By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Malaria mortality in Africa has decreased by approximately 57% during the past 15 years, but some areas still have low level use of bed nets, low coverage with antimalarial medication, and higher death rates due to malaria. At the same time, anti-malarial measures are still important for individuals traveling to endemic areas.

SOURCE: Gething PW, Casey DC, Weiss DJ, et al. Mapping Plasmodium falciparum mortality in Africa between 1990 and 2015. N Engl J Med 2016;375:2435-2445.

Efforts to quantitate the morbidity and mortality of malaria have been hampered by limited reporting and by geographical variations in the incidence and severity of malaria. Gething and colleagues provided careful spatiotemporal modeling to develop accurate quantitative data about the risk of death due to malaria across age spans and geography in Africa. They used material from the Malaria Atlas Project and the Global Burden of Disease Study.

The number of deaths due to malaria increased from 1990 until 2000. Then, from 2000 to 2015, the rate of deaths due to malaria decreased 57% from 12.5 to 5.4 per 10,000 people. As populations were increasing, this led to a 37% decrease in the total number of malaria deaths each year — from 1,007,000 in 2000 to 631,000 in 2015. In areas where malaria was more common, more than 80% of malaria deaths were in preschool-aged children, while older children and adults were at greater relative risk of death in areas where malaria was less common.

A few specific countries were responsible for high death rates due to malaria, and these were countries where fewer than half of households used insecticide-treated bed nets and where antimalarial medications were less available. These countries were largely in the western parts of sub-Saharan Africa and included Nigeria, Angola, Cameroon, Congo, Guinea, Equatorial Guinea, and parts of Central African Republic.

COMMENTARY

Malaria continues to be a major problem for children in Africa, accounting for nearly as many deaths each year as pneumonia. Fortunately, as shown by the modeling techniques of Gething and colleagues, the death rate due to malaria has dropped to less than half of what it was 15 years ago. This is encouraging, especially in view of the extensive multinational efforts to combat malaria that are estimated to have cost $2.3 billion in 2015.

Even for those of us not living in Africa, though, our care of international travelers keeps malaria relevant. Since the epidemiology of malaria is evolving in many areas of the world and since other illnesses also are more common in malaria-endemic areas, travelers can be directed to pre-travel consultation at specialized travel clinics. Geographic registries of travel clinics are available from the American Society of Tropical Medicine and Hygiene (http://www.astmh.org/education-resources/clinical-consultants-directory) and the International Society of Travel Medicine (http://www.istm.org/AF_CstmClinicDirectory.asp). Healthcare professionals who choose to care for travelers can get updated information about malaria prevention in specific regions of the world from the Centers for Disease Control and Prevention (https://www.cdc.gov/malaria/travelers/index.html) or from commercial services.

Malaria chemoprophylaxis is indicated for travelers to malaria-endemic areas.1 Chloroquine is effective against malaria in Central America and the Caribbean, but is often unavailable in the United States. Worldwide, mefloquine may be given weekly starting one to two weeks prior to travel and continuing weekly through the trip and for four subsequent weeks; altered sleep and nausea can occur in approximately 18% of recipients of mefloquine prophylaxis. Atovaquone-proguanil is effective in daily dosing beginning one day before arrival in a malarial area and continuing through seven days after leaving the malarial area. Both mefloquine and atovaquone-proguanil may be given to children using weight-adjusted dosing. Doxycycline is effective and is generally safe in children of at least 8 years of age; it is given daily beginning one day prior to entry into a malarial area and continuing through 28 days after leaving the area of risk.

Effective malaria prevention, of course, depends on more than just medication. Also, Aedes mosquitoes can transmit dengue, chikungunya, Zika, and yellow fever in some of the same areas where Anopheles mosquitoes transmit malaria. Mosquito bite prevention is effective with application on exposed skin of insect repellants containing di-ethyl-meta-toluamide (DEET) or picaridin with 20-30% preparations adequately repelling mosquitoes for approximately six hours. Clothes can be sprayed or impregnated with permethrin to provide additional protection. While Aedes often bite during the daytime, Anopheles bite more frequently from dusk to dawn; sleeping under bed nets or in air-conditioned rooms with closed/screened windows reduces the risk of nighttime bites.

Progress continues with malaria vaccine deveFlopment. Lives can be saved with pediatric vaccination, but efficacy is less than 50%.2 Follow-up vaccine studies suggest that malaria immunity wanes over time after vaccination.3,4

Febrile tourist travelers and immigrants who recently have been in malarial areas can benefit from rapid diagnosis (with blood smears by experienced laboratory technicians or by polymerase chain reaction testing). If test results are positive or clinical suspicion is high pending results, prompt treatment with artemisinin combination therapy (such as artemether-lumefantrine) is effective.

Even as malaria is being rolled back from some regions of the world and even as diagnostic and therapeutic measures improve, there are increasing concerns about the development of insecticide resistance in mosquitoes and about the possibility that resistance of malaria parasites to the effects of artemisinin derivatives might spread from localized areas of Asia to Africa.3 As evident by Gething’s data, lower rates of malaria death are seen in areas with greater bed net use and more availability of antimalarial medication. Multifaceted interventions still are needed to help those most in need, the children of Africa.

REFERENCES

  1. Freedman DO, Chen LH, Kozarsky PE. Medical considerations before international travel. N Engl J Med 2016;375:247-260.
  2. Callaway E, Maxmen A. Malaria vaccine cautiously recommended for use in Africa. Nature 2015;526:617-618.
  3. Maitland K. Severe malaria in African children — the need for continuing investment. N Engl J Med 2016;375:2416-2417.
  4. Olotu A, Fegan G, Wambua J, et al. Seven-year efficacy of RTS,S/AS01 malaria vaccine among young African children. N Engl J Med 2016;374:2519-2529.