famous because of its transmission of yellow fever. The realization that A. aegypti was a major problem with respect to yellow fever came from Cuba. In fact, since yellow fever was the first infectious disease identified as being transmitted by way of mosquito, the mosquito hypothesis of disease transmission, and thus vector-borne disease transmission, was established through work done in Cuba. Often, Walter Reed is credited with the work in Cuba that established the vector relationship and led to the elimination of much of the yellow fever endemic there in the late 1800s. However, it was the Cuban doctor, Carlos Finlay, who identified and proposed the mosquito as the vector for yellow fever in 1881, and which Walter Reed was able to mobilize his significant United States military resources to test extensively. Walter Reed, nevertheless, did assign the credit for the discovery properly to Dr. Finlay. But Western history remembers it differently, probably because Western history was not written by the Cubans.

Carlos Finlay

So let's examine this mosquito vector more closely. Here is a map produced by the World Health Organization (WHO) showing the current global distribution of A. aegypti:

Red+BlueA. aegypti is present


And here is a close-up picture of this vector: 


Aedes aegypti


To begin, we must emphasize that this mosquito has a very particular preference for the water environment it selects for laying its eggsIt likes SMALL containers that collect rainwater. And the mechanics work as follows. This mosquito does not lay its eggs either in the water or on the surface of the water, as most other species do. Instead, A. aegypti lays its eggs above the water on the interior wall of the vessel containing the water so that when the water vessel is refilled, from the water line at which the mosquito laid its eggs to the lip of the vessel, the eggs will have enough time to complete their developmental cycle to adulthood before evaporation depletes the water source. A truly incredible evolutionary adaptation.


Here are the stages of the mosquito life cycle (picture by Hopp MJ and Foley J. Global-scale Relationships Between Climate and the Dengue Fever Vector Aedes Aegypti. Climate Change. 2001; 48: 441-463):



In this picture below taken by the Centers for Disease Control and Prevention (CDC), notice the ovipositioning that leaves a ring of eggs just above what was, at one point, the water line:



This mosquito is originally adapted to a forest habitat wherein it would seek out holes in trees that would regularly collect rainwater. Tree holes are much more ubiquitous than you might think in a forest (think woodpeckers), and so this was quite an effective niche for this mosquito. As humans encroached more and more on forest habitat establishing agriculture, and building increasingly dense communities and living conditions, A. aegypti readily adapted to the new circumstances. The mosquitoes found an abundance of new and highly effective small containers strewn in and around households that can easily collect, or are intended to store, water. The mass production of plastics has been a major factor in the proliferation of potential water containers. Today A. aegypti is just as much an urban mosquito as it is a forest mosquito and probably more so. As such, A. aegypti is now uniquely adapted to the human environment. Unlike other mosquito species, they will often live in the household with humans, and can complete their whole life cycle here. They also bite during the day, so they have unlimited access to humans for taking blood meals. And finally, this mosquito's preferred host, as you may have already guessed, is humans.Because this mosquito is so very effective at exploiting the human environment, it is also very effective at transmitting any viruses that it is capable of carrying and which are infective to humans. 
     
So, what of the landscape of yellow fever? The reality is that the ecology of yellow fever is more complex than that of the other virus transmitted by A. aegypti that we covered previously (i.e. dengue fever).

Yellow fever has, in fact, three distinct cycles of transmission. All are mosquito-borne, but the ecology and landscape epidemiology of each is unique. Importantly, humans, themselves, often serve as the bridges between these different transmission cycles.


The urban cycle is most clearly delineated by the human environment and, thus, primarily involves A. aegypti mosquitoes since these are some of the most anthropophilic mosquitoes known. Humans are the reservoir for this cycle, but since mosquitoes can transmit the virus transovarially they may also serve as a reservoir.


The sylvan cycle (i.e. jungle cycle) involves two genera of mosquitoes: Aedes and Haemagogus. These mosquitoes transmit the virus primarily to non-human primates, which serve as the reservoir. Other mammals may be infected in this cycle but are not likely to be important for the maintenance of the viral ecology. These two cycles, the urban and the sylvan, occur in both South America and Africa and so are relevant transmission cycles in both macro-regions. The sylvan cycle in Africa requires A. africanus to maintain the viral ecology. However, the sylvan cycle in South America is the only transmission cycle that does not involve aedine mosquitoes.

Haemagogus mosquitoes are the critical vectors in the South American sylvan cycle of yellow fever. They are distinctly tropical forest mosquitoes, typically living out their lives in the forest canopy. Having adapted to a somewhat narrower ecologic niche, these mosquitoes oviposition in tree holes, the crevices of tree bark, or within exposed bamboo stalks. The mosquitoes deposit their eggs directly on the surface where the eggs, similar to the aedine mosquitoes, will develop once they are immersed in water following the next rain. As mentioned above these mosquitoes transmit the virus primarily to non-human primates, especially those that occupy the canopy. Humans are at risk of infection in this transmission cycle when they come into contact with this forested habitat, particularly when that contact actually disrupts the habitat. This scenario arises with deforestation and the development of natural habitat for agricultural or resource extraction purposes. Transmission to humans via this cycle is typically limited to workers in industries that encounter this forested habitat, where sporadic cases, or occasionally, small-scale outbreaks are the norm.

Bridge between sylvan and urban transmission cycles in South American yellow fever

In the African sylvan cycle, the analogue to Haemagogus mosquitoes is Aedes africanus. This mosquito has a very similar ecology to the South American Haemagogus species. It lives in the forest canopy and takes blood meals primarily from non-human primates, which serve as the reservoir for the yellow fever virus. The ovipositioning of A. africanus also mimics that of the Haemagogus mosquitoes. Transmission to humans in the African sylvan cycle also affects workers involved in deforestation, but is not limited to this population. Unfortunately, conflict in certain regions of sub-Saharan Africa where sylvan yellow fever is endemic exposes refugees and displaced communities to this cycle, and has ultimately resulted in more severe outbreaks in this setting than has been experienced in South America.

The intermediate cycle (i.e. the savannah cycle, or the rural cycle) occurs only in Africa and involves several different species of Aedes mosquitoes in the transmission of the virus. As the name suggests, this cycle occurs in the landscape between the strictly forest, or sylvan, cycle and the strictly domestic, or urban, cycle. As such, the Aedes spp. involved typically obtain blood meals from both humans and monkeys. It is essentially an ecotonal cycle, wherein the geography of transmission is determined by landscapes of transition from one habitat to another.

Bridges between sylvan, intermediate, and urban transmission cycles in African yellow fever 


The graph below depicts the relevant mosquito vectors for the different transmission cycles occurring in Africa and South America (published in Annu Rev Entomol. 2007. 52:209-29


We can see from this presentation that the occurrence of yellow fever is not geographically uniform. Rather, it results from transmission processes that occur in response to distinct, yet sometimes overlapping, vector ecologies, which themselves are geographically demarcated by unique features of the landscape. The ways in which humans encounter and navigate such landscapes will often determine the nature of disease endemicity.

The Disease: As with many other arboviruses and/or hemorrhagic fevers, yellow fever manifests as a range of clinical disease rather than one distinct condition. In areas where the virus is endemic, some infections may be entirely asymptomatic; the opposite end of the spectrum constitutes a severe, life-threatening illness. Overall, however, the case-fatality is high: approximately 20% among populations where the disease is endemic, and possibly as high as 90% among persons from non-endemic areas (typically travelers). Under-reporting of subclinical or mild disease undoubtedly inflates these numbers somewhat, but it is, nevertheless, an extremely serious infection.


There are typically three distinct phases of the clinical presentation of yellow fever:






Phase 1 corresponds to the host's initial viremia and typically presents with nausea and vomiting, fever, headache, dizziness, and myalgia. Leukopenia may be identifiable at the beginning of the acute symptoms, while liver enzymes typically increase a few days later. The viral load will typically reach its maximum 2 to 3 days after the initial infection. Importantly, those cases that end in fatality will often have a higher and extended duration of viremia relative to non-fatal cases.


Phase 2 is known as the remission, which, as the name suggests, can be identified by a break in the fever and relief from the clinical symptoms. The remission can last up to 2 days, but is not a necessary part of the natural history of disease. Some persons do not experience any remission in their clinical course. On the other hand, some infected persons will recover entirely during this remission and are referred to as abortive infections. These persons also do not demonstrate the jaundice associated with the severe third phase, from which the disease and the virus derive their names.


Phase 3 is referred to as the intoxication phase, and is the period of greatest clinical severity. Approximately 15% of infected individuals enter the intoxication period, when more advanced liver dysfunction begins to manifest. Jaundice is typically present, along with the return of nausea, vomiting and fever. Due to the associated coagulopathy, bleeding diathesis is also common at this stage. Multiple organ failure is common, with kidney, heart and neurologic involvement, depending on the extent of liver damage. As mentioned above, the case-fatality is 20% among endemic populations.


Epidemiology Summary and Control: Roughly 200,000 cases of yellow fever occur each year, with about 30,000 associated deaths. Here is a map produced by the World Health Organization (WHO) showing those geographic areas at risk of yellow fever virus transmission and those areas with reported outbreaks:

Countries at risk of yellow fever and countries that have reported at least one outbreak of yellow fever, 1985-1999

The continent of Africa experiences 90% of these cases, with the rest occurring in South America and Panama. Dramatic epidemics involving up to 100,000 cases each have been documented in the tropical countries of Africa. Outbreaks have also been identified in the Americas, but these are much less common in the western hemisphere in modern times. Historically, however, large-scale epidemics were experienced throughout all of the Americas on a regular basis. Here are two more WHO maps showing where yellow fever has occurred during the last half of the twentieth century. Also shown are the lines demarcating current endemicity in Africa and the Americas:



There was a point in the history of yellow fever when great gains were achieved toward its control, at least in the western hemisphere. Following the recognition of A. aegypti in transmitting yellow fever, a massive campaign was undertaken to eliminate the mosquito from the surrounding tropical forests during the building of the Panama Canal, with modest effect. However, in 1947 the Pan-American Health Organization (PAHO) began a massive program to eliminate this mosquito from the whole of the Americas. And this time the campaign was extraordinarily successful. By 1972, A. aegypti had been eliminated from 73% of the habitat that it occupied prior to 1947,primarily without the use of insecticides. However, when it was discovered that a jungle cycle of yellow fever existed that could not be eliminated by the campaign, tragically the intensive program was abandoned. By the close of the twentieth century, A. aegypti had newly colonized more geographic area than it had prior to 1947, and occupied a much greater global distribution as well. This has important implications not only for yellow fever, but also for dengue fever. This map published by Emerging Infectious Diseases tells the story best:

Shaded areas indicate presence of A. aegypti

And here again is the map demonstrating the current global distribution of this mosquito:

Red+BlueA. aegypti is present

The PAHO program was so effective in eliminating A. aegypti because it utilized a campaign to eliminate all open water containers in and around the household in every community.While this was an extremely labor intensive public health intervention, it was simple to employ and it only needed to target places of human habitation. However, the identification of a jungle cycle that could still make yellow fever viable resulted in the abandonment of the intensive campaign, and, thus, the resurgence of A. aegypti followed. Because of massive and effective yellow fever vaccination campaigns in the Americas, the consequences of this resurgence in the western hemisphere are far more relevant to the emergence of epidemic dengue fever than they are for epidemics of yellow fever.  

The large disparity in yellow fever incidence and mortality that currently exists between Africa and the Americas is largely due to the massive vaccinations campaigns that have been undertaken in many countries in South America, which have thus eliminated the urban cycle of disease in the western hemisphere. In many endemic African countries the same resources have not been available to mobilize widespread vaccination. This lack of vaccination, coupled with the added intermediate transmission cycle, have been important contributors to the much higher disease burden we see in Africa today.

This concludes the extended series on arthropod-borne infections. The series was by no means exhaustive and I will, of course, return to these and new arthropod-borne infections in future on an individual basis. Nevertheless, I think this series has served as a good general survey of many of the important arthropod-borne infections.

Next time at Infection Landscapes I will cover measles. Stay tuned. 

33 comments:

  1. The discovery of yellow fever being transmitted by mosquitos must have been a ground breaking discovery in public health. What tests did Walter Reed and others conduct to fing this mode of transmission?

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  2. Since the Aedes Egypti is a common vector for both Yellow Fever and Dengue, it is possible for the mosquito to be co-infected with both pathogens at the same time ? And is there any potential for exchange of genetic material between the two species ?

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    1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749261/

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  3. Two different areas of questions emerged for me as I read this:
    1. Have there been any studies delineating the precise correlation between woodpeckers and the jungle version of yellow fever or are woodpeckers just an urban jungle thing?
    2. Does the vaccine protect against all 3 types of yellow fever? I ask because you mention the American success with the vaccine, is the vaccine not successful in Africa or just not as heavily implemented?

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    1. I'll try to correctly answer your two questions, Deanna.
      1. I think the mentioning of woodpeckers is too draw attention to ways in which habitats conducive to Aedes Aegypti mosquito reproduction. That is, woodpeckers create hollows in trees than can collect and empty rainwater. So, this is more of a tool these mosquitoes use to maintain its sylvan cycle. It is important for laying eggs.
      2. I think the vaccine used in both regions is the same and would be just as effective in both regions, if the same resources and reach surrounding the Americas' effort were scaled to that of the African region. Reaching various peoples throughout different socioeconomic levels and geographic landscapes would take a great deal of money, labor, and time. And, these efforts have not been committed to Africa; thus, the disparity in yellow fever persists.

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  4. Deanna,
    It seems that the vaccine protects against all three cycles of yellow fever. Human habitation and geography play an important role in the intervention process. The PAHO program and more intense vaccination campaigns in the Americas appear to account for the large disparity seen between Africa and the Americas.

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  5. Jamal,
    I read that Walter Reed and his team engaged human experimentation to test the 'Mosquito Hypothesis'. Various subjects (including team members) were directly inoculated using infected mosquitoes. Based on the rates of infection and several fatalities, it was established that mosquitoes were the vector.

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    1. Inoculating subjects with infected mosquitoes was certainly very unethical if it is true that this is how Walter Reed established the "Mosquito Hypothesis." It is indeed unfortunate that lives had to be lost to prove this theory. If this allegation is true then the good doctor would have violated the phrase "first do no harm" even if some of the subjects were willing volunteers.

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    2. I agree that Walter Weed’s using healthy human to carry out experiment was unethical, however the courage of the volunteers is tremendous as the mystery of yellow fever was solved and thousand of lives has been saved. I feel volunteers for the experiments represented a broad range of interests for participation such as self-interest. This is true even today, as inducements for the participation in clinical trials ( such as Cancer research) include monetary payments, free check-ups, or receiving a potentially life-saving drug.

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  6. Thanks for the illuminating post. As far as interventional attempts go, PAHO seems pretty good, although difficult. As its been recently shown that Ivermectin prevents a aegypti from breeding and that treatment of a village with ivermectin reduces prevalence of malaria, do you think that this would be an effective treatment for yellow fever as well?

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  7. Studies suggest that ivermectin has harmful effects on the nervous, reproductive and digestive systems of the aedes aegypti mosquitoe. Although some have proposed that ivermectin be used for malaria prevention, there are no studies that support that ivermectin is useful for prevention of yellow fever, other than suggestive harmful effects to the organ systems above.

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  8. One effective approach in yellow fever prevention has been to kill the developing larva using both larva-eating fish and chemical larvicides. One recommended larvicide is Pyriproxyfen since it is effective in small doses and safe for humans.

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  9. The information, you have provided here is very useful, both for professionals and public. I normally tell my patients to read your articles about Infectious diseases. I have also used some of your images on our website. www.travelcliniccoventry.co.uk
    Please let me know, if you have any objection. I have put link to your website, from the page, where I used your images.
    Thanks for your hard work, to create a healthy planet.

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  10. Dr. Singh,
    Thank you very much for your interest. I am very happy for you to share this information and to use it in whatever way you can to communicate and teach others about these infections. I have no objection at all, and, in fact, I am only too pleased that this material can be of service to you.
    All the best to you,
    Michael

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  11. Claire,

    I found an interesting abstract that discusses two subspecies of Ae. aegypti, Ae. aegypti formosus (Aaf) and Ae. aegypti aegypti (Aaa)

    From the abstract: "Northwestern Aaa collections have a high disseminated infection rate (DIR) while southeast Aaf collections have a low DIR associated with a midgut escape barrier for DENV2".

    Other wise I couldn't find anything else about the mosquito being co-infected with both pathogens. Maybe some of the different distributions and characteristics of the diseases prevents co-infection.

    Here’s the link to the paper if your interested: http://www.labome.org/grant/r01/ai/yellow/feverdengue/yellow-fever-dengue-virus-competence-in-aedes-aegypt-aegypti-formosus-in-senegal-7696878.html

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  12. Thanks Michael. God bless you and all the best.
    www.drsingh.org.uk

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  13. One of the most interesting points of this topic, I believe, is the campaign made to eliminate yellow fever mosquitoes from South America. The fact that the efforts of the PAHO were simply abandoned seems a little off to me. It seems more reasonable that, after the discovery of the jungle cycle yellow fever, the PAHO would have made stronger attempts to eradicate the disease rather than abandoning it. Were there any alternative attempts to eradicating these types of yellow fever in South America?

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  14. finding that a mosqitoes transmit the yellow fever is quite suprizable.

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  15. It is a shame that the PAHO attempt to eliminate yellow fever failed, due to the fact that they had realized that there existed a jungle cycle of yellow fever. Understandably it was impossible to find and eliminate all the water niches that existed in the forest. So my question is, why not put in all that resource into vaccinating people in endemic area's? From what I have read, there is no known therapy in dealing with yellow fever. My question is even if they were to get this under control with vaccination would health professionals have to worry about different strains of the disease reappearing?

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    1. Sheaba Daniel

      I agree in that vaccination is the most effective strategy for preventing yellow fever. However, I am sure that there are several barriers that make high rates of YF vaccination difficult to achieve, such as lack of governmental commitment, poor management, and other financial/operational barriers.

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    2. In response to the previous post:
      There is no specific treatment for yellow fever. Treatment is symptomatic, aimed at reducing the symptoms for the comfort of the patient. Vaccination is the most important preventive measure against yellow fever.
      For patients not covered by health insurance, the cost of a yellow fever vaccination typically includes: a consultation fee, sometimes a fee to administer the shot, and the cost of the single required dose of vaccine. The total cost typically ranges from $150 to $350. For example, at the travel clinic operated by the San Francisco Department of Public Health, an initial consultation is $39, and the yellow fever vaccination costs $110, with no shot administration fee, for a total of $149.

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  16. It is frustrated to learn that the intensive vaccination campaign by PAHO was abandoned due to the identification of the jungle cycle. The abandonment of the program and the resurgence of A. aegypti in Southern America suggest that an effective public health intervention should be sustainable. Nevertheless, the program did successfully eliminate the urban cycle of yellow fever to a greater extent in Southern American countries. Therefore, it is certainly of strategic importance in eliminating the urban cycle of yellow fever in African countries from public health’s standpoint. Moreover, the success of the program in Southern America can serve as educational information to Africans who are usually reluctant to accept foreign assistance and intervention due to cultural and historical influence.

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  17. I have a couple of questions about this, especially in relation to Dengue. Since the same vector is responsible for large portions of the transmission of both diseases, is it possible for the same mosquito to transmit both at the same time...? In other words, can a person be bitten by A. Aegypti and contract both yellow fever and Dengue at the same time...?
    The other question: considering the lack of resources especially in terms of vaccine availability in many African countries, and given the high costs of the PAHO campaign, would it not be feasible to educate locals about the endemicity of yellow fever in their area (a fact that I'm sure they would already know, being in the community...? Employing local "medicine men", as well as other local resources (elders, etc) to help educate people about the mode of transmission (mosquitoes), the mosquitoes' dependence on water-containing vessels for their life cycles, and the possibility of breaking that cycle by reducing the availability of open vessels might serve to achieve results similar to those of PAHO. Of course I realize that it may prove difficult to remove all water-containing vessels, however, the use of lids may achieve the same results. Also, the campaign doesn't have to involve all of the nations affected immediately. In fact, it doesn't have to involve all of the villages affected immediately: you could start with an individual village, asking residents if they have any ideas as to how to eliminate the vessels while allowing for collection of rain water, etc. For example, making sure to close all vessels when they are not collecting water.

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    1. Wale, to answer your first question, I believe it is highly improbable for an A. aegypti mosquito to concurrently transmit yellow fever and dengue. Both flaviviruses could infect the mosquito. However, once the viruses are in the mosquito's body, the progression of the infection of each of these viruses might affect the course of the other infection. A virus's purpose is to replicate; and therefore, I believe that the presence of both viruses would cause mutual exclusion, or competition among the viruses. Also, there is a different genera of mosquitoes circulating yellow fever in rural Africa: A. africanus. Dengue is mainly transmitted by A. aegypti.

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    2. Co-infection is not only possible, but can be common in some settings. This can create a very dangerous situation with high morbidity and mortality.

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  18. The fact that evolution and human landscapes have essentially domesticated a type of mosquito is stunning to me. Aedes aegypti is no longer able to live in the forest an is solely a domestic arthropod. I feel this has many more implications than people may realize: it is constantly in close proximity with humans (its favorite hosts), it has the ability to house numerous different infections, it bites in the daylight, etc. This species has the potential to become even more lethal that it already is....

    However, it's domestication may also be its weakness. Since we know this mosquito will not be found (in large numbers) anywhere but the home, a widespread effective intervention could, hypothetically, wipe them all out and eliminate a major factor in numerous infections.

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    1. It is stunning and sad how we as the human population domesticated the mosquito and thus have brought harm onto our own species. But I do not agree with the domestication of the mosquito as also being its weakness. Rather maybe our presence is actually helping them thrive since we both need water and mosquitos are using us to fetch water for them essentially. This is because of the large human population and the difficulty of reaching all populations. I don't think there would be one effective widespread intervention. The PAHO attempt was a great attempt and it is unfortunate that it is no longer being used.

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  19. The evolutionary history of the mosquitoes is incredible. In a constantly changing environment where we are limiting the amount of jungle/natural habitat and increasing urban sprawl, it only make sense that the mosquitoes would evolutionarily adapt. While it is an ingenious adaptation, it makes for an easy control measure in highly endemic regions. If just eliminating small, water-bearing containers eliminates the breeding ground for mosquitoes and therefore eliminates a mode of transmission of the virus, that is a relatively easy control measure.

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  20. The main vectors of yellow fever are the Aedes aegypti mosquitoes, which are known to be the most domesticated mosquitoes in the world, since they have adapted ecology to the human domestic environment. As explained in the post, since this mosquito is “so very effective at exploiting the human environment, it is also very effective at transmitting any viruses that it is capable of carrying and which are infective to humans.” Yellow fever is distinct since it has three cycles of transmission: urban cycle, sylvan cycle, and intermediate cycle. It is scary to know that not only are some infections (i.e. areas where the virus is endemic) entirely asymptomatic but that it also has a high case-fatality, which is approximately 20% among populations where the disease is endemic and even as high as 90% among people from non-endemic areas. It is great to know that organizations and programs such as the PAHO program have been effective in eliminating A. aegypti. However, there are still places such as endemic African countries that do not have the necessary resources to mobilize widespread vaccination, which coupled with the added intermediate transmission cycle, has led to a higher disease burden in Africa. Furthermore, according to the CDC, a single dose of the yellow fever vaccine protects against disease for 10 years or more, however, if a person is at continued risk of infection, a booster dose is recommended every 10 years, which many people don’t have access to (2011).
    Works cited: http://www.cdc.gov/yellowfever/vaccine/index.html

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  21. The Aedes aegypti mosquitoes are vectors for a number of arboviruses, such as yellow fever and dengue fever. It's unfortunate that PAHO initiative to eradicate yellow fever was abandoned, even though it was later discovered as an impossible goal. I think it's still a worthwhile campaign, since the elimination of containers will aid in both limiting yellow fever and dengue fever cases. Especially since there is no vaccine for dengue fever and limited accessibility to yellow fever vaccines in Africa, I think this environmental campaign still holds value. I'm also curious if there is any research into making a combination vaccine for both yellow fever and dengue fever, since both are caused by Flaviviruses. However, according to the CDC, the yellow fever vaccine is a live virus, so maybe combining both into one vaccine may not be feasible or safe for people.

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    1. I would agree that that given the number of diseases (including emerging diseases such as the new strain of zika and perhaps future pathogens) for which mosquitoes are a vector, a large scale campaign such as that initiated in 1947 would be appropriate once again, even if reservoirs remain in the jungle cycle.
      One question about the PAHO campaign is whether any studies were done on the ecological effects of eradicating mosquitoes from large areas of their habitat. Did this affect the bat population, for example? If mosquitoes can be eradicated without damaging the food chains of urban and sylvan ecologies, I would strongly argue for a global eradication campaign with long term vigilance. Mosquito bites are at best annoying and itchy, at worst carriers of deadly pathogens.
      Standing water removal is likely the most effective way we currently have to embark on this campaign, but other ideas such as releasing sterile males into the environment may also hold promise.

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  22. It is interesting to learnt that rather than being born with the virus and acting as the sole reservoir, A. aegypti in fact gets "re-infected" with every new generation via mammals that are infected. Additionally, it was saddening to learn that the PAHO campaign fell apart after learning about the jungle cycle existence. This is something that puzzles me especially looking at it with a critical eye. Hindsight is always 20/20 but was no decrease in the prevalence of yellow fever detected during that time to display that the intervention is working? More so, eradicating one cycle by over 70% is a significant achievement being that most humans live in an urban environment and not the jungle. Thus, reducing the amount of urban infections should have made a substantial impact on the prevalence of the disease.
    On the map supplied by WHO displays that Florida is at risk for A. aegypti. What measures are taken there to prevent the spread of the vector and transmission of disease?

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  23. Jaundice causes a yellow discoloration in sufferers which provided the name for this disease: Yellow Fever. In turn, yellow fever gave the name to the flaviviruses.
    The current vaccine is very effective, but it is a live virus and relatively expensive. The outbreaks tend to occur in poor countries. The current outbreak in Angola highlights that the drop in the price of oil has directly affected the government’s ability to pay for a good vaccination program. This is worrying, not just for Yellow Fever but, if vaccines are not being administered, the country is also at high risk of seeing polio reemerge.

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