How did scientists figure out the Plasmodium life cycle?

Not one or two but the efforts of many over centuries led to the deciphering of the Plasmodium life cycle. Malaria histories point to Giovanni Maria Lancisi – Wikipedia, Charles Louis Alphonse Laveran – Wikipedia, Vasily Danilewsky – Wikipedia, Patrick Manson – Wikipedia, Ronald Ross – Wikipedia, Amico Bignami – Wikipedia, Giuseppe Bastianelli – Wikipedia, Angelo Celli – Wikipedia, Raimondo Feletti – Wikipedia, Giovanni Battista Grassi – Wikipedia, Camillo Golgi – Wikipedia and Ettore Marchiafava – Wikipedia as the most notable of these scientists.

This answer summarizes key discoveries related to the Plasmodium life cycle,

• How focus shifted from bad air to mosquitoes.
• How the Malaria causing organism was identified to be a protozoan, not bacterium.
• How the protozoan parasite gets into human blood in the first place.
• The role of the insect vector, mosquito, in transmitting Malaria between people.

What causes Malaria, Bad Air or Animalcule – Wikipedia?

Combining two Latin words, mal (bad) and aria (air), and originally written as ‘mal’aria’, obviously Malaria was associated with marsh air so much so that simply breathing it was for long thought sufficient to cause the disease. Ague, Cattivara, Intermittent fever, Paludism, Periodic Fever, Swamp miasmata, the various names used through history to describe this disease thus allude to two of its cardinal features, fever and proximity to swamps.

While speculating on the connection between swamps and Malaria epidemics in his 1717 treatise, De Noxiis Palodum Effloriis (On the Noxious Emanations of Swamps), the 17th century Italian physician, Giovanni Maria Lancisi, theorized that swamps produced two types of emanations, animate and inanimate, both potentially capable of causing Malaria. Africans and Indians had long recognized the link between Malaria and mosquitoes (2). Lancisi thus theorized animate emanations were mosquitoes that could carry Malaria-causing animalcules (1). Did such animalcules actually exist?

Are there Malaria causing organisms, and if yes, what are they? Bacteria or Protozoa?

Long before the discovery of the Malaria parasite, Plasmodium, careful observers had already discerned something different about the blood and often also the spleen and liver of Malaria patients. Specifically, autopsies showed some type of heavy pigmentation in these cells and organs. For example, Professor Joseph Jones of the University of Louisiana testified in an 1876 court case that (see below from 2)

‘certain stains on the coat and shirt of an accused prisoner were not paint, as had been affirmed, but were the blood ‘of a human being who had suffered and was probably suffering at the moment when the blood was abstracted, with malaria or paroxysmal fever…many of the particles of melanic pigment were spherical, others irregular and angular, some entirely free, others encased in a hyaline mass’

Today we know this pigment to be Hemozoin – Wikipedia, a product of Malaria parasite metabolism inside red blood cells.

Having already observed such pigmented cells in the autopsied tissues of Malaria patients as well as in fresh blood drawn from those known to have the disease, Charles Louis Alphonse Laveran, a French army physician posted to Constantine, Algeria, in 1878, was already determined to in his own words ‘follow the pigment‘ (3). Looking for pigment in fresh Malaria patient blood with the additional advantage of using a microscope objective with a maximum magnification of 400X, Laveran meticulously examined blood smears of 200 patients, and found in 148 not just the characteristic pigment associated with Malaria blood but also crescent-shaped ‘spherical motionless bodies with pigment, spherical moving bodies with pigment and bodies that extruded flagella-like structures‘ (3), reporting his breakthrough on 6 November 1880 thus (see below from 2),

‘I had suspected for a long time the parasitic nature of these bodies when on November 6th, 1880, while examining one of the spherical pigmented elements in a preparation of fresh blood, I noticed with joy at the periphery motile filaments [probably exflagellation] of the animated nature of which there was no room for doubt’

Laveran obviously (see below from 1)

‘was astonished to observe, [in a soldier’s blood specimen] . . . a series of fine, transparent filaments that moved very actively and beyond question were alive’

Laveran‘s key findings were (3)

• Crescent-shaped bodies present in blood smears of 148 Malaria patients but never in those without Malaria, and
• That Quinine removed these stages from the blood.

Realizing he’d found a parasitic protozoan, Laveran called it Oscillaria malariae and presented his findings to the French Academy of Medical Sciences in December 1880 (4). Though Laveran did win the Nobel Prize in 1907 for identifying the Malaria parasite as a protozoan, his discovery was without precedent since no protozoan had ever been reported inside a human blood cell and thus his findings were initially greeted with skepticism. After all this was the heyday of the bacterium and scientific luminaries such as Robert Koch – Wikipedia and Louis Pasteur – Wikipedia ruled the roost with their discovery of important disease causing bacteria.

Even the eminence grise of physicians, William Osler – Wikipedia, was skeptical at first and only became convinced by looking at blood smears of Malaria patients himself over several weeks (see below from 2).

‘When I first read Laveran’s papers nothing excited my incredulity more than his description of the ciliated bodies. It seemed so improbable and so contrary to all past experience, that flagellate organisms should occur in the blood…The work of the past six months has taught me a lesson on the folly of skepticism based on theoretical conceptions, and of pre-conceived notions drawn on limited experience’

Unknown to Laveran, the Russian physiologist, Vasily Danilewsky, had already discovered a number of parasites in the blood of birds and reptiles (3). Calling them ‘pseudovacules’, by 1885, Danilewsky had identified Plasmodium – Wikipedia, https://en.wikipedia.org/wiki/Ha… and https://en.wikipedia.org/wiki/Le…. Since most of his work was published in Russian, only the French publication of his 3-volume book, La Parasitologie Comparée du Sang, in 1889, made his discoveries widely known.

How the protozoan Malaria parasites get into patients’ blood in the first place: Discovery of the insect-to-human cycle

Laveran‘s discovery connected Malaria to a microscopic protozoan organism. However, how did the protozoan parasite get into Malaria patients’ blood in the first place?

A key figure in parasitic diseases, Scottish parasitologist Patrick Manson was born in Aberdeenshire, Scotland, in 1844, and practiced medicine in Formosa (now Taiwan), where he saw many cases of https://en.wikipedia.org/wiki/Fi…. While on leave in London in 1874, Manson searched the medical literature and found several reports of microfilariae in blood of filarial patients. While wondering how such parasites could spread from one person to another, Manson hit upon the notion of a bloodsucking insect. Back in Formosa, Manson researched and cross-referenced the distribution of bloodsucking insects with filariasis cases. He found mosquitoes to be the best fit. Manson then tried to carefully reconstruct the human-to-insect transmission cycle. First, he fed mosquitoes on active filarial patients and then dissected the mosquitoes at varying lengths of time. This way Manson was able to

• Identify filariae in mosquito gut post-human feeding.
• Observe filarial development and migration into mosquito thoracic muscle where they continued growing.

However, Manson erred in his final conclusion, thinking infected mosquitoes returned to die in water and that humans got accidentally infected after drinking infected water. Shortly afterward, https://en.wikipedia.org/wiki/Jo… in Australia and https://en.wikipedia.org/wiki/Ge… in England (in Patrick Manson‘s lab) independently proved that infected mosquitoes transmitted filaria into humans when they bit them to take their blood meal.

Following in Manson’s footsteps, in the final decade of the 19th century, studies of various tropical diseases were leading scientists to a common notion, that of an insect-to-human cycle (1, 2).

• While local Texas ranchers had long believed ticks were somehow responsible for spreading Texas cattle fever, https://en.wikipedia.org/wiki/Th… and F.L. Kilbourne finally proved that the local ‘hard tick’, https://en.wikipedia.org/wiki/Rh…, transmitted the parasite, https://en.wikipedia.org/wiki/Ba….
• Working in then-Zululand, https://en.wikipedia.org/wiki/Da… showed that https://en.wikipedia.org/wiki/Ts… transmitted nagana or https://en.wikipedia.org/wiki/An…. However, Bruce made a mistake, correct about how insects became infected from taking blood meal on an infected person/animal but incorrect in being unable to decipher that infected insect biting uninfected host could transmit disease back.
• While the Cuban epidemiologist, https://en.wikipedia.org/wiki/Ca…, had suggested mosquitoes might spread https://en.wikipedia.org/wiki/Ye…, there was no proof yet. Already back in 1804, observing that doctors and nurses who cared for yellow fever patients seemed to not get the disease, https://en.wikipedia.org/wiki/St… had subjected himself to some remarkable self-experiments by exposing himself to the ‘hemorrhagic vomitus, other excretions, and blood of patients dying of yellow fever‘ (1). Unable to transmit infections through these methods, Ffirth had concluded that yellow fever was not directly transmitted from person to person. During the 1898 https://en.wikipedia.org/wiki/Sp…, a yellow fever commission led by https://en.wikipedia.org/wiki/Wa… was tasked to investigate. Using human volunteers, the commission found yellow fever could be transmitted to humans by Stegomyia fasciata (now called Aedes aegypti) mosquitoes, with one volunteer Jesse W. Lazear (1866-1900) succumbing to yellow fever from a mosquito bite (5).

Though never awarded the Nobel prize, Manson‘s groundbreaking insight has led to him being labeled the ‘father’ of tropical medicine. Most importantly, Manson‘s observations of Malaria patients in London had shown him that flagellated forms of the Malaria parasite only appeared after blood taken from Malaria patients cooled, i.e., at a temperature far below that of human body temperature. From this he concluded other stages of parasite development occurred outside the human body, perhaps in mosquitoes. Thus, by the time British medical doctor Ronald Ross entered the picture, the time was ripe for connecting all the dots in the Malaria transmission cycle.

Meantime, by 1884 Laveran had convinced the leading Italian malariologists Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Giovanni Battista Grassi, Camillo Golgi, Ettore Marchiafava, as well as the ‘more cynical’ microbiologists Louis Pasteur, Charles Eouard Chamberland and Pierre Paul Emile Roux that Malaria was caused by a protozoan, not a bacterium (3). Only Robert Koch, perhaps the pre-eminent microbiologist of the time, still remained a holdout against the protozoa-Malaria idea.

Moving full speed ahead on their independent studies to decipher the role of mosquitoes in Malaria transmission set the British and Italians on a famous collision course where the rightful recognition for discovery became a casualty of politics.

Deciphering the role of the insect vector in Malaria transmission: Independent discovery by British and Italians

The British side of the Malaria story

Meeting Manson for the first time in 1894 when he was home in London on leave, Ross, then a low ranking physician in the Indian Medical Service, became his student. Convinced Malaria was spread by mosquitos and that India was the ideal place to finally crack the case, Manson taught Ross the basics, showing him human blood smears containing Malaria parasites.

With Manson supervising his studies long-distance, and heeding his dictate to ‘follow the flagellum‘ (3) over the next four years, Ross tried to connect the dots between Plasmodium, mosquitoes and Malaria. First, Ross fed different types of mosquitoes on Malaria patients. Ross had three different types of mosquitoes to choose from, common grey or barred-back, less common ‘brindled’, and much rarer ‘dappled-winged’ (3).

On two consecutive days in August 1897, Ross was fortunate to have supply of the rarer ‘mosquitoes whose wings were dappled and had four dark spots‘ (2). Today, we call such mosquitoes anopheline. After feeding such mosquitoes on a Malarial patient with crescent-shaped bodies in their red blood cells, Ross observed cysts growing on the mosquitoes’ stomachs, and that when these cysts ruptured, they released ‘rods’ that invaded the mosquitoes’ salivary glands. Indeed he found mosquito salivary glands to be packed with Plasmodium rods, a discovery he marked by calling August 20, 1897, ‘mosquito day’, a date that’s been commemorated as such ever since, https://en.wikipedia.org/wiki/Wo….

Unfortunately, before Ross could pursue the next logical step in the discovery process and experimentally show Malaria transmission from diseased to healthy people through the bite of Malaria-infected mosquito, he was transferred to Calcutta, a city with little human Malaria, to instead work on kala-azar, https://en.wikipedia.org/wiki/Vi…. Luckily, Manson had suggested to Ross the possibility of studying Malaria in birds as well. Thus, in Calcutta, Ross began work on Proteosoma relictum (now called Plasmodium relictum), a common Malaria parasite in crows and sparrows.

Here he found that rather than ‘dappled-winged’, the more common ‘grey’ (now called culicine) mosquitoes did the trick. Specifically, he found that 178 of 242 ‘grey’ mosquitoes fed on infected birds developed ‘pigmented spores’ (3). Ross was then able to follow all of the parasite’s developmental steps within the mosquito, from exflagellation and fertilization in its gut to oocyst formation and sporogony to final migration of sporozoites in its salivary glands (2). The final proof came when Ross could infect healthy sparrows by inoculating them with sporozoites isolated from experimentally infected mosquitoes.

Writing to Manson on July 6, 1898, Ross memorialized his discovery thus (see below from 1, emphasis mine),

‘I think that this, after further elaboration, will close at least one cycle of proteosoma, and I feel that I am almost entitled to lay down the law by direct observation and tracking the parasite step by step—Malaria is conveyed from a diseased person or bird to a healthy one by the proper species of mosquito and is inoculated by its bite. Remember, however, that there is virtue in the “almost.” I don’t announce the law yet. Even when the microscope has done its utmost, healthy birds must be infected with all due precaution. . . . In all probability it is these glands which secrete the stinging fluid which the mosquito injects into the bite. The germinal rods . . . pass into the ducts . . . and are thus poured out in vast numbers under the skin of the man or bird. Arrived there, numbers of them are probably instantly swept away by the circulation of the blood, in which they immediately begin to develop into malaria parasites, thus completing the cycle. No time to write more’

Manson presented these results to the British Medical Association in Edinburgh in July 1898 (1).

The Italian side of the Malaria story

In the 1890s, Italian scientists such as Bastianelli, Bignami, Golgi, Marchiafeva reported how the protozoan parasite invaded blood cells, grew within them, and produced daughter cells that invaded other blood cells (3). By 1898, Bignami and Grassi had access to Malaria sites in Rome and Siciliy. Over the next two years, the Italians methodically filled in the blanks (6, 7),

• Showed only female Anopheles mosquitoes could transmit Malaria.
• Described the entire lifecycle of Plasmodium vivax, P. falciparum and P. malariae. Feeding local Anopheles claviger mosquitoes on infected patients transmitted infection to uninfected individuals via the bite of such infected mosquitoes.
• In a classic experiment, Grassi sent 112 volunteers to a malarious region in the Capaccio Plains, protecting them from mosquito bites between dusk and dawn. Only 5 of these volunteers succumbed to Malaria compared to 415 unprotected volunteers, all of whom contracted it.

Thus, by 1898, Grassi, Bastianelli and Bignami had not only resolved the entire life cycle of the human Malaria parasite, Plasmodium falciparum, but also demonstrated that Malaria could not exist without Anopheles mosquito. Yet, only Ross was awarded the Nobel Prize for this discovery in 1902. Why this discrepancy? Politics, which is never pure nor simple (Nobel Prize controversies – Wikipedia).

This is when Robert Koch enters the picture, ostensibly at the invitation of the Italian government to ‘solve the malaria problem‘ (8). Apparently this is when the Italians rushed to publish their results, with Grassi first publishing his initial report on the P. falciparum lifecycle in November 1898, citing Ross‘ work only at the very end, and then publishing a fuller report a month later not citing Ross at all (2). Thus ensued a battle royale between Ross and Grassi with Koch apparently eagerly adding the kindling. Rich irony there that of all the world famous microbiologists of his time, Koch was perhaps the last to begrudgingly acknowledge only by 1887 that Malaria was caused not by a bacterium but by a protozoan. When the committee considered splitting the 1902 Nobel Prize between Ross and Grassi, it was apparently Koch‘s vehement opposition that led to the prize going to Ross alone (1), more proof, not that we need more, that human society rewards aren’t merit-based as a matter of course, even though we or at least some of us fervently wish they were.

Bibliography

1. Nelson, Kenrad E., et al. “Infectious disease epidemiology theory & practice.” (2001): 205.

2. Esch, Gerald. Parasites and Infectious disease: discovery by serendipity and otherwise. Cambridge University Press, 2007.

3. Cox, Francis EG. “History of the discovery of the malaria parasites and their vectors.” Parasites & vectors 3.1 (2010): 5. https://parasitesandvectors.biom…

4. Laveran, Alphonse. Un nouveau parasite trouvé dans le sang des malades atteints de fièvre palustre: origine parasitaire des accidents de l’impaludisme. 1881.

5. Reed, Walter, and James Carroll. “The prevention of yellow fever.” Public health papers and reports 27 (1901): 113. https://www.ncbi.nlm.nih.gov/pmc…

6. Grassi, Battista, Amico Bignami, and Giuseppe Bastianelli. Ulteriori ricerche sul ciclo dei parassiti malarici umani nel corpo del zanzarone. tip. della R. Accademia dei Lincei, 1898.

7. Grassi, Giovanni Battista. Studio di uno zoologo sulla malaria. Vol. 3. R. Accademia dei lincei, 1900.

8. Harrison, Gordon. “Mosquitoes, malaria and man: a history of the hostilities since 1880.” Mosquitoes, malaria and man: a history of the hostilities since 1880. (1978).

https://www.quora.com/How-did-scientists-figure-out-the-Plasmodium-life-cycle/answer/Tirumalai-Kamala

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How did the Zika virus get to the US?

A Vector (epidemiology) – Wikipedia -borne disease spread by bites of infected Aedes – Wikipedia species, Zika’s recent trajectory suggests it was only a matter of time before it got to the US.

This is because

• Its most prominent vector, Aedes aegypti – Wikipedia, is widespread across the southern US (1).

• Locally infected mosquitoes sustain local Zika infection (see below from 2).

Little known for 60 years since its original isolation from a monkey in Zika forest in Uganda in 1947, < 20 human cases of Zika infection were confirmed over the next 60 years (3). However, a quick succession of outbreaks across Polynesia, first in Yap island in 2007 then in French Polynesia in 2013, suggested Zika had somehow quietly spread beyond Africa sometime during those decades. 2015-2016 outbreaks in Brazil and Colombia signaled it had spread to the Americas (see below from 2 and 4).

Keep in mind, Zika could keep coming to the US through other means as well. While it was primarily considered mosquito-borne, data from these successive large-scale outbreaks showed that it could also be transmitted sexually, vertically (from mother to fetus) and through blood (2). This means that some degree of local infection could be sustained by returning infected travelers as well. After all, sexual transmission was suspected in what was perhaps the very first documented case of Zika infection in mainland US all the way back in 2008, when a US researcher, infected while working in the field in Senegal, apparently infected his wife but not his children after he returned to the US (5).

Bibliography

1. http://www.usd338.com/vimages/sh…

2. Basu, Rupsa, and Ebenezer Tumban. “Zika Virus on a Spreading Spree: what we now know that was unknown in the 1950’s.” Virology journal 13.1 (2016): 165. https://virologyj.biomedcentral….

3. Musso, Didier, and Duane J. Gubler. “Zika virus.” Clinical microbiology reviews 29.3 (2016): 487-524. Zika Virus

4. Baud, David, et al. “An update on Zika virus infection.” The Lancet.

5. Foy, Brian D., et al. “Probable non–vector-borne transmission of Zika virus, Colorado, USA.” Emerging infectious diseases 17.5 (2011): 880. https://www.ncbi.nlm.nih.gov/pmc…

https://www.quora.com/How-did-the-Zika-virus-get-to-the-US/answer/Tirumalai-Kamala

Is there any evidence that the Zika virus hurts the brain development of infants or young children if they’re infected after they’re born?

Tags

Microcephaly

Most reported Zika-associated microcephaly cases are from intrauterine first trimester infection. Among perinatal, specifically third trimester and immediate post-birth, Zika cases, there are only a few case reports of brain development issues.

Reported Outcomes Of Perinatal Zika Infection

Though a mouse model of Zika infection (1), where embryos were infected in utero at embryonic age 14.5 days (mouse gestation is ~21 days), reported post-natal microcephaly, only a handful of human perinatally infected Zika-associated brain development or neurologic issues have been reported in the biomedical literature so far.

• Reported Brain And/Or Neurologic Abnormalities
  • Two infants with laboratory-confirmed Zika infection from third trimester exposure during the 2016-16 Brazil Zika outbreak showed not microcephaly but other brain abnormalities such as subependymal cysts in both and lenticulostriate vasculopathy in one (2).
  • Paraguay reported Guillain–Barré syndrome – Wikipedia in one child after post-natal Zika in 2016 (3).
• No Reported Brain And/Or Neurologic Abnormalities
  • Of two cases of perinatal Zika transmission from mothers infected close to delivery during the 2013-14 French Polynesia Zika outbreak, one infant remained asymptomatic while the other was diagnosed with Thrombocytopenia – Wikipedia and diffuse rash but not microcephaly (4).
  • A study (5) of 1501 live births of Zika-infected mothers during the 2015-16 Brazil Zika outbreak found first trimester infection to be most severely affected, based on head circumference z score.
  • Similarly, no apparent anomalies were reported (6) among children born to 1850 pregnant women in Colombia, >90% of them reportedly Zika infected during the third trimester.

Reported Outcomes Of Postnatal Zika Infection In Infants & Children

• The CDC collated and analyzed (7) previously published data (8, 9, 10, 11, 12, 13) on ten 3 to 16 year old Zika-infected children from Africa, Asia, South America and the Pacific. Though none of them developed rash, all had fever, 2 each had conjunctivitis, vomiting or diarrhea while 3 had joint pain (Arthralgia – Wikipedia). No microcephaly.
• All eight cases of travel-related Zika cases among American children as of February 2016 (7) had rash with at least one other symptom (fever, arthralgia, nonpurulent conjunctivitis). Again no microcephaly.
• The 2007 Yap Island, Micronesia Zika virus outbreak included several infants and children. While their symptoms were similar to those in adults, namely, fever, maculopapular rash, arthralgia, Conjunctivitis – Wikipedia, 0 to 19 year olds had fewer probable and confirmed cases of Zika compared to 20 to 59 year olds (14). No microcephaly.
• No single case of microcephaly reported to CDC from US states among 150 probable or confirmed Zika cases among children <18 years of age (15). Ranging from 1 month to 17 years in age with median age of 14 years, all infections were travel-associated.
  • 129 (82%) had rash.
  • 87 (55%) had fever.
  • 45 (29%) had conjunctivitis.
  • 44 (28%) had arthralgia.

Bibliography

1. Shao, Qiang, et al. “Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage.” Development 143.22 (2016): 4127-4136.

2. de Souza, Antonio Soares, et al. “Fetal infection by Zika virus in the third trimester: report of 2 cases.” Clinical Infectious Diseases 63.12 (2016): 1622-1625.

3. Lovera, Dolores, et al. “Neurologic syndrome associated with Zika postnatal acquisition. With regard to the first case in Paraguay.” Revista del Instituto de Medicina Tropical 11.2 (2016): 36-41.

4. Besnard, M., et al. “Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014.” Euro surveill 19.13 (2014): 20751. http://www.eurosurveillance.org/…

5. França, Giovanny VA, et al. “Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation.” The Lancet 388.10047 (2016): 891-897. https://www.researchgate.net/pro…

6. Pacheco, Oscar, et al. “Zika virus disease in Colombia—preliminary report.” New England Journal of Medicine (2016). http://www.nejm.org/doi/pdf/10.1…

7. Fleming-Dutra, Katherine E. “Update: interim guidelines for health care providers caring for infants and children with possible Zika virus infection—United States, February 2016.” MMWR. Morbidity and mortality weekly report 65 (2016). https://www.cdc.gov/mmwr/volumes…

8. Macnamara, F. N. “Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria.” Transactions of the royal society of tropical medicine and hygiene 48.2 (1954): 139-145. http://icmr.nic.in/zika/publicat…

9. Olson, J. G., and T. G. Ksiazek. “Zika virus, a cause of fever in Central Java, Indonesia.” Transactions of the Royal Society of Tropical Medicine and Hygiene 75.3 (1981): 389-393. http://www.dtic.mil/cgi-bin/GetT…

10. Heang, Vireak. “Zika Virus Infection, Cambodia, 2010-Volume 18, Number 2—February 2012-Emerging Infectious Disease journal-CDC.” (2012). https://www.ncbi.nlm.nih.gov/pmc…

11. Alera, Maria Theresa, et al. “Zika virus infection, Philippines, 2012.” Emerging infectious diseases 21.4 (2015): 722. https://www.ncbi.nlm.nih.gov/pmc…

12. Dupont-Rouzeyrol, Myrielle. “Co-infection with Zika and Dengue Viruses in 2 Patients, New Caledonia, 2014-Volume 21, Number 2—February 2015-Emerging Infectious Disease journal-CDC.” (2015). https://www.researchgate.net/pro…

13. Arzuza-Ortega, Laura, et al. “Fatal sickle cell disease and Zika virus infection in girl from Colombia.” Emerging infectious diseases 22.5 (2016): 925. https://www.ncbi.nlm.nih.gov/pmc…

14. Duffy, Mark R., et al. “Zika virus outbreak on Yap Island, federated states of Micronesia.” N Engl J Med 2009.360 (2009): 2536-2543. http://www.nejm.org/doi/pdf/10.1…

15. Goodman, Alyson B. “Characteristics of Children Aged< 18 Years with Zika Virus Disease Acquired Postnatally—US States, January 2015–July 2016.” MMWR. Morbidity and Mortality Weekly Report 65 (2016). https://www.cdc.gov/mmwr/volumes…

https://www.quora.com/Is-there-any-evidence-that-the-Zika-virus-hurts-the-brain-development-of-infants-or-young-children-if-theyre-infected-after-theyre-born/answer/Tirumalai-Kamala

Should blood banks be testing for Zika?

Tags

Blood bank, Blood test, Blood transfusion

Recent data suggest blood transfusions could transmit Zika so yes, blood banks in Zika-endemic areas should test for it. The link between maternal Zika infection and baby microcephaly (1) and other serious birth defects (2) is now compelling. Were Zika-infected blood transfused to pregnant women, risk could be unacceptably high for fetuses.

Though Zika fever is a Vector (epidemiology) -borne disease spread by the bite of infected Aedes mosquitoes, a steady drumbeat of data shows it can also spread by other routes.

Zika persists in semen (3, 4), vaginal tract (5, 6) and in circulation of pregnant women (7) for surprisingly long periods of time, and can be transmitted sexually (8, 9, 10, 11). Since Zika’s asymptomatic in ~80% of those infected, Zika-infected blood transfusions could be a risk factor to fetuses not just if given to pregnant women but also if given to their sexual partners.

Preliminary data suggest blood transfusion could transmit Zika

• During the 2013-2014 French Polynesia Zika virus outbreak it was detected by Reverse transcription polymerase chain reaction (RT-PCR) in 42 of 1505 (2.8%) blood donors who were asymptomatic when they donated (12). 11 of these 14 reported having Zika fever-like syndrome about 3 to 10 days later.
• In the US territory of Puerto Rico, a total of 68 of 12777 (~0.5%) blood donations from April 3 to June 11, 2016 were identified as presumptive Zika viremic based on Nucleic acid test (NAT) with rates rising by ~2.2 over a 9 week period during the summer (see figure below from 13).

These studies revealed Zika’s potential for spreading through blood transfusion.

More recently, a couple of case reports suggest blood transfusions could indeed transmit Zika

• In Brazil (14), concentrated Platelet from the blood of an asymptomatic 54 year old man was transfused into a 55 year old liver cancer patient undergoing liver transplant.
  • Four days post-transplant, the transfused recipient was serum Zika virus positive by RT-PCR.
  • Suspicion fell on the platelet donor after he contacted the blood donor facility 3 days after his donation to report he’d just developed dengue-like symptoms. His stored serum sample was then tested and found positive not for Dengue but for Zika virus by RT-PCR.
  • Though source of recipient’s Zika could have been other transplant related tissues and blood products, sequence analysis of 10 partial nucleotide sequences of the Zika virus isolated from the donor compared with the complete genome sequence of that isolated from the recipient matched 99.8%, strongly suggesting Zika transmission through transfusion.
  • Recipient coming from a Zika non-epidemic area and being hospitalized in a mosquito-free area for 5 days before his Zika positive test further increased the likelihood he got Zika from his platelet transfusion.

• In Brazil again (15), an asymptomatic person donated platelets through Apheresis on January 16, 2016. These were transfused into two different patients on January 19.
  • On January 21, the donor called the blood bank to report Zika symptoms (skin rash, eye pain, pain in both knees) starting on January 18.
  • Donor samples before and after donation were negative for related Dengue virus and Chikungunya by RT-PCR. However, donor’s plasma and urine samples were Zika positive 14 days after initial blood donation.
  • Plasma samples from both recipients were Zika positive, 6 and 23 days post-transfusion, respectively.

Given the high risk of newborn microcephaly from maternal Zika infection, far better to err on the side of caution and start screening blood donations for Zika. This may be why on August 26, 2016, the US FDA (16, emphasis mine)

‘issued a revised guidance recommending universal testing of donated Whole Blood and blood components for Zika virus in the U.S. and its territories‘.

Based on the available evidence the FDA concluded (17)

‘ZIKV meets the conditions for an RTTI [relevant transfusion-transmitted infection ] as described in 21 CFR 630.3(h)(2)‘

Specifically (17, emphasis mine),

‘FDA has determined that ZIKV meets the criteria in 21 CFR 630.3(h)(2) for an RTTI because of the sufficient incidence and prevalence of ZIKV to affect the potential donor population in the United States and because of the availability of appropriate screening tests for ZIKV‘ .

Bibliography

1. Johansson, Michael A., et al. “Zika and the Risk of Microcephaly.” New England Journal of Medicine (2016). http://www.nejm.org/doi/pdf/10.1…

2. Rasmussen, Sonja A., et al. “Zika virus and birth defects—reviewing the evidence for causality.” New England Journal of Medicine 374.20 (2016): 1981-1987. http://www.nejm.org/doi/pdf/10.1…

3. Mansuy, Jean Michel, et al. “Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen.” Lancet Infect Dis 16.405 (2016): 00138-9. https://www.researchgate.net/pro…

4. Barzon, L., et al. “Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016.” Euro surveillance: bulletin Européen sur les maladies transmissibles= European communicable disease bulletin 21.32 (2016). http://www.eurosurveillance.org/…

5. Davidson, Alexander. “Suspected female-to-male sexual transmission of Zika virus—New York City, 2016.” MMWR. Morbidity and Mortality Weekly Report 65 (2016). http://www.cdc.gov/mmwr/volumes/…

6. Prisant, N. et al. Zika virus in the female genital tract. Lancet Infectious Diseases, 2016, July 11. http://www.thelancet.com/pdfs/jo…

7. Meaney-Delman, Dana, et al. “Prolonged Detection of Zika Virus RNA in Pregnant Women.” Obstetrics & Gynecology (2016). Prolonged Detection of Zika Virus RNA in Pregnant Women. : Obstetrics & Gynecology

8. Foy, Brian D., et al. “Probable non-vector-borne transmission of Zika virus, Colorado, USA.” Emerg Infect Dis 17.5 (2011): 880-2. https://www.researchgate.net/pro…

9. Coelho, Flávio Codeço, et al. “Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil.” bioRxiv (2016): 055459. http://www.biorxiv.org/content/b…

10. D’Ortenzio, Eric, et al. “Evidence of sexual transmission of Zika virus.” New England Journal of Medicine 374.22 (2016): 2195-2198. http://www.nejm.org/doi/pdf/10.1…

11. Fréour, Thomas, et al. “Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016.” Eurosurveillance 21.23 (2016). http://www.e-sciencecentral.org/…

12. Musso, D., et al. “Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014.” Euro Surveill 19.14 (2014): 20761. http://www.eurosurveillance.org/…

13. Kuehnert, Matthew J. “Screening of blood donations for Zika virus infection—Puerto Rico, April 3–June 11, 2016.” MMWR. Morbidity and Mortality Weekly Report 65 (2016). https://www.cdc.gov/mmwr/volumes…

14. Barjas‐Castro, Maria L., et al. “Probable transfusion‐transmitted Zika virus in Brazil.” Transfusion 56.7 (2016): 1684-1688. http://onlinelibrary.wiley.com/d…

15. Motta, Iara JF, et al. “Evidence for Transmission of Zika Virus by Platelet Transfusion.” New England Journal of Medicine (2016). http://www.nejm.org/doi/pdf/10.1…

16. FDA advises testing for Zika virus in all donated blood and blood components in the US

17. http://www.fda.gov/downloads/Bio…

https://www.quora.com/Should-blood-banks-be-testing-for-Zika/answer/Tirumalai-Kamala

If a child is conceived while the father has Zika, but the mother never gets infected, can the fetus be affected?

Tags

Sexual transmission

Though bite of infected Aedes – Wikipedia mosquito is its primary mode of spread, since 2011, several case reports have

• Suggested Zika can be sexually transmitted.
• Documented Zika’s prolonged presence in semen of infected men.

In August 2016, the WHO (1) listed a total of 17 published reports on possible sexual transmission of Zika and 8 others on its presence in semen. Thus, as of Oct 2016, there’s plenty of scientific evidence that it’s possible for a Zika-infected man to infect a previously uninfected woman during sexual intercourse, in which case a fetus could also be affected. In other words, counting on a woman remaining uninfected following sex with a Zika-infected man is highly risky, especially for the fetus.

Reports Of Sexual Transmission From Symptomatic Males To Females

In each of these cases, the previously uninfected women developed symptoms suggestive of Zika even though they hadn’t been exposed to Zika-infected mosquitoes, i.e., highly likely they were infected through sexual transmission.

Cases reported from Argentina and France (2), Canada (3), Chile (4), France, where in one case the suspected route was oral sex (5) while the other case suggested male to female sexual transmission occurred 32 to 41 days after the man got infected with Zika (6), Germany (7), Italy (8), a case where Zika virus RNA was found in the man’s semen even 62 days after first symptoms of infection, New Zealand (9), a case where semen samples from the man tested positive for Zika virus RNA even 76 days after symptom onset and only tested negative on days 99 and 117, Peru (10), Spain (11), USA (12, 13, 14, 15).

Other Reports Of Sexual Transmission Include

• Asymptomatic male to female, one each in France (16) and USA (17). Since ~80% of Zika-infected people remain asymptomatic (18), prolonged presence of potentially infectious Zika in semen makes its sexual transmission a very important means of spreading through the population. Data also shows a pregnant woman being asymptomatic doesn’t preclude Zika virus from affecting the fetus.
• One case of male to male transmission (anal sex), in Texas, USA (19).
• One case of female to male transmission in New York City, USA (20).

Documented Cases Of Zika’s Presence In Semen

Live virus: Researchers were able to isolate Zika virus from semen

• In one case from the 2013 French Polynesia – Wikipedia Zika outbreak (21) two weeks after self-reported symptoms started.
• In a French case where semen virus load was 100000 times that in blood (22) two weeks after self-reported symptoms started.
• Even 62 days after first fever symptom in a case from Scotland (23).

Virus RNA: Detectable in a Netherlands patient up to 47 days after symptom onset (24), 80 (25) and 93 days (26) from two cases in France, and even 181 (27) and 188 days (28) in two cases from Italy.

These data suggest live virus is not only present in semen of Zika-infected men but can also stay there for extended periods of time. This is why the WHO recommends (1) that

• In regions with active Zika virus transmission,

‘Pregnant women should practice safer sex or abstain from sexual activity for at least the whole duration of the pregnancy. Their partners should also be informed about this recommendation.’

• And in regions with no active Zika virus transmission,

‘a. Men and women returning from areas where transmission of Zika virus is known to occur should adopt safer sex practices or consider abstinence for at least 6 months upon return to prevent Zika virus infection through sexual transmission.

b. Couples or women planning a pregnancy, who are returning from areas where transmission of Zika virus is known to occur, are advised to wait at least 6 months before trying to conceive to ensure that possible Zika virus infection has cleared.

c. Sexual partners of pregnant women, returning from areas where transmission of Zika virus is known to occur, should be advised to practice safer sex or abstain from sexual activity for at least the whole duration of the pregnancy.’

Bibliography

1. World Health Organization. “Prevention of sexual transmission of Zika virus: interim guidance update.” World Health Organization, Geneva, Switzerland (2016). http://apps.who.int/iris/bitstre…

2. Zika virus infection – Argentina and France

3. Statement from the Chief Public Health Officer of Canada and Ontario’s Chief Medical Officer of Health on the first positive case of sexually transmitted Zika Virus – Canada News Centre

4. Zika virus infection – Chile

5. D’Ortenzio, Eric, et al. “Evidence of sexual transmission of Zika virus.” New England Journal of Medicine 374.22 (2016): 2195-2198. http://www.nejm.org/doi/pdf/10.1…

6. Turmel, Jean Marie, et al. “Late sexual transmission of Zika virus related to persistence in the semen.” The Lancet (2016). http://ac.els-cdn.com/S014067361…

7. Frank, Christina, et al. “Sexual transmission of Zika virus in Germany, April 2016.” Eurosurveillance 21.23 (2016). http://www.eurosurveillance.org/…

8. Venturi, G., et al. “An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014.” Euro Surveill 21.8 (2016): 30148. http://www.eurosurveillance.org/…

9. Harrower, Jay, et al. “Sexual transmission of Zika virus and persistence in semen, New Zealand, 2016.” Emerging Infectious Diseases 22.10 (2016): 1855. http://wwwnc.cdc.gov/eid/article…

10. Zika virus infection – Peru

11. Spain records first case of sexually transmitted Zika virus

12. Foy, Brian D., et al. “Probable non–vector-borne transmission of Zika virus, Colorado, USA.” Emerging infectious diseases 17.5 (2011): 880. http://www.ncbi.nlm.nih.gov/pmc/…

13. Sex After a Field Trip Yields Scientific First. Martin Enserink, Science, April 6, 2011. Sex After a Field Trip Yields Scientific First

14. Zika Infection Transmitted by Sex Reported in Texas. The New York Times, Donald G. McNeil Jr., Sabrina Tavernise, Feb 2, 2016. Log In – New York Times

15. Hills, Susan L. “Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—continental United States, 2016.” MMWR. Morbidity and mortality weekly report 65 (2016). http://www.cdc.gov/mmwr/volumes/…

16. Fréour, Thomas, et al. “Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016.” Eurosurveillance 21.23 (2016). http://www.eurosurveillance.org/…

17. Brooks, Richard B. “Likely sexual transmission of Zika virus from a man with no symptoms of infection—Maryland, 2016.” MMWR. Morbidity and Mortality Weekly Report 65 (2016). http://www.cdc.gov/mmwr/volumes/…

18. Duffy, Mark R., et al. “Zika virus outbreak on Yap Island, federated states of Micronesia.” New England Journal of Medicine 360.24 (2009): 2536-2543. http://www.nejm.org/doi/pdf/10.1…

19. Deckard, D. Trew. “Male-to-male sexual transmission of Zika virus—Texas, January 2016.” MMWR. Morbidity and mortality weekly report 65 (2016). https://www.cdc.gov/mmwr/volumes…

20. Davidson, Alexander. “Suspected female-to-male sexual transmission of Zika virus—New York City, 2016.” MMWR. Morbidity and mortality weekly report 65 (2016). http://www.cdc.gov/mmwr/volumes/…

21. Musso, Didier, et al. “Potential sexual transmission of Zika virus.” Emerg Infect Dis 21.2 (2015): 359-61. https://www.researchgate.net/pro…

22. Mansuy, Jean Michel, et al. “Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen.” Lancet Infect Dis 16.405 (2016): 00138-9. https://www.researchgate.net/pro…

23. Atkinson, Barry, et al. “Detection of Zika virus in semen.” Emerg Infect Dis 22.5 (2016). Emerging Infectious Disease journal

24. Reusken, Chantal, et al. “Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016.” Eurosurveillance 21.23 (2016). http://www.eurosurveillance.org/…

25. Matheron, Sophie, et al. “Long-lasting persistence of Zika virus in semen.” Clinical Infectious Diseases 63.9 (2016): 1264-1264. Long-Lasting Persistence of Zika Virus in Semen

26. Mansuy, Jean Michel, et al. “Zika virus in semen of a patient returning from a non-epidemic area.” The Lancet Infectious Diseases 16.8 (2016): 894-895. http://www.thelancet.com/pdfs/jo…

27. Barzon, Luisa, et al. “Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016.” Eurosurveillance 21.32 (2016). http://www.eurosurveillance.org/…

28. Nicastri, Emanuele, et al. “Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016.” Eurosurveillance 21.32 (2016). http://www.eurosurveillance.org/…

 

https://www.quora.com/If-a-child-is-conceived-while-the-father-has-Zika-but-the-mother-never-gets-infected-can-the-fetus-be-affected/answer/Tirumalai-Kamala

What are the chances that there’s something else like Zika coming soon?

Tags

Aedes, Zoonosis

Global Zika-like outbreaks are increasingly inevitable largely due to unprecedented rates of

• Population mobility and density
• Rapid global transport
• Human ecosystem alteration
• Climate change

existing cheek by jowl with

• Vast health and wealth disparities
• Vast global differences in public health infrastructure including sanitation and active disease surveillance capacity
• Surfeit of neglected and/or little known diseases, many of them tropical, that lack drugs or vaccines to treat or prevent them and whose geographic reach spreads as climate change expands the range of the vectors capable of transmitting them.

Several of these factors also increase human-wildlife interactions, which in turn increase risk of Zoonosis – Wikipedia, diseases transmissible between animals and humans.

Originally discovered in 1947 in the Zika forest adjacent to Lake Victoria in Uganda, for decades Zika was but one of several RNA viruses known only to a handful of aficionados. Its obscurity began changing starting in 2007 when it caused an outbreak on the Micronesian island of Yap (1) followed by a larger 2013-2014 outbreak in French Polynesia (2) culminating of course in the global headlines of the 2015-2016 outbreak in Brazil and beyond (3).

So, clearly a case of a virus that until quite recently remained confined to a remote African forest and yet in less than a decade it’s spread across the globe, not only infecting large swaths of previously unexposed human populations but also expanding its capability in terms of disease outcomes from GBS (Guillain–Barré syndrome – Wikipedia) to fetal abnormalities (Microcephaly – Wikipedia). While less than a decade may sound shocking, not being unprecedented is even more so since Zika’s only following in the footsteps of related viruses, Chikungunya – Wikipedia and Dengue virus – Wikipedia, all zoonoses. Having similarly triumphantly marched across the globe in recent decades, their spread eerily echoes that of their carrier mosquito, Aedes – Wikipedia.

A 2008 study (4) estimated 335 emerging infectious diseases (EID) between 1940 and 2004. Averaging yields a very deceptive ~5 per year, deceptive because frequency between Pandemic – Wikipedia has steadily shrunk in recent years. Consider for example the high-profile global outbreaks of SARS (Severe acute respiratory syndrome – Wikipedia) in 2003, Bird flu (Influenza A virus subtype H5N1 – Wikipedia) in 2007, Swine flu (2009 flu pandemic – Wikipedia) in 2009, MERS (Middle East respiratory syndrome – Wikipedia) in 2012, Ebola virus disease – Wikipedia in 2014 and Zika fever – Wikipedia in 2015.

~60% of EIDs are primarily zoonotic. For e.g., Chikungunya, Dengue Ebola, HIV, Lyme, SARS, West Nile, Zika, to mention just a few.

• The 2008 analysis (4) concluded majority arose from wildlife and that human population density was the single common predictor for all types of EIDs (zoonotic or not, drug-resistant or not, vector-borne or not).
• EIDs seem to be a ‘hidden’ cost of human economic development (see below from 4, 5).

Population Mobility & Rapid Global Transport

Practically anywhere in the world is today a mere plane ride away even as these anywheres remain vastly different in basic public health infrastructure and active disease surveillance capacity. One sick person is all it takes for infectious diseases to spread beyond borders, i.e., vastly expanded potential for diseases to rapidly spread globally.

Consider for example how global air travel has exponentially expanded in <100 years. A paltry 1205 total global plane tickets sold in 1914 had increased to a whopping 2,595,448,927 in 2010. Yet large swaths of the world still lack adequate sanitation (see below from 6 and 7).

Human-driven Ecosystem Alterations & Climate Change Tilt The Balance In Favor Of Increased Pandemic Risk

More than ever before, massive human -driven ecosystem alterations have become the norm since the Industrial Revolution – Wikipedia with this process only further globalizing in the current era (8; see below from 9, emphasis mine).

‘With roughly half the temperate and tropical forests cut down, nearly half the icefree, desert-free terrestrial landscape converted to croplands or pasture, and more than 800,000 dams impeding the flow through more than 60% of the world’s rivers, alterations to our planet’s land use and land cover represent some of the most pervasive changes humanity has made to Earth’s natural systems‘

Human-driven ecological changes increase human encroachments into wildlife habitat. Such human-wildlife interactions increase zoonoses risk.

• For example, studies suggest such processes may have kick-started the initial Ebola and HIV outbreaks (10).
• No surprise then that ~75% of EIDs are zoonoses (4, 5, 11).
• New disease outbreaks become more inevitable when previously unimaginable mobility and enormous human-driven ecological changes exist alongside crippling poverty consisting of acute food scarcity and no sanitation, hygiene or running water since the more malnourished are weaker and likelier to get sick, especially with new EIDs.
• A corollary is increased hunting and consumption of wild meat, Bushmeat – Wikipedia (12).
  • For example, ‘ground zero’ for the 2013-2016 West African Ebola outbreak is suspected to be hungry children living in the remote Meliandou – Wikipedia village in southern Guinea – Wikipedia who killed and ate infected fruit bats (13, 14).
  • Something so seemingly inconsequential and yet it triggered a global public health emergency with a total of 28616 cases and 11310 fatalities from 10 countries according to West African Ebola virus epidemic – Wikipedia.
• Mapping such outbreaks only emphasizes that infectious disease transmissions have become that much easier given how fluidly, rapidly and easily humans can traverse the globe these days, and the increasingly porous divides between previously more strongly demarcated divisions such as affluence and poverty, sanitation and filth.

Thus, since lack of hygiene, sanitation and running water are today only a plane ride away so is pandemic risk.

The rapid, global expansion of mosquito species such as Aedes aegypti – Wikipedia and Aedes albopictus – Wikipedia is but one example of how climate change effects place greater selection pressures on vast numbers of species to adapt to these rapid changes, many of which end up increasing infectious disease risk not just in humans but for all types of life forms (see some other examples below from 15).

A 2009 analysis (16) concluded climate change may influence different arthropod-transmitted Arbovirus – Wikipedia diseases differently.

• Chikungunya: A single mutation in the Chikungunya virus facilitated its adaptation to the fast expanding mosquito species, A. albopictus, i.e., Chikungunya’s spreading by latching on to this mosquito’s coat-tails, whose spread is facilitated by climate change. Human travel simply augments spread even more.
• Rift Valley fever – Wikipedia, Bluetongue disease – Wikipedia: According to these authors, climate change helps mosquitoes spread in newly flooded areas while human activities such as irrigation projects, movements of herded animals and animal imports to feed large numbers of humans, for example during Mecca pilgrimages, also contribute to Rift Valley virus outbreaks.

Bibliography

1. Duffy, Mark R., et al. “Zika virus outbreak on Yap Island, federated states of Micronesia.” New England Journal of Medicine 360.24 (2009): 2536-2543. http://www.nejm.org/doi/pdf/10.1…

2. Cao-Lormeau, V. M., et al. “Zika virus, French polynesia, South pacific, 2013.” Emerging infectious diseases 20.6 (2014): 1085-1086. http://wwwnc.cdc.gov/eid/article…

3. Campos, Gubio S., Antonio C. Bandeira, and Silvia I. Sardi. “Zika virus outbreak, Bahia, Brazil.” Emerging infectious diseases 21.10 (2015): 1885. https://www.ncbi.nlm.nih.gov/pmc…

4. Jones, Kate E., et al. “Global trends in emerging infectious diseases.” Nature 451.7181 (2008): 990-993.

5. World Organisation for Animal Health

6. In flight

7. Total population: access to sanitation

8. Foley, Jonathan A., et al. “Global consequences of land use.” science 309.5734 (2005): 570-574. https://www.researchgate.net/pro…

9. Myers, Samuel S., et al. “Human health impacts of ecosystem alteration.” Proceedings of the National Academy of Sciences 110.47 (2013): 18753-18760. https://www.researchgate.net/pro…

10. Hahn, Beatrice H., et al. “AIDS as a zoonosis: scientific and public health implications.” Science 287.5453 (2000): 607-614. https://www.researchgate.net/pro…

11. Taylor, Louise H., Sophia M. Latham, and E. J. Mark. “Risk factors for human disease emergence.” Philosophical Transactions of the Royal Society of London B: Biological Sciences 356.1411 (2001): 983-989. http://rstb.royalsocietypublishi…

12. Wolfe, Nathan D., et al. “Naturally acquired simian retrovirus infections in central African hunters.” The Lancet 363.9413 (2004): 932-937. http://www.jhsph.edu/research/af…

13. Vogel, Gretchen. “Bat-filled tree source of Ebola epidemic?.” Science 347.6218 (2015): 142-143. Bat-filled tree may have been ground zero for the Ebola epidemic

14. Bausch, Daniel G., and Lara Schwarz. “Outbreak of Ebola virus disease in Guinea: where ecology meets economy.” PLoS Negl Trop Dis 8.7 (2014): e3056. http://journals.plos.org/plosntd…

15. Altizer, Sonia, et al. “Climate change and infectious diseases: from evidence to a predictive framework.” science 341.6145 (2013): 514-519. http://www.colorado.edu/eeb/facu…

16. Gould, Ernest A., and Stephen Higgs. “Impact of climate change and other factors on emerging arbovirus diseases.” Transactions of the Royal Society of Tropical Medicine and Hygiene 103.2 (2009): 109-121. http://www.idpublications.com/jo…

https://www.quora.com/What-are-the-chances-that-theres-something-else-like-Zika-coming-soon/answer/Tirumalai-Kamala

Can we assume that no dengue epidemic in the U.S. implies little chance of a Zika epidemic? (both diseases are transmitted by the same mosquito)

Tags

Aedes aegypti, Aedes albopictus, Mosquito control, Vertically transmitted infection

Not too long back Dengue epidemics were part and parcel of life in certain parts of the US (1). Florida had its last Dengue epidemic in 1934. Keeping mosquito-borne diseases at bay in the lush, warm, wet sub-tropical Florida climate is a constant tug-of-war and recent history ominously suggests that laxity in stringent, community-wide mosquito control could deliver net advantage to mosquitoes and the diseases they carry. Florida’s climate allows year-around residence of Aedes aegypti, the mosquito species that transmits Dengue and Zika in Central and South America. Thus, there’s no guarantee Dengue won’t make a comeback or that Zika can’t gain a foothold in the state. Exploring chances of Dengue and Zika in Florida helps appraise their capacity to spread into continental US and suggests that holding them at arm’s length is a fragile standoff at the best of times.

The Three Mosquiteers* In Florida’s History: Dengue, Malaria, Yellow Fever

Since at least the 1970s, Florida’s become one of the foremost global tourist destinations but a 2013 article on the history of mosquito-borne diseases in Florida (2) reminds us just how recent that transformation is. For long Florida was sparsely inhabited, its entire population numbering just 34730 in 1830 (3). As recently as the 1950s, Florida was a place to flee from in summer (4), of course only by those who could afford to do so.

Why? Simply, until recently, life in much of Florida was considered so unbearable (5), much of its population stayed concentrated in the north between Alabama and Georgia, the Florida Panhandle, a largely disease- and poverty-stricken area between Jacksonville and Pensacola, known as the ‘malaria belt’, also home to cholera, dengue, diphtheria, hookworm, influenza, pellagra, pertussis, smallpox, tetanus, typhoid, yellow fever. Though largely forgotten today, mosquito-borne diseases in the form of malaria, dengue and yellow fever thus inform a great deal of Florida’s history. Maurice Provost, the first director of what would become the Florida Medical Entomological Laboratory recalled in 1973 (see below from 6),

“My most vivid memories of malaria-control days in Florida are of the morning-after inspections of so many of the humble shacks we sprayed with DDT. The poor housewife often enough would come to me with tears of joy and show me a basketful of dead bedbugs, roaches, and other vermin, and she would exclaim that her family had spent the first night of their lives without annoyance from biting or creeping things”

Florida’s last dengue epidemic was in 1934. Reads like so much ancient history now. Why? Mosquito control (7), a stupendous achievement pretty much taken for granted not just now but already a generation back in 1981 (see below from 8, emphasis mine).

“Florida would not be where it is today were it not for mosquito control. That alone makes a lot of people mad, but they weren’t around when you could not go outside after dark and most of the coastal communities closed down during the summer. Most of the people who fight your programs are newcomers. A newcomer is now somebody who came here after 1970.”

Complacence Belied, After 1934, In 2009 Locally Acquired (autochthonous) Dengue Returned To Florida

While sporadic travel-related Dengue infections remained, Florida didn’t report any locally acquired (autochthonous) Dengue since 1934, a record broken in 2009. Starting in July 2009 and continuing until April of the following year, a total of 28 locally acquired Dengue cases were reported in Key West, FL (See figure below left from 9). Eventually a total of >90 locally acquired Dengue cases were reported in Key West alone (See figure right from 10).

Starting from tiny Key West in 2009 (see left from 11), by 2013, locally acquired Dengue had expanded upward to encompass at least 8 Florida counties (see right from 12).

Local acquisition means complete local mosquito-to-local human-to-local mosquito cycle, the step necessary for outbreaks and eventually epidemics too. Definitely the opposite of welcome news. The silver lining in this dismaying story was that Maimi-Dade County, a port with heavy traffic from Dengue-endemic countries, doesn’t appear to have conditions sufficient to sustain local Dengue transmission. Puzzling similarities in the Counties with the most number of cases, namely Key West-containing Monroe in 2009-2010 and Martin in 2013, were

• Neither is a major port of entry for either aviation or shipping.
• Both had larger numbers of locally acquired cases compared to other Florida counties.

How did Key West and Martin favor local Dengue transmission? Studies suggest factors they have in common are (12, see table below from 11)

• Tendency to keep open-air water receptacles such as bird-baths without frequently changing them.
• Keep windows open >50% of the time.
• Have >50% vegetation on their property.

OTOH, local Dengue transmission was greatly reduced if

• Empty standing water containers were changed weekly.
• Air-Conditioners (A-Cs) were used >50% of the time.
• Mosquito repellents were used routinely.

Situation in Florida is even more precarious given the fact that one study found local Florida Ae. aegypti mosquitoes capable of Vertically transmitted infection of the Dengue strain isolated from the 2009 Key West outbreak (13). When infected with Dengue virus, ~8% of these Florida mosquitoes were found capable of vertically transferring it to their eggs. Thus, Florida’s just barely keeping Dengue at arm’s length and even the slightest laxity could be all it takes for it to gain a stable foot-hold. Threat of Zika just adds to the strain on public health. Not to mention the really scary scenario if Aedes albopictus also became capable of transmitting Dengue and Zika, something it can’t at present. This would be really scary given how much more widespread this mosquito species is all across the continental US and indeed much of the temperate regions of the world.

Trouble is collective memory’s fickle and easily breeds complacence. When persistent, deeply vexing problems such as the perennial scourge of mosquitoes get intensively abated within just a generation, as happened in Florida, it doesn’t take long for collective, generation-spanning amnesia to dictate the conversation. Already back in 1991, public opinion apparently supported the idea that mosquito control officials greatly exaggerate the threat of disease to justify their jobs (4). What’s easily forgotten in such short-sighted political and economic debates is that mosquito (vector) control is inherently resource and personnel intensive and only works with sustained community support and participation (14). To quote Hribar (2, emphasis mine),

‘Is it too expensive to control Aedes aegypti? Equipment, training, pesticides, and people cost money. To do the job right, a lot of time must be devoted to seeking out larval habitats and eliminating them. Adult emergences must be dealt with promptly. The public must cooperate with public health and mosquito control agencies in the fight against Aedes aegypti. Whatever the cost surely it will be less than the hospitalization, medicines, lost wages, and funeral expenses that may be the alternative ‘

Though climate and location render Florida and other states in the Gulf Coast of the United States vulnerable to Dengue and Zika, common-sense, practical measures can do a great deal to minimize and even prevent them from getting established in the US. Apart from aggressive, community-based mosquito (vector) control, air-conditioning and using screens on doors and windows can greatly stem Ae. aegypti‘s capacity to complete Dengue and Zika‘s transmission cycle. Of course, prevention is greatly facilitated by widespread use of centralized air-conditioning and heating systems, something only to be expected in an advanced economy like the US. Given how important tourism is to Florida’s economy, one would hope the state apparatus wouldn’t hesitate to pull out all stops to prevent mosquito-borne Dengue and Zika from taking root in the state.

*: Defined here as mosquito-borne parasitic and viral diseases.

Bibliography

1. Bouri, Nidhi, et al. “Return of epidemic dengue in the United States: implications for the public health practitioner.” Public health reports 127.3 (2012): 259. http://www.ncbi.nlm.nih.gov/pmc/…

2. Hribar, L. G. “Influence and impact of mosquito-borne diseases on the history of Florida, USA.” Life Excit. Biol 1 (2013): 53-68. https://blaypublishers.files.wor…

3. Cody, Scott K. “Florida’s population center migrates through history.” Florida Focus 2.1 (2006): 1-5) http://www.bebr.ufl.edu/sites/de…

4. Mulrennan, J. A. “Benefits of mosquito control.” Mosquito control pesticides: ecological impacts and management alternatives. Conference Proceedings. Scientific Publishers, Inc. Gainesville, Florida, USA. 1991.

5. Gaiser, D. “The importance of mosquito control to tourism in Florida.” Proceedings of the Florida Anti Mosquito Association (1980).

6. Provost, Maurice W. “Environmental Quality and the Control of Biting Flies.” Symposium on Biting-Fly Control and Environmental Quality. 1973.

7. Mulrennan Jr, John Andrew. “Mosquito control-Its impact on the growth and development of Florida.” Insect Potpourri: Adventures in Entomology (1992): 75.

8. Harden, F.W. 1981. You and the environment. Journal of the Florida Anti-Mosquito Association 52:60-61. http://floridamosquito.org/Archi…

9. Trout, A., et al. “Locally Acquired Dengue-Key West, Florida, 2009-2010.” Morbidity and Mortality Weekly Report 59.19 (2010): 577-581. http://www.cdc.gov/mmwr/pdf/wk/m…

10. Rey, Jorge R. “Dengue in Florida (USA).” Insects 5.4 (2014): 991-1000. Dengue in Florida (USA)

11. Radke, Elizabeth G., et al. “Dengue outbreak in key west, Florida, USA, 2009.” Emerg Infect Dis 18.1 (2012): 135-7. http://wwwnc.cdc.gov/eid/article…

12. Teets, Frank D., et al. “Origin of the dengue virus outbreak in Martin County, Florida, USA 2013.” Virology reports 1 (2014): 2-8. https://www.researchgate.net/pro…

13. Buckner, Eva A., Barry W. Alto, and L. Philip Lounibos. “Vertical transmission of Key West dengue-1 virus by Aedes aegypti and Aedes albopictus (Diptera: Culicidae) mosquitoes from Florida.” Journal of medical entomology 50.6 (2013): 1291-1297. https://www.researchgate.net/pro…

14. Parks, Will, and Linda Lloyd. Planning social mobilization and communication for dengue fever prevention and control: a step-by-step guide. World Health Organization, 2004. https://www.researchgate.net/pro…

https://www.quora.com/Can-we-assume-that-no-dengue-epidemic-in-the-U-S-implies-little-chance-of-a-Zika-epidemic-both-diseases-are-transmitted-by-the-same-mosquito/answer/Tirumalai-Kamala

Mosquito usually carries quite infectious virus like Ebola. Do mosquitoes get infected by viruses they transmit?

Tags

Antiviral immunity, Mosquito-to-mosquito virus transmission

Thus far, ‘There is no evidence that mosquitoes or other insects can transmit Ebola virus‘ (1). However, several other viral diseases are mosquito-borne. These include Chikungunya virus, Dengue virus, Yellow fever virus, Zika virus, to mention a few. These are transmitted through the bite of infected Aedes species mosquitoes.

Mosquitoes do get infected by the viruses they transmit (See figure below from 2).

As the figure highlights, in addition to successfully replicating in the mid gut, viruses taken in during blood meals face several barriers to productive infection of mosquitoes. These include a) a time constraint in infecting mosquito mid gut epithelial cells, b) successful escape from mid gut epithelial cells after they replicate within them, and c) successful infection and replication within mosquito salivary glands.

There is also evidence of mosquito-to-mosquito virus transmission (3). While mosquito immune responses against parasitic Protozoa such as Plasmodium are quite well-studied (4), mosquitoes can also make immune responses against viruses that infect them. Studies have found specific mosquito mid-gut immune responses against Arbovirus such as Chikungunya, Dengue virus and West Nile fever (see summary figure from 5, 6).

Bibliography

1. Transmission | Ebola Hemorrhagic Fever | CDC

2. Franz, Alexander WE, et al. “Tissue barriers to arbovirus infection in mosquitoes.” Viruses 7.7 (2015): 3741-3767. Tissue Barriers to Arbovirus Infection in Mosquitoes

3. Haddow, Andrew D., et al. “First isolation of Aedes flavivirus in the Western Hemisphere and evidence of vertical transmission in the mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae).” Virology 440.2 (2013): 134-139. https://www.researchgate.net/pro…

4. Jaramillo-Gutierrez, Giovanna, et al. “Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes.” BMC microbiology 9.1 (2009): 1. https://www.researchgate.net/pro…

5. Saraiva, Raúl G., et al. “Mosquito gut antiparasitic and antiviral immunity.” Developmental & Comparative Immunology (2016).

6. Sim, Shuzhen, Natapong Jupatanakul, and George Dimopoulos. “Mosquito immunity against Arboviruses.” Viruses 6.11 (2014): 4479-4504. Mosquito Immunity against Arboviruses

https://www.quora.com/Mosquito-usually-carries-quite-infectious-virus-like-Ebola-Do-mosquitoes-get-infected-by-viruses-they-transmit/answer/Tirumalai-Kamala

What is the best repellent to avoid being bitten by a mosquito carrying the Zika virus?

Tags

DEET, Icaridin, IR3535, Permethrin, PMD

Repellents are volatile chemicals that repel insects (1, 2, 3). An ideal one would protect against a wide variety of insects for several hours at a stretch without causing any adverse reactions. However, currently available repellents are far from this ideal. Answer to which repellent is best isn’t straightforward for several reasons.

1. In the case of mosquitoes, each repellent compound has a different efficacy against different mosquito species so efficacy data against one can’t be extrapolated to another. Usually, a repellent will be able to keep any/all mosquito species at bay at first, with none managing to land and bite, but often the effect wanes differentially against different mosquito species and soon they start biting (4).
2. Formulations, which range from aerosols, creams, grease sticks, lotions, oils to sprays, greatly change the efficacy of the repellent substance (4). The formulation’s boiling point determines how much evaporates from the skin which in turn determines the concentration of volatile repellent emanating from it which in turn determines the distance mosquitoes are repelled. Two things about the repellent formulation come into play, how fast it evaporates and how deep it penetrates into the skin. Faster the former and deeper the latter, faster the repellent loses its efficacy. For e.g., formulations containing alcohol can penetrate deeper into the skin leading to faster efficacy loss.
3. Intrinsic factors influence repellent action. For e.g., sweating both attracts mosquitoes and dilutes the repellent.
4. External factors such as air temperature, humidity and wind speed also influence repellent efficacy. Warm, humid climates or high wind speed shorten the effective duration of repellent so frequent reapplications are necessary (4).

The CDC (5) lists the following as effective mosquito repellents: DEET, Icaridin (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-, 1-methylpropylester; Picaridin; KBR 3023; Bayrepel), IR3535 (Insect Repellent ethyl-butylacetyl-amino-propionate, EBAAP), oil of lemon eucalyptus (p-Menthane-3,8-diol, PMD, Citriodora). For clothing, it recommends Permethrin-treated clothing.

In the case of Zika, protection is required against not just Aedes aegypti but also A. albopictus, aka the tiger mosquito, since both mosquito species have been implicated in human Zika outbreaks. A. aegypti prefers clean indoor and outdoor water reservoirs while A. albopictus prefers natural reservoirs in gardens and forests, and usually bites outdoors. Both are day biters, preferring to bite at dawn and dusk (crepuscular periods) (6) so control is more difficult compared to night biting malaria-spreading Anopheles, where long-lasting insecticidal nets (LLIN) have proven quite effective in malaria control programs.

Most studied repellents effective at repelling A. aegypti and A. albopictus are synthetic DEET, Icaridin , IR3535 , and plant-derived PMD. Of these DEET and Icaridin have the best track record of effectiveness against Aedes.

DEET: used since the 1950s, it’s very effective against mosquitoes, ticks, biting flies, chiggers and fleas (7). Commercial repellents typically contain 20-25% DEET.

Is DEET safe, especially for pregnant women? Thus far only one randomized, double blind study tested 897 pregnant women in Thailand for regular DEET usage during their 2nd or 3rd trimester. Study showed no adverse effect on fetuses, during birth or at one year follow-up (8). However, DEET crossed the placenta since it was found in 8% of 50 randomly selected DEET users in the study. A pesticide survey among pregnant New Jersey women also found DEET crossed the placenta since again it was detected in blood and cord blood in all 150 subjects (9). However, again, with no adverse effects on new borns in terms of birth weight, head circumference or birth length. There was only a borderline association between higher DEET cord blood levels and higher abdominal circumference though its medical relevance is unclear.

DEET has some drawbacks. Effectiveness needs high concentrations of >10% and frequent re-applications. Not being very volatile means its spatial protection is short-range (10). Some evidence suggests A. aegypti can become DEET-resistant (11). Products with >25% DEET aren’t necessarily more effective against Aedes mosquitoes and they may not be as safe. Long term usage can cause skin irritation (12) and it can be absorbed through skin. If accidentally eaten, high blood concentrations are found in blood (13) with anecdotal reports of hypotension, seizures, coma or encephalopathy (14).

Icaridin: Developed by Bayer in the 1980s, unlike DEET, this synthetic repellent is odorless, non-sticky, non-greasy, doesn’t dissolve plastic, coatings or sealants, doesn’t stain clothes and is biodegradable. As effective as DEET against Aedes, also feels and smells better compared to DEET  (15). While there are few clinical trials of Icaridin, it’s reported to be safe even in children (15) and less of it gets into the blood (16) compared to DEET.

• For A. aegypti and A. albopictus, a field study in Cambodia showed a commercial 20% Icaridin spray was as effective as ethanol solution of 20% DEET over a 5 hour period, confirming results of an earlier study that compared ethanol formulations of Icaridin and DEET (17). These authors also note that adults prefer spray formulation containing 20% Icaridin, a concentration considered safe for their long-term use. OTOH, they say that 10% Icaridin lotion’s better for children since it’s adapted for their long-term use plus avoids risks associated with spraying on delicate parts of their body such as eyes, mouth, nose and skin abrasions. However, this study also found 10% Icaridin lotion was much less effective compared to 20% spray.
• A small field trial on 10 subjects in Brazil showed IR3535 as 10, 15 or 20% spray or 10 or 15% lotion, and Icaridin as 20% spray or 10% lotion were equally effective against A. aegypti for at least 6 hours (18).
• Another study (19) compared commercial formulations of DEET, PMD, citronella, geraniol, and vitamin B skin patch using cultured A. aegypti and A. albopictus.  DEET and PMD were equally effective repellents though DEET’s effect lasted longer while citronella or geraniol containing formulations and the vitamin B skin patch were ineffective.

Treated Clothing

Permethrin-treated clothing can protect against A. aegypti bites (20), usually for up to 5 to 10 washes since washing and ironing reduces the effectiveness. Interesting feature of this study was that hand- and factory-dipped clothing provided similar protection, though hand-dipped clothing is more inconsistent so requires more frequent re-application. Nevertheless, dipping clothes in permethrin could be a viable option for children’s school uniforms, for example. This concords with an older study that found permethrin-treated clothing to effectively repel A. albopictus (21). In fact, one study on permethrin-treated army uniforms found effectiveness against A. aegypti up to even 55 washings (22).

These are a mere handful of numerous studies. Bottomline, DEET = Icaridin > PMD = IR3535 would be a good rule of thumb for repellents effective against Aedes. Formulations matter. Alcohol-free ones may be effective longer. All require some level of re-application, more mosquitoes, more frequent re-applications necessary. Since mosquito-intensive areas would require more re-applications, Icaridin, being less skin-irritating compared to DEET, may be a safer choice. Lotions may be safer for children though they may not be as effective as sprays.

Bibliography

1. Dethier, V. G., Barton L. Browne, and Carroll N. Smith. “The designation of chemicals in terms of the responses they elicit from insects.” Journal of Economic Entomology 53.1 (1960): 134-136.

2. Brown, Margaret, and Adelaide A. Hebert. “Insect repellents: an overview.” Journal of the American Academy of Dermatology 36.2 (1997): 243-249.

3. Miller, J. R., et al. “Designation of chemicals in terms of the locomotor responses they elicit from insects: an update of Dethier et al.(1960).” Journal of economic entomology 102.6 (2009): 2056-2060.

4. Maibach, Howard I., Abdul A. Khan, and William Akers. “Use of insect repellents for maximum efficacy.” Archives of dermatology 109.1 (1974): 32-35.

5. http://www.cdc.gov/chikungunya/p…

6. Rozendaal, Jan A. Vector control: methods for use by individuals and communities. World Health Organization, 1997.

7. Katz, Tracy M., Jason H. Miller, and Adelaide A. Hebert. “Insect repellents: historical perspectives and new developments.” Journal of the American Academy of Dermatology 58.5 (2008): 865-871.

8. McGready, Rose, et al. “Safety of the insect repellent N, N-diethyl-M-toluamide (DEET) in pregnancy.” The American journal of tropical medicine and hygiene 65.4 (2001): 285-289. http://www.ajtmh.org/content/65/…

9. Barr, Dana Boyd, et al. “Pesticide concentrations in maternal and umbilical cord sera and their relation to birth outcomes in a population of pregnant women and newborns in New Jersey.” Science of the total environment 408.4 (2010): 790-795.

10. Bernier, Ulrich R., et al. “Comparison of contact and spatial repellency of catnip oil and N, N-diethyl-3-methylbenzamide (deet) against mosquitoes.” Journal of medical entomology 42.3 (2005): 306-311. http://digitalcommons.unl.edu/cg…

11. Stanczyk, Nina M., et al. “Behavioral insensitivity to DEET in Aedes aegypti is a genetically determined trait residing in changes in sensillum function.” Proceedings of the National Academy of Sciences 107.19 (2010): 8575-8580. http://www.pnas.org/content/107/…

12. DeGennaro, Matthew. “The mysterious multi-modal repellency of DEET.” Fly 9.1 (2015): 45-51.

13. Koren, Gideon, Doreen Matsui, and Benoit Bailey. “DEET-based insect repellents: safety implications for children and pregnant and lactating women.” Canadian Medical Association Journal 169.3 (2003): 209-212. http://www.ncbi.nlm.nih.gov/pmc/…

14. Chen-Hussey, Vanessa, Ron Behrens, and James G. Logan. “Assessment of methods used to determine the safety of the topical insect repellent N, N-diethyl-m-toluamide (DEET).” Parasit Vectors 7.1 (2014): 173. Parasites & Vectors

15. Antwi, Frank B., Leslie M. Shama, and Robert KD Peterson. “Risk assessments for the insect repellents DEET and picaridin.” Regulatory Toxicology and Pharmacology 51.1 (2008): 31-36. http://entomology.montana.edu/Pe…

16. Chen, T., et al. “Percutaneous permeation comparison of repellents picaridin and DEET in concurrent use with sunscreen oxybenzone from commercially available preparations.” Die Pharmazie-An International Journal of Pharmaceutical Sciences 65.11 (2010): 835-839. http://www.ingentaconnect.com/co…

17. Badolo, Athanase, et al. “Evaluation of the sensitivity of Aedes aegypti and Anopheles gambiae complex mosquitoes to two insect repellents: DEET and KBR 3023.” Tropical Medicine & International Health 9.3 (2004): 330-334. https://www.researchgate.net/pro…

18. Naucke, T. J., et al. “Field evaluation of the efficacy of proprietary repellent formulations with IR3535® and Picaridin against Aedes aegypti.” Parasitology research 101.1 (2007): 169-177. https://www.researchgate.net/pro…

19. Rodriguez, Stacy D., et al. “The Efficacy of Some Commercially Available Insect Repellents for Aedes aegypti (Diptera: Culicidae) and Aedes albopictus (Diptera: Culicidae).” Journal of Insect Science 15.1 (2015): 140. http://www.ncbi.nlm.nih.gov/pmc/…

20. Banks, Sarah DeRaedt, et al. “Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes aegypti: Extent and Duration of Protection.” PLoS Negl Trop Dis 9.10 (2015): e0004109. http://www.plosntds.org/article/…

21. Schreck, CARL E., and T. P. McGovern. “Repellents and other personal protection strategies against Aedes albopictus.” J Am Mosq Control Assoc 5.2 (1989): 247-250. http://www.biodiversitylibrary.o…

22. Sukumaran, D., et al. “Knockdown and repellent effect of permethrin-impregnated army uniform cloth against Aedes aegypti after different cycles of washings.” Parasitology research 113.5 (2014): 1739-1747.

https://www.quora.com/What-is-the-best-repellent-to-avoid-being-bitten-by-a-mosquito-carrying-the-Zika-virus/answer/Tirumalai-Kamala

Will climate changes have an impact on health and affect the spread of diseases such as malaria?

Tags

Chikungunya, Cholera, Climate Change, Plasmodium

Malaria morbidity and mortality (1) is typically a function of:

• Vector control as in control of malaria-infected mosquitoes.
• Ease of access to medical service, accurate and timely diagnosis, and Artemisinin-based combination therapies.
• Rural-to-Urban human population shift.
• Clean housing, ample nutrition, hygienic water management.

In other words, more resources spent, better malaria control. After all, malaria and poverty go hand in hand. Obviously w.r.t. climate change, vector control or capacity of mosquitoes to breed and spread is the weakest link in the chain.

Increased emission of greenhouse gases into the atmosphere triggers climate change. In turn, this affects temperature, rainfall and relative humidity, the same variables that influence the habitats of vectors like mosquitoes (2, 3, 4).

• More humans now live in cities, a change that in turn parallels the range of anthropophilic mosquitoes such as Aedes aegypti and Aedes albopictus (5).
• For example, each degree increase in temperature per century has increased the Northern Italy and Alps habitat of the tiger mosquito, Aedes albopictus (6).
• Tiger mosquito habitat is also expanding along the East and West coasts of the US (7).
• The tiger mosquito in particular has relevance for human diseases because of key features that make it an optimal disease-spreading agent
  • Thrives in both urban and rural human habitats.
  • Flexible breeding sites.
  • Vast geographic range that includes both US coasts, Southern Europe, South America, Africa and Southern Asia.
• During drought, again an increasing feature of climate change, we store water for longer periods, with fewer changes and cleaning, in turn leading to greater mosquito breeding and disease outbreaks (8, 9, 10).

Climate change and Malaria
Do temperature, rainfall and relative humidity affect malaria transmission? Epidemiological and lab studies suggest yes.

• When annual average relative humidity is <60%, malaria transmission is strongly inhibited (11).
• As temperatures increase, mosquitoes proliferate faster and bite more (12).
• At 19oC, immature Plasmodium vivax takes 30 days to develop fully inside the mosquito At 28oC? Only 13 days (13).

Could climate change-related environment changes impact mosquito-borne diseases? Studies suggest yes.

• One study (14) showed that coastal brackish water increases can influence mosquito-borne diseases in two ways
  • Increase local density of salt-tolerant mosquitoes like Anopheles sundaicus and Culex sitiens.
  • Make freshwater mosquitoes such as Anopheles culiefaciens, Anopheles stephensi, Aedes aegypti, Aedes albopictus salt-tolerant.

• The compelling human relevance of this study?
  • For one, >50% of the global human population lives on land <60km from the seashore (14).
  • For another, coastal area population density is projected to increase from 87 persons per sq. km in 2000 to 134 persons per sq. km in 2050 (15).
  • Human population density is likely to increase particularly in tropical areas, where mosquito-borne diseases like malaria are already endemic.
  • Thus, as a result of climate change-related changes in relative water salinity, both mosquito breeding grounds and salt-adapted mosquito species could expand. In turn, they increase likelihood of spread of mosquito-borne diseases.

• In the final analysis, climate change-related changes have the capacity to both augment and reduce spread of malaria as this table suggests (16; see figure below).

Climate change and Chikungunya
Let’s consider another mosquito-borne disease likely to spread due to climate change, Chikungunya.

• With clinical symptoms similar to Dengue fever, this novel arbovirus was first isolated in 1952 among eastern Tanzania’s Makonde people suffering from a febrile illness similar to Dengue.
• Named Chinkungunya which in the native Makonde language means ‘that which bends up‘, obviously a reference to the body contortions associated with its characteristic severe arthralgia (17, 18, 19).
  • ~2 to 6 days incubation following bite of an infected mosquito.
  • Starts with abrupt onset high fever for 1 to 7 days, crippling myalgias and lower back pain.
  • Severe arthralgias of ankles and wrists, conjunctivitis, maculopapular rash.
• Infectious bites have a nearly 100% transmission rate (20).
• Rarely fatal, complete recovery expected but with likely chronic arthritis for several months to years (21, 22).
• For decades Chikungunya was known to cause episodic outbreaks in Africa, India and southeast Asia without much notice from global health monitors until 2005 when an outbreak on the French island of Reunion spread to India affecting at least 1.4 million people (23, 24, 25).
• Many features were different about the 2005 outbreak
  • Mortality of 0.3 to 1/1000 symptomatic cases, much higher than in previous Chikungunya epidemics (26).
  • Hepatic failure, spontaneous hemorrhage, vertical mother-infant transmission (27, 28, 29).
  • Chronic, persistent arthritis with symptoms lasting even two years later (30, 31), leading to considerable disability, and public health and economic burden (32).
  • In the 2005 Reunion outbreak, Chikungunya switched vectors to the tiger mosquito, Aedes albopictus (33, 34). What are the implications of this switch?
  • Where previously, Chikungunya was primarily associated with woodland (sylvatic) mosquitoes such as Aedes africanus, A. furcifer, A. luteocephalus, A. neoafricanus, A. taylori (35, 36) that have limited habitat distribution, now it can spread faster and further, piggybacking on the vast range of the tiger mosquito (37, 38).

• Is climate change the cause of Chikungunya’s increased severity? Maybe not. What’s apparent though is that its vector switch enables it to capitalize on the climate change-induced increased spread of Aedes albopictus. As a result, Chikungunya is likely to become endemic worldwide (5, 39, 40).

Climate change and Cholera

• Vibrio cholerae, a bacterium, causes cholera. It associates with planktons and tiny crustaceans (copepods) for its survival, reproduction and transmission (41).
• As sea surface temperatures rise, phytoplanktons increase, in turn causing the increase of cholera’s reservoir, i.e.  zooplanktons such as copepods (42).
• For example, cholera outbreaks in coastal Bangladesh have been linked to plankton increases associated with local sea surface temperature increase (43).

Bibliography

1. Gubler, Duane J., et al. “Climate variability and change in the United States: potential impacts on vector-and rodent-borne diseases.” Environmental health perspectives 109.Suppl 2 (2001): 223. Page on nih.gov)
2. Bai, Li, Lindsay Carol Morton, and Qiyong Liu. “Climate change and mosquito-borne diseases in China: a review.” Global Health 9.10 (2013): 1-22.Page on biomedcentral.com
3. Lee, Su Hyun, et al. “The effects of climate change and globalization on mosquito vectors: evidence from Jeju Island, South Korea on the potential for Asian Tiger Mosquito (Aedes albopictus) influxes and survival from Vietnam rather than Japan.” PloS one 8.7 (2013): e68512. Page on plosone.org
4. Eisen, Lars, and Chester G. Moore. “Aedes (Stegomyia) aegypti in the continental United States: a vector at the cool margin of its geographic range.” Journal of medical entomology 50.3 (2013): 467-478.
5. Le Anh, P. Nguyen, et al. “Abundance and prevalence of Aedes aegypti immatures and relationships with household water storage in rural areas in southern Viet Nam.” International health 3.2 (2011): 115-125.
6. Roiz, David, et al. “Climatic factors driving invasion of the tiger mosquito (Aedes albopictus) into new areas of Trentino, northern Italy.” PLoS One 6.4 (2011): e14800. Page on plosone.org
7. Rochlin, Ilia, et al. “Climate change and range expansion of the Asian tiger mosquito (Aedes albopictus) in Northeastern USA: implications for public health practitioners.” PloS one 8.4 (2013): e60874. Page on plosone.org
8. Subra, R. “The regulation of preimaginal populations of Aedes aegypti L.(Diptera: Culicidae) on the Kenya coast. I. Preimaginal population dynamics and the role of human behaviour.” Annals of tropical medicine and parasitology 77.2 (1983): 195-201.
9. Chretien, Jean-Paul, et al. “Drought-associated chikungunya emergence along coastal East Africa.” The American journal of tropical medicine and hygiene 76.3 (2007): 405-407. Page on usda.gov
10. Islam, Mohammad Nazrul, et al. “Prevalence of Malaria, Dengue, and Chikungunya Significantly Associated with Mosquito Breeding Sites.” The Journal of IMA 43.2 (2011): 58. Page on researchgate.net
11. Yang, Guo-Jing, et al. “Mapping and predicting malaria transmission in the People’s Republic of China, using integrated biology-driven and statistical models.” Geospatial health 5.1 (2010): 11-22. Page on geospatialhealth.net
12. Epstein, Paul R. “Is global warming harmful to health?.” Scientific American 283.2 (2000): 50-57. Page on vcharkarn.com
13. Liu, F. M., et al. “Effect of temperature on the development of Anopheles sinensis and the disease transmitted.” Chin J Vector Biol Cont 9 (1998): 185-187.
14. Ramasamy, Ranjan, and Sinnathamby Noble Surendran. “Global climate change and its potential impact on disease transmission by salinity-tolerant mosquito vectors in coastal zones.” Frontiers in physiology 3 (2012). Page on nih.gov
15. Page on unep.org
16. Stanaway, Jeffrey D., and Jonathan D. Mayer. “Climate Variability and Change and Its Effects on Malaria.” Geography Research Forum. Vol. 31. 2011. Page on bgu.ac.il
17. Robinson, Marion C. “An epidemic of virus disease in Southern Province, Tanganyika territory, in 1952–1953.” Transactions of the Royal Society of Tropical Medicine and Hygiene 49.1 (1955): 28-32. Page on suz.free.fr
18. Mason, P. J., and A. J. Haddow. “An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–1953: An additional note on Chikungunya virus isolations and serum antibodies.” Transactions of the Royal Society of Tropical Medicine and Hygiene 51.3 (1957): 238-240.
19. Lumsden, W. H. R. “An epidemic of virus disease in Southern Province, Tanganyika territory, in 1952–1953 II. General description and epidemiology.” Transactions of the Royal Society of Tropical Medicine and Hygiene 49.1 (1955): 33-57.
20. Burt, Felicity J., et al. “Chikungunya: a re-emerging virus.” The Lancet 379.9816 (2012): 662-671. Page on hospitalameijeiras.sld.cu
21. Robinson, Marion C. “An epidemic of virus disease in Southern Province, Tanganyika territory, in 1952–1953.” Transactions of the Royal Society of Tropical Medicine and Hygiene 49.1 (1955): 28-32. Page on suz.free.fr
22. Rodrigues, F. M., et al. “Etiology of the 1965 epidemic of febrile illness in Nagpur city, Maharashtra State, India.” Bulletin of the World Health Organization 46.2 (1972): 173. Page on whqlibdoc.who.int
23. Chikungunya and Dengue in the south west Indian Ocean
24. Renault, Philippe, et al. “A major epidemic of chikungunya virus infection on Reunion Island, France, 2005–2006.” The American journal of tropical medicine and hygiene 77.4 (2007): 727-731. A Major Epidemic of Chikungunya Virus Infection on Réunion Island, France, 2005-2006
25. Pialoux, Gilles, et al. “Chikungunya, an epidemic arbovirosis.” The Lancet infectious diseases 7.5 (2007): 319-327. Page on hospitalameijeiras.sld.cu
26. Burt, Felicity J., et al. “Chikungunya: a re-emerging virus.” The Lancet 379.9816 (2012): 662-671. Page on hospitalameijeiras.sld.cu
27. Gérardin, Patrick, et al. “Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Reunion.” PLoS Med 5.3 (2008): e60. Page on plosmedicine.org
28. Economopoulou, A., et al. “Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Reunion.” Epidemiology and infection 137.04 (2009): 534-541. Page on edoc.rki.de
29. Borgherini, Gianandrea, et al. “Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients.” Clinical Infectious Diseases 44.11 (2007): 1401-1407. Early Clinical and Laboratory Features in 157 Adult Patients
30. Enserink, Martin. “Massive outbreak draws fresh attention to little-known virus.” Science 311.5764 (2006): 1085-1085.
31. Queyriaux, Benjamin, et al. “Clinical burden of chikungunya virus infection.” The Lancet infectious diseases 8.1 (2008): 2-3)
32. Gérardin, Patrick, et al. “Perceived morbidity and community burden after a Chikungunya outbreak: the TELECHIK survey, a population-based cohort study.” BMC medicine 9.1 (2011): 5. Page on biomedcentral.com
33. Schuffenecker, Isabelle, et al. “Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak.” PLoS Med 3.7 (2006): e263. Page on plosmedicine.org
34. Charrel, Rémi N., Xavier de Lamballerie, and Didier Raoult. “Chikungunya outbreaks-the globalization of vectorborne diseases.” New England Journal of Medicine 356.8 (2007): 769. Page on researchgate.net
35. Jupp, P. G., and B. M. McIntosh. “Aedes furcifer and other mosquitoes as vectors of chikungunya virus at Mica, northeastern Transvaal, South Africa.” J Am Mosq Control Assoc 6.3 (1990): 415-420. Page on biodiversitylibrary.org
36. Diallo, Mawlouth, et al. “Vectors of Chikungunya virus in Senegal: current data and transmission cycles.” The American journal of tropical medicine and hygiene 60.2 (1999): 281-286. Page on ajtmh.org
37. Rezza, G., et al. “Infection with chikungunya virus in Italy: an outbreak in a temperate region.” The Lancet 370.9602 (2007): 1840-1846.
38. Pagès, Frédéric, et al. “Aedes albopictus mosquito: the main vector of the 2007 Chikungunya outbreak in Gabon.” PLoS One 4.3 (2009): e4691. Page on plosone.org
39. Dhiman, Ramesh C., et al. “Climate change and threat of vector-borne diseases in India: are we prepared?.” Parasitology Research 106.4 (2010): 763-773;
40. Ditsuwan, Thanittha, et al. “Assessing the spreading patterns of dengue infection and chikungunya fever outbreaks in lower southern Thailand using a geographic information system.” Annals of epidemiology 21.4 (2011): 253-261. Page on researchgate.net
41. Lipp, Erin K., Anwar Huq, and Rita R. Colwell. “Effects of global climate on infectious disease: the cholera model.” Clinical microbiology reviews 15.4 (2002): 757-770. Page on paho.org
42. Rita, R. “Cholera and climate: a demonstrated relationship.” Transactions of the American Clinical and Climatological Association 120 (2009): 119. Page on nih.gov
43. Kanungo, S., et al. “Cholera in India: an analysis of reports, 1997-2006.” Bulletin of the World Health Organization 88.3 (2010): 185-191. Page on www.who.int

https://www.quora.com/Will-climate-changes-have-an-impact-on-health-and-affect-the-spread-of-diseases-such-as-malaria/answer/Tirumalai-Kamala