Brazil’s Yellow Fever outbreak: Medical stuff we should know, from NAIAD

March 9, 2017

Accurate information can be the greatest tool in the fight against diseases, infectious or vector-borne. NAIAD slide.

Accurate information can be the greatest tool in the fight against diseases, infectious or vector-borne. NAIAD slide.

Brazil endures an outbreak of Yellow Fever in early 2017. Mosquitoes transmit Yellow Fever from one mammal host to another. Famously, Yellow Fever had to be controlled to allow construction of the Panama Canal between 1910 and 1915.

It should be just a matter of days, or perhaps a few hours, before harpies on the right and in anti-science trenches demand “return” of DDT to fight this outbreak, arguing that EPA didn’t know what it was doing when it banned DDT from farm use, and probably dropping cheap shots at Rachel Carson and “environmentalists.”

Yellow Fever is usually carried by mosquitoes in the species Aedes aegypti, a nasty little bug that carries several diseases to humans including Zika virus and West Nile virus.

Distribution of Aedes aegypti mosquitoes in the U.S. Map by U.S. CDC, via Wikipedia

Distribution of Aedes aegypti mosquitoes in the U.S. Map by U.S. CDC, via Wikipedia

Astute observers know that A. aegypti are almost ubiquitous in warmer human cities, so the transmission of the disease requires only that a host (usually human) shows up infected with the pathogen, and an epidemic might occur.

Those observers also know that all mosquitoes are resistant or immune to DDT and frequently to other pesticides as well, their having been bombarded with pesticides for 60 or more years, and consequently having evolved resistance alleles. So spraying with DDT won’t work.

That’ won’t stop those who relish slandering Carson or who wish to impugn the humanity and good motives of environmentalists.

Get facts, first.

Come Dr. Anthony Fauci and Dr. Cahtharine Paules of the U.S.’s National Institute of Allergy and Infectious Diseases (NAIAD), part of the National Institutes of Health (NIH) to offer information to calm the hyperventilated, and to inform the serious and concerned citizen with an article in the New England Journal of Medicine, explaining Brazil’s problem, Yellow Fever, and what U.S. residents need to do, and this press release from NAIAD to get the key points across quickly.

Will anyone listen?

Yellow Fever in the Americas

Current Outbreak Merits Close Watch
March 8, 2017

The unusually large outbreak of yellow fever now occurring in rural Brazil deserves careful attention by world health authorities, notes Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health. Writing in a Perspectives piece for the New England Journal of Medicine, Dr. Fauci and his associate Catharine I. Paules, M.D., note that this latest outbreak of a serious mosquito-borne virus comes as Zika virus, which is spread by the same mosquito as yellow fever virus, continues to affect countries throughout the Americas.

Historically, yellow fever has claimed millions of lives, including many thousands in the United States. The Philadelphia epidemic of 1793, for example, killed approximately ten percent of the city’s population. In its most serious form, yellow fever symptoms include high fever, hemorrhagic manifestations, kidney failure, liver malfunction and jaundice (yellowish appearance of the eyes and skin, which gives the disease its name.)

A vaccine has been available since 1937 and confers lifelong immunity in up to 99 percent of those who receive it. Extensive immunization campaigns, along with effective mosquito control—especially in developed countries—have reduced yellow fever cases worldwide. Nevertheless, localized outbreaks in parts of Africa and Central and South America account for an estimated 84,000 to 170,000 severe cases of disease and between 29,000 and 60,000 deaths annually.

The Brazilian outbreak is a manifestation of the “sylvatic,” or jungle, transmission cycle in which forest-dwelling mosquitoes spread the virus primarily to non-human primates, with humans serving only as incidental hosts. At this time, there is no evidence that the outbreak is transforming into its “urban” cycle, but authorities should remain alert for this possibility, the authors note. In the urban cycle, yellow fever virus is usually spread by city-dwelling Aedes aegypti mosquitoes directly to people. An urban cycle of yellow fever in Angola and the Democratic Republic of Congo that began in late 2015 caused 961 confirmed cases and 137 deaths. During that outbreak, write Drs. Fauci and Paules, the world’s emergency vaccine stockpile reserve was exhausted, limiting the number of available vaccine doses and making the outbreak more difficult to control. To prevent a similar occurrence during a future yellow fever outbreak in Brazil or elsewhere, “early identification of cases and rapid implementation of public health management and prevention strategies, such as mosquito control and appropriate vaccination, are critical,” they write.

In an era of frequent international travel, an increase in domestic cases in Brazil has the potential to spread yellow fever to non-endemic areas and could pose serious disease-control challenges, Drs. Fauci and Paules observe. They urge clinicians, especially those in the United States and other places where yellow fever is uncommon, to inform themselves about yellow fever symptoms and to adopt a high index of suspicion for this diagnosis, particularly when examining travelers returning from affected regions.

ARTICLE:
CI Paules and AS Fauci. Yellow fever: Once again on the radar screen in the Americas. New England Journal of Medicine DOI: 10.1056/NEJMp1702172 (2017).

WHO:
Dr. Fauci is available to discuss this article.

CONTACT:
To schedule interviews, please contact Anne A. Oplinger, (301) 402-1663, aoplinger@niaid.nih.gov.

Map of Brazil showing confirmed cases of Yellow Fever

Map of Brazil showing confirmed cases of Yellow Fever “in the current outbreak,” as of March 2017. Information from Brazil’s Ministry of Health. NEJM image.

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2001 press release from NIAID, mosquito genome sequencing project: “DDT was once a powerful tool”

March 24, 2014

Caption from Vanderbilt University: Figure 1. Anopheles freeborni mosquito taking a blood meal. Image reproduced from the Centers for Disease Control http://www.cdc.gov/malaria/about/biology/mosquitoes/, CDC, public domain.

Caption from Vanderbilt University: Figure 1. Anopheles freeborni mosquito taking a blood meal. Image reproduced from the Centers for Disease Control http://www.cdc.gov/malaria/about/biology/mosquitoes/, CDC, public domain.

Press release from the NIH National Institute of Allergy and Infectious Diseases (NIAID):

Anopheles gambiae Genome Sequencing Project

March 5, 2001

 


Statement of Anthony S. Fauci, M.D.
Director, National Institute of Allergy and Infectious Diseases


Today, a global network of researchers announced that they are collaborating in sequencing the genome of Anopheles gambiae, the mosquito responsible for most cases of malaria in Africa. The National Institute of Allergy and Infectious Diseases (NIAID) applauds the efforts of the network and their goal of obtaining sequence data by the end of the year.

This information, together with the knowledge gained from the sequences of malaria parasites and the human genome, will provide researchers with a wealth of genomic data necessary for understanding this complex disease. (See the communiqueExternal Web Site Policy.)

The need for a multifaceted commitment to fight malaria and develop new and improved treatments, diagnostics and vaccines has never been greater. According to the World Health Organization, an estimated 300 to 500 million cases of malaria occur annually; in 1999, an estimated 1.1 million deaths were attributed to malaria, most of which occurred in children under the age of 5. Malaria is a public health threat in more than 90 countries, where 40 percent of the world’s population lives. Because of the enormity of this problem, NIAID has made malaria research a central focus of our scientific portfolio and supports a comprehensive research program, which includes basic, field-based and clinical research.

Malaria is caused by a single-celled parasite that is spread to humans by mosquitoes. The control of malaria continues to be a challenge because of the dual problems of increased rates of insecticide resistance in mosquitoes and increased rates of drug resistance in the malaria parasites. Reducing disease transmission by mosquito control has been a mainstay of regional and global malaria control programs. The insecticide DDT was once a powerful tool in global efforts to eradicate malaria. With the development of DDT-resistant mosquitoes, new tools are needed to control this disease. An improved understanding of the basic biology of mosquitoes and their genomes will contribute to our ability to understand and monitor insecticide resistance, develop new insecticides, and ultimately help control the malaria pandemic.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health ®

Some points to ponder, 13 years later:

  1. Dr. Fauci notes that DDT was, at one time, a powerful tool to fight malaria — but no longer.  DDT resistant mosquitoes means new tools must be found to replace DDT.
  2. Fauci makes no mention of a shortage of DDT for any reason.  It appears from the press release that DDT’s widespread use is compromised only by its decreasing effectiveness, not by any ban from any governmental entity.
  3. In 1999, 15 years ago now, about 1.1 million people died from malaria annually; estimates cited here are that 300 million to 500 million people actually got a bout of malaria through the year.  This compares with 2012 figures of fewer than 700,000 dead, and fewer than 250 million infections.
  4. Fauci said that, if malaria is to be defeated, it must be attacked on multiple fronts.  Spraying insects alone is not enough, increasing medical care alone is not enough — no single action provides a panacea.

 


NIH notes progress against malaria on World Malaria Day 2012

April 28, 2012

Press release from the National Institutes of Health, for World Malaria Day (April 25, 2012):

For Immediate Release
Tuesday, April 24, 2012

NIH statement on World Malaria Day – April 25, 2012

B. F. (Lee) Hall, M.D., Ph.D., and Anthony S. Fauci, M.D.
National Institute of Allergy and Infectious Diseases

On World Malaria Day, we stand at a critical juncture in our efforts to control a global scourge. This year’s theme “Sustain Gains, Save Lives: Invest in Malaria” stresses the crucial role of continued investment of resources to maintain hard-won gains. Lives have indeed been saved. According to World Health Organization (WHO) estimates, annual deaths from malaria decreased from roughly 985,000 in 2000 to approximately 655,000 in 2010. Improvements were noted in all regions that WHO monitors, and, since 2007, four formerly malaria-endemic countries — the United Arab Emirates, Morocco, Turkmenistan and Armenia — have been declared malaria-free. However, about half of the world’s population is at risk of contracting malaria, and the disease continues to exact an unacceptably high toll, especially among very young children and pregnant women.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is committed to maintaining the research momentum needed to eradicate this mosquito-borne parasitic disease. Our investments include programs designed to strengthen research capacity in those countries most affected by malaria. For example, through the 2010 International Centers of Excellence for Malaria Research initiative, NIAID has established 10 research centers in malaria-endemic regions around the world. NIAID also provides access for U.S. and international scientists to multiple research resources as well as training for new investigators. Additionally, NIAID supports the Global Malaria Action Plan (GMAP), an international framework for coordinated action designed to control, eliminate and eradicate malaria.

NIAID’s research portfolio includes an array of projects aimed at better understanding the disease process and finding new and improved ways to diagnose and treat people with malaria, control the mosquitoes that spread it, and prevent malaria altogether through vaccination.

Earlier this month, an international team including NIAID-funded investigators reported that resistance to artemisinin — a frontline malaria drug — has spread from Cambodia to the border of Thailand and Burma, underscoring the importance of continued efforts to detect artemisinin resistance and slow its spread. Other grantees have identified a major region of the malaria parasite genome associated with artemisinin resistance, raising the possibility that scientists will have a new way to monitor the spread of drug resistance in the field.

The spread of artemisinin-resistant malaria highlights the need for new and improved malaria drugs. Two recently completed drug screening projects offer some hope. In one project, NIH scientists screened nearly 3,000 chemicals, and found 32 that were highly effective at killing numerous genetically diverse malaria parasite strains. Another screening project identified a new class of compounds that inhibits parasites in both the blood stage and in the liver. The research could lead to the development of malaria drugs that attack the parasite at multiple stages in its lifecycle, which would hamper the parasite’s ability to develop drug resistance.

Work continues on a novel anti-malaria compound, NITD609, first described by NIAID-supported researchers in 2010. A mid-stage clinical trial to assess NITD609’s activity in people began in Thailand this year. Research on NITD609 is a continuing collaboration among NIH-funded scientists, the pharmaceutical company Novartis, and the nonprofit Medicines for Malaria Venture.

Because the risk of childhood malaria is related to exposure before birth to the malaria parasite through infected mothers, NIAID scientists recently initiated a program on malaria disease development in pregnant women and young children that could yield new preventive measures and treatments for these most vulnerable groups.

The mosquitoes that spread malaria are also the target of NIAID-supported science. In 2011, researchers identified bacteria that render mosquitoes resistant to malaria parasites. Further study is needed, but it may one day be possible to break the cycle of infection by reducing the mosquito’s ability to transmit malaria parasites to people.

A vaccine to prevent malaria has been frustratingly elusive, and so initial positive results reported last year by the PATH Malaria Vaccine Initiative, GlaxoSmithKline Biologicals and their collaborators came as welcome news. In a late-stage clinical trial in approximately 6,000 African children, the candidate vaccine, known as RTS,S, reduced malaria infections by roughly half. Currently, eight other vaccine candidates are being tested in NIAID-supported clinical trials. One of them uses live, weakened malaria parasites delivered intravenously to prompt an immune response against malaria. An early-stage clinical trial of this vaccine candidate began at NIH earlier this year.

Whether the remarkable returns on investment in malaria control will continue in years ahead depends on our willingness to commit needed financial and intellectual resources to the daunting challenges that remain. On World Malaria Day, we join with our global partners in affirming that commitment and rededicating ourselves to the efforts to defeat malaria worldwide.

For more information on malaria, visit NIAID’s malaria Web portal.

Lee Hall, M.D., Ph.D., is Chief of the Parasitology and International Programs Branch in the NIAID Division of Microbiology and Infectious Diseases. Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health


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