The Scourge of Travelers: Malaria

By Alice Zal, DO, FACOFP

ABSTRACT: Malaria remains one of the most important diseases in the world. There are 300 to 500 million cases each year causing 1.5 to 2.7 million deaths. In the United States the imported cases top 1,500 per year. Chemoprophylaxis and rapid diagnosis and treatment are the keys to decreasing its morbidity and mortality. Few civilizations have escaped the perils of this disease - Egyptian mummies have signs of the disease, Hippocrates documented the distinct phases of the disease, Alexander the Great most probably died of it and so the demise of the Greek Empire. The American Civil War and World War II had many casualties from this scourge. Now is the time to control, if not eradicate, this worldwide epidemic.1

As worldwide travel opportunities are more numerous, the spread of diseases across borders has increased rapidly. Nearly 1,500 new cases of Malaria occur in the United States each year. Approximately 60 percent are among U. S. travelers, even though there are many preventative medical treatments available. Travelers often fail to take or adhere to recommended chemoprophylaxis, fail to seek medical care promptly for post-travel illnesses, and experience a failure of rapid diagnosis and treatment of suspected Malaria cases. These factors all contribute to an avoidable increase in fatal outcomes from a treatable disease.2

Case Study
A 35-year-old black female came to the Emergency Department of an urban hospital with the com­plaint of two days of myalgias, cough and fever with increasing shortness of breath. Her past medical history was not significant and she had no prior surgical history. Her social history included being a married mother of a ten-year-old healthy son and working as a Social Worker at a clinic. She had a negative history for tobacco use, alcohol or drug abuse. When asked by the admitting doctor if she had been away on vacation she said, “No.” She was admitted to the hospital for pneumonia and placed on I.V. Rocephin and Zithromax, while cultures and antibody titers were pending.

When her primary care physician came to see her she was asked about vacations once again, but was also asked if she visited her family recently. Sometimes asking a question a different way can be very fruitful. The patient came from Nigeria and did indeed visit her relatives for four weeks recently. She did not consider this a vacation. Immediately a thick blood smear was sent to the laboratory ... it was read as positive for Plasmodium falciparum.

Introduction
Malaria remains one of the most serious infec­tions facing mankind. It is a parasitic infection produced by four species of Plasmodium: P. vivax, P. falcipa­rum, P. ovale, and P. malariae. The transmission of this parasite to humans is via the Anopheles mos­quito. Once a person is infected, the parasite (sporo­zoite) travels to the liver parenchymal cells where it matures (merozoite). It then enters the circulatory system and becomes incorporated into the erythro­cyte (trophozoite) until it ruptures the erythrocyte. It is during this phase that patients present with paroxysms of chills, fever and sweats, along with anemia and eventually splenomegaly and a chronic relapsing course. If left untreated it can escalate to pneumoniae or cerebral malaria that can lead to brain damage, with an increased mortality rate.

Malaria occurs mainly in the tropical areas of the world, where the anopheles mosquito thrives. These areas include Mexico, Haiti, Central America, South America, Africa the Middle East, the Indian subcontinent, Southeast Asia, Korea, Indonesia and Oceana. Prior to the 1940’s it also was prominent in parts of the United States and Europe, where warm moist climates occurred.

During WWII, the WHO focused on vector control to eradicate this disease from infecting soldiers as they marched through Europe. Wide spraying of a new insecticide (DDT) was used. It was utilized in the swampy and stagnant water bodies in the areas of disease transmission. Swamps were drained, forests and fields were dusted and millions of homes were sprayed, with the hope of eradicating the disease totally. However, it was not long before insecticide resistant mosquitoes and drug resistant parasites began to emerge.
In the 1960’s hopes of eradicating the disease were abandoned and efforts were initiated to control the disease itself. Presently The Bill and Melinda Gates Foundation is actively working on a variety of Malaria Programs.3

Disease Control
Today 3.2 billion people are at risk of Malaria, with 350 million to 500 million clinical cases worldwide.1,3 More than a million deaths occur each year with over 80 percent of these deaths targeting African children under five years of age. Attempts to control the vectors and treat the disease remain an uphill battle. Many of the highest disease areas are in isolated regions far from the nearest health care facilities in Africa and other tropical nations of the world.4

Distribution of DEET (N,N-diethylmeta­toluamide) or permethrin impregnated bed nets and spraying homes and swampy land areas with DDT are only a small part of the attempt to eradicate this disease. It is nearly impossible to get these products to remote areas, making it difficult for people in hot and highly humid climates to cover themselves during a night of sweaty sleep. Even one foot out of the protective netting can expose a young child or a parent to the bite of the female anopheles mosquito. Hence, with all the good intentions of suppliers and the desire of parents to protect their children, efforts sometimes fail.

Two incidental medical conditions may be protective against the hemolytic phase of Malaria: sickle cell disease and glucose-6-phopsphate dehydrogenase deficiency. In areas where Malaria is prevalent due to national selection for survival there is the highest concentration of populations with these conditions. The hemolytic merozoite phase can not develop and perpetuate the clinical disease in people with sickle cell disease or those with G6PD deficiency, due to the fragility of the erythrocyte.

Many pharmaceutical companies and organizations have invested in the development of a vaccine against Malaria. The Malaria vaccine development is very complicated. The main problem is which stage of the parasite’s life cycle to target. The Malaria Vaccine Initiative (MVI) has a lot of governmental and private funding. The goal is to find the various antigens of the different parasitic phases and combine them in a vaccine against the disease. Another challenge is that multiple Malaria infections can be present in the same Host simultaneously. Finally the parasite causing this infection has a very intricate genetic code. For example the Polio virus consist of 11 genes, whereas Plasmodium falciparum has more than 5,000 genes. Hence, creating a Malaria Vaccine may prove to be one of the most energetic medical quests of all time.1,5

Chemoprophylaxis
Prior to traveling outside the United States any knowledgeable person or travel agent should advise the Traveler to “Consult the Yellow Book” published by the CDC. The risk to travelers is variable even for people traveling to the same regions. Living in an air-conditioned hotel is considerably safer than backpacking or adventure traveling. Even short stops on a cruise ship can expose travelers to the perils of the Anopheles mosquito. Hence, all persons traveling to malaria-endemic areas should take chemoprophylaxis and use anti-mosquito measures as well. There is still a risk of contracting malaria with implementation of these measures.

Chemoprophylaxis is a strategy that utilizes medication prior to, during and after the exposure period to prevent the disease caused by the malaria parasite. One must be aware of resistance to drugs in various area, and tailor the regime appropriately for a particular travel itinerary.6

If traveling to an area where chloroquine is effective it can be taken once a week. Other alternatives in these areas are hydroxychloroquine (Plaquenil), doxycycline, mefloquine or atovaquone/proguanil. Each drug has its own time line, but for chloroquine it should start two weeks prior to travel and continue for four weeks after returning. For travel to areas where there is chloroquine-resistance the choices are: atovaquone/proguanil (Malarone) starting two days prior to travel and to continue daily until seven days after returning; Doxycycline starting two days prior to travel and continue for four weeks after returning, and; Mefloquine (Lariam) starting two weeks prior to travel once a week and to continue for four weeks upon return from endemic areas. Another choice for both resistant and non-resistant areas is Primaquine. However special precautions must be taken when administering this drug. Persons with a G6PD deficiency can develop hemolysis, which can be fatal (Note: testing for normal G6PD levels must be done prior to its administration.). Special considerations should be given to infants, young children, pregnant women and nursing mothers. These choices and updates for chemoprophylaxis can be reviewed at www.cdc.gov/travel/yellowbook.

Treatment
Upon return from endemic areas, travelers may experience signs of sweats, fever , myalgias and other symptoms. as early as seven days (P. falciparum) or up to four weeks for relapsing malaria (P. ovale or P. vivax). Rapid malaria tests7 may be a useful diagnostic adjunct to microsopic identification. However, expert microscopy is still required for species identification and confirmation and it is not readily available in the United States. Once confirmed it must be reported to the CDC. Early recognition of the disease and early treatment can mean the difference between survival and death.

In the United States the drug of choice to treat severe malaria is intravenous Quinidine gluconate. If a patient can not tolerate this drug, artemisinin derivatives (Malarone) are also efficacious.

Conclusion
Malaria can be difficult to diagnose. Time is of the essence for decreasing the morbidity and mortality associated with this disease. A travel history is an essential aspect in the health history of a patient. Do not assume compliance with chemoprophylaxis regimens. Do not hesitate to get a thick blood smear in anyone you suspect the disease and repeat it on three different occasions (only the hemolytic phase of the parasite’s life cycle will appear on slides.) Once a confirmation is done report it to the CDC and quickly treat the patient. 

Dr. Zal graduated from PCOM in 1989. She is certified in family practice and manages a practice in Norristown, Pennsylvania. She is on the staff of Mercy Suburban Hospital, Montgomery Hospital, and the Hospital of the University of Pennsylvania. She is a Fellow of ACOFP and won the Crest Award. She is the winner of the March of Dimes Physician of The Year.

References

  1. Finkel, Michael. Bedlam in the blood-Malaria. July, 2007, National Geographic.
  2. Newman, Robert, M.D.,Parise, Monica,M.D.,Barber, Ann, B.A. and Steketee, Richard, M.D. Malaria-related deaths among U.S. travelers 1963-2001. Annals of Internal Med., Oct, 2004. 141 (7), 547-555.
  3. Loewenberg, Samuel. The U.S. President’s Malaria initiative: 2 years on. The Lancet, Dec, 2007, 370, 1893-1896.
  4. Dorsey, Grant, M.D., Gandhi, Monica, M.D., Oyugi, Jessica, M.D. andRosenthal, Philip, M.D. Difficulties in the prevention, diagnosis and treatment of imported Malaria. Arch. Int. Med, Sept, 2000. 160, 2505-2510.
  5. Ekolaq Dye, Amy and Hooks, Carol. U.S. Army joins forces with Malaria vaccine initiative to launch clinical trial in Kenya. U.S. Army, April, 2002. 020425.
  6. Center for Disease Control and Prevention. Travelers Health: Yellow Book. 2008, chapter 4, Malaria.
  7. Marx, Arthur, M.D., Pewsner, Daniel, M.D., Egger, Matthias, M.D. et al. Meta-analysis: Accuracy of rapid tests for Malaria in travelers returning from endemic areas. Annals of Internal Med., May, 2005. 142 (10), 836-847.

Sources Not Referenced