Malaria Outbreak in Palm Beach, Florida

Americans living within the borders of the United States feel removed from the problem of malaria. Every so often it's mentioned in passing: Ashton Kutcher buys mosquito nets for children in Africa. The Gates Foundation makes a donation. But, this deadly parasite can infiltrate loosely-screened borders of any country. Malaria only needs to hijack the immune system of a single individual in order to start an epidemic.

In 2003, Palm Beach saw an outbreak of malaria. Victims ranged in wealth and status, profession and hobbies. All but one contracted malaria without having set foot outside the United States. "The hospital staff, inexperienced in working with the disease, failed to correctly identify the infections" (Packard 6). Health-care providers did not "consider malaria as a possible cause of fever among patients who have not traveled," but who experience "alternating fevers, rigors, and sweats with no obvious cause" (CDC). Calling it pneumonia and prescribing antibiotics, the hospitals sent the patients home, where they continued "to infect local mosquitoes" (Packard 6).

Anopheles mosquitoes (the ones that transmit malaria) swarm within the United States. "Palm Beach County was riddled with drainage ditches and canals, which were prime habitats for" mosquitoes (Packard 6). Between 1992 and 2003, "11 outbreaks" including at least twenty cases of "locally acquired mosquito-transmitted malaria" were reported to the CDC (CDC).

It only takes one infected individual to start an outbreak. Patient zero [the first case] may not show outward signs of the disease. This carrier could be on a regiment of symptom-suppressing medications, be recently infected, or even be immune to malaria.

In the particular case of the Palm Beach outbreak, the CDC "concluded that a migrant worker or international traveler might have been involved" (Packard 6). That traveler was not identified. The Palm Beach outbreak "demonstrated the potential for reintroduction of malaria into the United States despite intense surveillance, vector-control activities [vector=agent], and local public efforts to educate clinicians and the community" (Packard 6). It is impossible to prevent malaria from penetrating the US borders when so much of the world suffers heavily from this disease.

Malaria is a global disease. It will only be controlled by a united global assault dedicated to eradication.

Sources:
CDC. "Local transmission...". MMWR Weekly. 26 Sept 2003.

Packard, Randall M. The Making of a Tropical Disease: A short history of malaria. John Hopkins: 2007.

Malaria in Tibet

Rarely a soul considers the risk of malaria while gazing upon the snow-covered Himalayas. Why should one bother? Tibet's high-altitude and cold-weather eliminate malaria-transmitting mosquitoes in most regions. For this reason, many travel books and web sites declare that "there is no risk of malaria in Tibet" (NaTHNaC). Unfortunately, this is absolutely untrue.



"Malaria is endemic in Linzhi Prefecture in the Tibet Autonomous Region (TAR), but the vector [definition: agent] for malaria transmission" was not identified until recently. It is now believed that the mosquito, "Anopheles pseudowillmori[,] is the predominant malaria vector" in the region (Song). Preventative treatment "is recommended...for travel along the valley of the Zangbo river in the extreme southeast" of Tibet (MD). "Anti-malaria medication is recommended for low-lying subtropical areas", particularly "during the rainy season" (Dorje 49).

Tibet is home to the "Falciparum type of malaria," which is considered to be the most dangerous and most deadly strain of malaria. "Various combinations of drugs are being used such as Quinine, Tetracycline or Halofantrine. If falciparum type of malaria is definitely diagnosed, it is wise to get a good hospital as treatment can be complex and the illness very serious" (Dorje 58). Clearly, "protection against mosquitoes and drug prophylaxis against malaria are essential" when traveling to certain areas of Tibet, and all travelers should be aware of the risk of infection (51).

Sources:

Dorje, Gyurme. Tibet handbook: with Bhutan.

Galuzzi, Luca. Photo.

MD Travel Health. "Tibet". 28 August 2009.

NaTHNaC. "China (Tibet)." 28 August 2009.

Song, Wu. Et al. Malaria Journal 2009. "Anopheles pseudowillmori is the predominant malaria vector in Motuo County, Tibet Autonomous Region." 16 March 2009.

Genetically-engineered malaria vaccine

Scientists have created a "weakened strain of the malaria parasite" that "will be used as a live vaccine against the disease." This type of vaccine "has proven successful in eradicating smallpox and controlling diseases such as flu and polio" (Walter). It has already been advantageous in animal studies, and it is hoped that it will prove successful when it enters human trials (slated for early next year).

Professor Alan Cowman, head of the Walter and Eliza Hall Institute's Infection and Immunity division, said that "in developing the vaccine the research team...deleted two key genes in the Plasmodium falciparum parasite - which causes the form of malaria most deadly to humans" (Walter). "The deletions did not affect the parasites throughout most of the life cycle," but "by removing the genes the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death" (Cowman; Walter). The photo to the left shows the parasitic cells during the liver stage (WT is normal).

The fact that the deletion of the genes "did not result in any observable defect during blood-stage replication...indicated that gene deletions did not affect the sexual stages of the parasite" (Cowman). "Although two genes have been deleted the parasite is still alive and able to stimulate the body's protective immune system to recognize and destroy incoming mosquito-transmitted deadly parasites" (Walter).

"Similar vaccines" have "been tested in mice and offered 100 per cent protection against malaria infection." Cowman "said it was hoped the vaccine would produce similar results in humans" (Walter). Whenever working with an attenuated [definition: weakened] strain of a disease, mutation is always a concern. Some people fear that the parasite will mutate to a viable form, thereby infecting individuals through the vaccine. "Professor Cowman said it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite" (Walter).

The fact that two essential genes have been deleted "make it extremely unlikely that the attenuated parasite vaccine could restore its capacity to multiply and lead to disease." The scientists believe that their "genetically attenuated parasite approach provides a safe and reproducible way of developing a whole organism malaria vaccine," which has the unique ability of being nearly 100% effective (Walter).


Sources:
Cowman, Alan F. et al. "Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design." 10 June 2009.

Walter and Eliza Hall Institute (2009, August 24). First Genetically-engineered Malaria Vaccine To Enter Human Trials. ScienceDaily.

The solution with a crystalline heart

A team at McGill University (and RI-MUHC) in Montreal is scrambling to create a malaria vaccine. The researchers, lead by Dr. Martin Oliver, "may have blazed a trail towards the development of vaccine-like treatments to limit the severity of the devastating parasitic ailment" (Science).



The team's new discovery may lead to the development of a medication that stops malaria from creating the debilitating inflammation that is associated with malaria. "Inside the human body, the malaria parasite infects red blood cells where it survives and reproduces by feeding on the cells' contents. Eventually the cells burst, releasing the parasites and also a waste byproduct of their reproductive process: hemozoin" (Tiemi). Hemozoin is the "chemically inert crystalline substance produced in the digestive food vacuole of blood-stage malaria parasites" (Parasitology).

Although chemically inert, it is still a foreign substance in the body. The Hemozoin is "one way by which the immune system is alerted to malarial infection." It "activates the immune system, resulting in the production of inflammation mediators and in the high fever." The researchers believe that hemozoin "may be the missing link that explains why malaria leads to devastating inflammation and fever...The researchers believe it will be possible to familiarize the immune system to small quantities of hemozoin and diminish the inflammatory response in the event of infection, according to a principle similar to that of vaccines" (Science). Dr. Olivier explains that "Now our picture of the process that goes from infection to fever is more or less complete."

However, a final solution is not yet apparent. "Malaria is too complex to be narrowed down to one single mechanism" (Tiemi). Although the relationship between hemozoin and inflammation is important, there are most like many other mechanisms at work.

Will a malaria vaccine ever be available? It is certainly possible, but more research and development is needed before we will know for sure.

Sources:

Parasitology Encyclopedia. Hemozoin.

Tiemi Shio M, Eisenbarth SC, Savaria M, Vinet AF, Bellemare M-J, et al. Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases. PLoS Pathogens, 2009; 5 (8): e1000559 DOI: 10.1371/journal.ppat.1000559

Hempelmann, Birefringent Plasmodium falciparum hemozoin. [Photo]

Science Daily. "Towards Malaria 'Vaccine': Discovery Opens The Door To Malaria-prevention Therapies." 23 Aug 2009.

World Mosquito Day

The 20th of August is World Mosquito Day. What are you doing to stop malaria?

World Mosquito Day was introduced in "an effort to remind the public about the continuing threat of malaria and other diseases transmitted by mosquitoes" (Mirsky). "Each year, approximately 350 to 500 million people are infected with malaria, killing 1 to 3 million people, mostly young children in Sub-Saharan Africa. Only female Anopheles mosquitoes that had previously bitten a person infected malaria will transmit the disease. Currently there is no vaccine that can provide high level of protection, and malaria parasites have evolved to resist many antimalarial drugs" (NowPublic).

Unfortunately, "it's not a day to celebrate" instead, it's "an awareness day. Ronald Ross of the Liverpool School of Tropical Medicine originated World Mosquito Day in 1897. He's the guy who figured out that mosquitoes carried the malaria parasite. He got one of the first Nobel Prizes for it in 1902" (Mirsky). By the way, he was also knighted in 1911. "Sir Ronald Ross was a British physician born in Almora, India. He had the breakthrough discovery during the dissection of a specific species of mosquito, the Anopheles, previously fed on a malaria patient. Malaria parasite was found on the mosquito and on its salivary glands" (NowPublic).

"112 years later, the fight against malaria is still on" (NowPublic). On this World Mosquito Day, motivate yourself to mention malaria and it's global threat to your peers, acquaintances, or that woman who swats at mosquito while she's waiting for the bus. Together, we can Bite Malaria Back.

Sources:
Mirsky, Steve. "Bite Back on World Mosquito Day." Scientific American. 19 August 2009.
NowPublic. "World Mosquito Day on August 20: Fight against Malaria" 19 August 2009.
Photograph by Hugh Sturrock

Ethiopia's epic battle against the Waba and malaria

Wäba: a mosquito that is carrying malaria (Amharic).

Does it strike you as strange that a language would have a specific term for a malaria-carrying mosquito? In a country that has seen 9 million cases of malaria per year, a distinction between malaria-infested mosquitoes and unaffected mosquitoes is necessary (UNICEF). Ethiopia is hit hard by malaria, but with tremendous dedication, the country is making advances against the disease.

"Historically, a malaria epidemic hits Ethiopia every five to eight years. The last one, in 2003-and four, caught the country unaware. Millions contracted the disease. Nobody knows how many died." Now, "Ethiopia is gearing up for an epic battle with malaria, possibly later this year. The stakes are high, with international aid agencies betting millions of dollars that the Horn of Africa's largest country can wipe out a disease that kills at least a million Africans every year" (Heinlein).

"Malaria is seasonal in Ethiopia coming after the beginning of the rainy season. September and October are usually the months that see the highest number of cases. Will there be more than usual this year? The head of USAID's malaria programme in Ethiopia, Richard Reithinger, says only time will tell, but if it is an epidemic year then some 10 million cases could be expected" (Chinnock). "Aid agencies have spent hundreds of millions of dollars trying to prevent the next outbreak" and "30,000 health extension workers" have been deployed to combat malaria by eradicating mosquitoes and educating the public (Heinlein). "Hospitals are also being put on alert and, meanwhile, the country continues with its ambitious programme to distribute 20 million insecticide-treated bednets" (Chinnock). "In a country with a doctor shortage and a mostly rural population...bednets for all, and an army of village-level health workers are the cornerstones of the strategy to beat the disease" (Heinlein).

The strategy of maintaining village health personnel and distributing anti-mosquito bednets is working for Ethiopia. "In 2005, the Ethiopian government unveiled an ambitious strategy, with donor support, to deliver two mosquito nets to every family at risk. By January 2008, 20.5 million bed nets had been delivered and a third of at-risk children were sleeping in safety... Within three years of the start of the program, cases of malaria, and death rates, had been halved" (Coghlan). With continued support, Ethiopia might just be able to make malaria a disease of the past.

Sources:
Chinnock, Paul. "Ethiopia will expand malaria control efforts." TropIKA.net. 23 Mar 2009.
Coghlan, Nora. "SMART Aid helps Ethiopia halve malaria deaths in two years." ONE International. 12 June 2009.
Heinlein, Peter. Addis Ababa. "Ethiopia Prepares for Battle with Malaria." VOA News. 20 March 2009.
UNICEF Ethiopia. http://www.unicef.org/ethiopia/malaria.html

Malaria in Nigeria

Fatima (age of 31) has "seen five children into the world." Two of her babies have "died of malaria. When a member of her family falls ill, it is to home remedies and prayer to which Fatima turns. Living in a village in northern Nigeria that is 25 kilometres from the nearest town and without a health clinic or registered drug store, she has little choice" (DFID). [Photo from the DFID]

"Malaria is endemic in Nigeria with about 97% of the population at risk of infection" (Roll). "In Nigeria, malaria causes the deaths of an estimated 250,000 children under the age of five" and a total of 300,000 children every year (UNICEF). In 2007, there were nearly 5.5 million reported cases of malaria in Nigeria (Roll). "Malaria occurs in all parts of Nigeria, including large cities. Transmission is very intense, thus the risk of getting bitten by a malaria-carrying mosquito is very high" (CDC).

"Nigeria, with a population of 148 million, contributes a quarter of the malaria burden in Africa - 50% of the population will have at least one malaria attack each year" (DFID). Many will go unreported and untreated by medical professionals. Clinics are overloaded with the sick and many individuals cannot reach or afford medical help. Still, "malaria is responsible for about 66 per cent of all clinic visits in Nigeria. Health workers are sometimes forced to work overtime, and doctors and nurses can be on duty for over 12 hours a day. Still, women and children have to wait for hours before receiving medical consultation" (UNICEF).

"There is a lot of activity and momentum to combat malaria in Nigeria, but deadly gaps still exist. More needs to be done to prevent children from being infected and ensure access to quality malaria treatment," says Suomi Sakai (UNICEF Representative in Nigeria). Education of the local population "is an important part of UNICEF's malaria prevention work." Doctors and medical personnel must learn "how to prevent, recognize and treat malaria" (UNICEF). Furthermore, everyone needs to know how to properly protect themselves and their families from the mosquitoes that carry the deadly disease.

"However, even when people have been educated about malaria, poverty often stops them from seeking treatment. "Most can't afford the ITNs [Insecticide Treated Nets] or the ACT [Artemisinin-based combination therapy], which cures malaria," says Maryam Hashim (Wandi Primary Health Clinic).

Some level of resistance to malaria may exist in individuals suffering from blood disorders and those who have suffered "repeated attacks of malaria"; however, precautions to avoid mosquito bites should not be overlooked (CDC). Unfortunately, many misconceptions about malaria and its transmission exist. "Persons who were born in Nigeria are NOT protected against malaria, contrary to what many people think" (CDC).

"In 1998, the World Health Organization, UNICEF, the UN Development Programme and the World Bank came together in the Roll Back Malaria partnership, with the goal of halving the global burden of malaria by 2010...One of the objectives of Roll Back Malaria is to reduce malaria-related morbidity and mortality by 50 per cent in Nigeria by 2010, as well as to minimize the socio-economic impact of the disease" (UNICEF). This "intensive campaign" (lasting till December 2010) will distrubte "over 60 million nets...to around 30 million households during the campaign" (DFID). As part of this project, "over 800,000 Long Lasting Insecticide Nets and 55,000 long lasting insecticides kits for the re-treatment of mosquito nets have been procured and distributed by UNICEF in the past three years, with support from the Government of Japan" (UNICEF Nigeria).

Support Roll Back Malaria and its mission to reduce the number of malaria cases in Nigeria. You can also donate to Malaria No More to help provide mosquito nets to families who desperately need them.


Sources:

CDC. Malaria: Nigeria.

DFID [Department for International Development]. Nigeria gears up to roll back malaria.

Roll Back Malaria Partnership. Nigeria.

UNICEF. Nigeria: Together we can fight the scourge of malaria.

UNICEF. "Partnering to roll back malaria in Nigeria's Bauchi State."

Malaria in the UK

"Prepare for outbreaks of malaria," government agencies warn hospitals in the UK (Prince). Malaria is often considered a minor problem for the UK in modern times, but outbreaks are not unheard of and may become increasingly likely as global warming expands mosquito breeding grounds.

Hospitals must prepare for epidemics as they have been the site of malaria transmission in the past. In 1999 "two patients...contracted malaria while being treated at a hospital in Nottingham." The disease was transmitted from an infected patient in the hospital to the two other patients via a mosquito. That was "the second time there has been an outbreak of the tropical disease in a British hospital" (Malaria).

In 2008 reports of 1370 cases and 6 deaths from malaria were published in the UK (HPA). "A high likelihood of a major heat wave" may lead "to as many as 10,000 deaths, hitting the UK by 2012" warns the government (Prince). In coming years "the UK is to be hit by regular malaria outbreaks, fatal heat waves and contaminated drinking water within five years because of global warming, the Government has warned the NHS [National Health Service]" (Prince).

Malaria has been endemic in the UK before. "Malaria has been seen in these islands in the past" (Prince). "The marshlands of coastal southern and eastern England had unusually high levels of mortality from the sixteenth to the nineteenth century. The unhealthiness of the environment aroused frequent comment during this period and it was attributed to an endemic disease known as "marsh fever" or "ague"." This "marsh fever" is considered to be "malaria transmitted by anopheline mosquitoes. Malaria, once endemic in the coastal marshes of England, had a striking impact on local patterns of disease and death" (Dobson).

Malaria is present in the UK and outbreaks are not impossible. Heat waves from global warming may cause flooding and encourage mosquito breeding, but mosquito havens exist now. "The Thames Estuary has been identified as the likeliest place for a new outbreak of malaria, following an investigation by insect experts" (Thames). An outbreak of malaria may be possible even without the feared heat wave if such mosquito habitats are not addressed effectively.

"A spokesman for the Health Protection Agency said: Our work is based on what is likely to happen if we do nothing to prevent" the development of mosquito breeding grounds, "and it could well be that we see an increase in diseases such as malaria" (Prince).

The idea of a modern malaria epidemic in the UK is horrifying but preventable. "Better management and control of man-made sites where malarial mosquitoes may easily reproduce - such as water wells and bore holes - may help reduce malaria breeding close to human settlements" (Vector). Furthermore, home and land owners should take responsibility to prevent standing and stagnant water on their property. Fountains can be installed into ponds and lakes to agitate the water so that mosquitoes cannot breed. Even small amounts of standing water can serve as a nursery for the mosquitoes that transmit deadly malaria.

Sources:
Dobson MJ. Malaria in England: a geographical and historical perspective. 1994 August.
"Malaria outbreak at UK hospital" BBC. 29 March 1999.
Prince, Rosa. "Malaria Warning as UK becomes warmer." Telegraph.co.uk. 12 Feb 2008.
"Thames marshes 'perfect breeding grounds for malaria'." Evening Standard, The. 1 Feb 2002.
"Vector Control Tools..." The Health and Environment Linkages Initiative. http://www.who.int/heli/risks/vectors/malariacontrol/en/index3.html

Microchip detects malaria in Glasgow

"Scientists from Glasgow University claim they have created a device which can detect malaria within minutes." A microchip has been created to detect the malaria parasites in a blood sample. After the "blood samples are placed in the microchip" the device detects "the strain of disease. This means the best drug can be used to treat it." This method of detection is much better than previous methods because it is more accurate and faster (BBC).

"The current way of diagnosing is using a blood smear on a slide and examining it on a microscope," said project-leader Dr Ranford-Cartwright. "That will take a good microscopist a good hour to reach a diagnosis, it's extremely difficult to make that diagnosis accurately." This microchip "can give us a result in as little as half an hour."

Although malaria is less prevalent in the UK than in tropical regions of the world, it is not absent. "Last year a study revealed more cases of the most dangerous type of malaria than ever before are being brought back to the UK from trips abroad." Most malaria infections are imported, but the number of detected cases is rising. "The Health Protection Agency study identified 6,753 cases of falciparum malaria diagnosed between 2002 and 2006" (BBC).

Correct diagnosis is only one step toward malaria eradication. Another involves the development and use of effective drugs in the fight against the parasite. Ranford-Cartwright leads several research programs at the University of Glasgow including studies that examine the genetic markers for drug resistance. She says, "For this work we maintain different species of Anopheles mosquitoes in insectaries, and we infect them with P. falciparum sexual stages grown in culture. We use genetic techniques to study complex traits such as the interaction between the malaria parasite and its mosquito vector. We are also involved in work to identify factors important in the spread of anti-malarial resistance" (Ranford-Cartwright). "There is" further "need for a specific, sensitive, robust, and large-scale method for diagnosis of drug resistance genes in natural Plasmodium falciparum infections" (Abdel-Muhsin).

Sources:
Abdel-Muhsin, AM. LC Ranford-Cartwright, et al. "Detection of mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) gene by dot-blot hybridization." Am. J. Trop. Med. Hyg., 67(1), 2002, pp. 24-27

BBC News. "Doctors welcome Malaria Microchip." 24 April 2009.

Ranford-Cartwright, Lisa. "Research Interests." University of Glasgow. 7 August 2009.

Malaria in Cambodia

Researchers recently announced that a strain of malaria parasite in Cambodia has become resistant to "arteminisnin-based drugs". This development "could put millions of lives at risk" (Resistance). "Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance" (Dondorp).

"Choloroquine and sulfadoxine-pyrimethamine resistance in P.falciparum emerged in the late 1950s and 1960s on the Thai-Cambodian border and spread across Asia and then Africa, contributing to millions of deaths from malaria. "Since the first reports of chloroquine-resistant falciparum malaria in southeast Asia and South America...drug-resistant malaria has posed a major problem in malaria control. By the late 1980s, resistance to sulfadoxine-pyrimethamine and to mefloquine was also prevalent on the Thai-Cambodian and Thai-Myanmar (Thai-Burmese) borders, rendering them established multidrug-resistant (MDR) areas" (Wongsrichanalai).

"Artemisinins have been available as monotherapies in western Cambodia for more than 30 years, in a variety of forms and doses, whereas in most countries...they have been a relatively recent introduction." An "extended period of often-suboptimal use, and the genetic background of parasites from this region, might have contributed to the emergence and subsequent spread of these new artemisinin-resistant parasites in western Cambodia." "In contrast, artemisinin derivatives have been used almost exclusively in combination with mefloquine on the Thai-Burmese border, where parasitologic responses to artemisinins remain good, even after 15 years of intensive use" (Dondorp).

The recent study compared patients from Cambodia with those from Thailand. "Researchers (Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Program) discovered that on average "patients in Thailand were clear of malaria parasites within 48 hours" but Cambodian patients averaged 84 hours" (Resistance). "These markedly different parasitologic responses were not explained by differences in age" and "adverse events were mild and did not differ significantly between the two treatment groups" (Dondorp). Dr Arjen Dondorp declared, "Our study suggests that malaria parasites in Cambodia are less susceptible to artemisinin than those in Thailand". Currently, artemisinin is used to "clear the parasites at an early stage, preventing them further maturing and reproducing" (Resistance). Since its introduction, "artemisinin-based combination therapies has reduced the morbidity and mortality associated with malaria" (Dondorp).

However, with the new emergence of resistant malaria parasites, the number of malaria related deaths is expected to rise. "Measures for containment are now urgently needed to limit the spread of these parasites from western Cambodia and to prevent a major threat to current plans for eliminating malaria"(Dondorp). "Sixty percent of Cambodia's landscape poses a malarial risk. One million Cambodians are infected with malaria each year" (Wongsrichanalai). "Malaria remains one of the primary causes of mortality in Cambodia... Sustained efforts through local and national malaria control will be necessary to contain Cambodia's malaria epidemic" (Wongsrichanalai).

Image from Donorp. Graph from comparative study between Cambodia and Thailand, and how well the drugs treat malaria.


Sources:
Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2009;361:455-467.
Population Reference Bureau. "Fewer Malaria Cases in Cambodia."
"Resistance to Malaria Drug Reported in Cambodia." US World News. 29 July 2009.
Wongsrichanalai C, Pickard AL, et al. Epidemiology of drug-resistant malaria. 2002 Apr.