Global Health Interventions: A Review of the Evidence Background Methodology • Glossary

Malaria

Infectious Diseases

Other Health Conditions

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See a detailed Key Findings table for estimated risk reduction and strength of evidence.

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See a detailed disease logic model to better understand disease acquisition, progression, and opportunities for intervention.

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Overview: Malaria

Disease Background

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. The Plasmodium protozoa have four species, of which falciparum is the most deadly and vivax is common in certain regions but less dangerous.

Symptoms of malaria include fever, headache, and vomiting. They usually appear 10-15 days after the mosquito bite. If untreated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. In many parts of the world, the parasites have developed resistance to a number of malaria medicines.[1]

Epidemiology

  • Malaria is the 5th leading cause of death from infectious diseases worldwide (after respiratory infections, HIV/AIDS, diarrheal diseases, and tuberculosis).[1]
  • It is the 2nd leading cause of death from infectious disease in Africa, after HIV/AIDS.[1]
  • 3.3 billion people (half the world’s population) live in areas with malaria risk, in 108 countries and territories. [2]
  • WHO estimates that in 2008 malaria caused 243 million clinical episodes, and 863,000 deaths.[1]
  • 35 countries (30 in sub-Saharan Africa and 5 in Asia) account for 98% of global malaria deaths.[1]
  • Pregnant women have increased susceptibility to Plasmodium falciparum malaria; in malaria-endemic countries, P. falciparum contributes to 8-14% of low birth weight, which decreases the chance of a baby’s survival.[1]
  • Malaria cuts economic growth by as much as 1.3% in countries with high disease rates. [3]
  • Malaria is more common in rural areas than in cities. [4]
  • Co-infection with HIV and malaria increases mortality [5]
  • Malaria is preventable and curable.

The intervention assessments below summarize evidence presented in the "Key Findings" table.

 

Prevention: What Works?

There are three major categories of prevention for malaria: reducing the number of mosquitoes, reducing mosquito-human contact, and providing drugs. Other prevention strategies for which evidence is lacking are noted below.

  • Reducing the number of mosquitoes. Environmental modification or manipulation for vector control alters the environment (land, water, or vegetation) to deprive the mosquito of its requirements for survival. These interventions appear to reduce malaria incidence by 80-88%, based on many studies, though the evidence underlying these estimates is rated as weak due to the lack of randomized trials.
  • Reducing mosquito-human contact. Interventions that keep potentially infected mosquitoes away from humans are effective:
    • Long-lasting insecticide-treated bed nets (LLIN). LLIN reduce the number of human bites. They reduce overall child mortality by 17-23% (very strong evidence) and reduce malaria incidence by 45% (weak evidence). For pregnant women, LLIN reduce parasitemia and anemia during pregnancy, and low birth weight, by 10 - 30% (very strong evidence).
    • Indoor residual spraying (IRS). IRS is the application of long-acting chemical insecticides on the walls and roofs of houses and domestic animal shelters, to kill adult mosquitoes that land on these surfaces.[6] IRS reduces incidence by 14-54% (moderate strength evidence), with effectiveness apparently better in settings with fewer infectious mosquito bites per year. LLIN appears to work better than IRS (RRR 18-32%; weak evidence).
  • Drugs. Antimalarial drugs provide good protection for high risk groups. During pregnancy, drug regimens (often IPTp, Intermittent Preventive Treatment in Pregnancy) reduce perinatal infant mortality by 27% (strong evidence), clinical malaria in the mother by 58% (weak evidence), and parasitemia in the mother by 47-88% (strong evidence). Evidence for other outcomes (eg, maternal anemia and stillbirth) is equivocal (not in table). Preventive drug regimens reduce clinical malaria in children by 28-53% (strong evidence). For dormant vivax malaria, including primaquine in the drug regimen for 2 weeks reduces parasitemia by 59-89% (strong evidence). Although we focus on ACTs as treatment (below), they may also bolster prevention.[7]
  • Other (not in table). Other malaria prevention strategies may be effective in certain circumstances, but lack substantial quantitative evidence of clinical or parasitological benefit. These include: 
    • Vaccines: Intensive efforts are underway to develop vaccines that reduce infection, clinical severity, or both. At present no vaccine confers durable and high benefit. The most successful candidate is RTS,S, found to reduce malaria episodes by 4-63% for 18 months.[8]  Other vaccines show no significant benefit. 
    • Personal protection: Window screens; electronic repellents (a review found no effect[9]), insect repellents applied to skin or other surfaces; light-colored clothes, long pants and sleeves; and coils (a review found fewer bites.[10]).
    • Source reduction-larval control: Oils applied to the water surface, suffocating the larvae and pupae; biological control agents applied to water; mosquito fish. Fogging or area spraying: Mainly used for emergencies: halting epidemics or adult mosquitoes at severe pest levels.
    • Sterile male release: successfully used in small-scale areas; impractical for large areas due to large mosquito numbers needed.
    • Integrated Vector Management[11]: Decision-making process to manage interventions rather than an intervention in itself.
    • Case-finding in situations of well-controlled low endemic malaria.

Treatment: What Works?

Treatment for malaria relies primarily on anti-malarial drugs, which attack parasites in the blood. The oldest drugs are chloroquine and related compounds, for which resistance is high in some countries and regions. The newest are artemisinin-based combination therapies (ACTs), of which four are currently recommended by WHO, and resistance is still low. For severe disease, standard supportive therapy (e.g., fluid replacement) is also important, and not reviewed here.

  • Drugs for uncomplicated disease. ACTs are widely accepted to work far better than the older chloroquine regimens. Thus, we could find no formal review of this comparison. Evidence takes other forms: ACT treatment success (by PCR test) is >90%. [12] Community roll-out of ACTs leads to a sharp drop (e.g., 52-75%) in malaria cases and mortality. [13]
    Formal reviews focus on other important issues. ACTs reduce treatment failure by 67-88% versus alternative non-chloroquine regimens in most settings (not in West Africa, where resistance to the alternative regimens is low; strong evidence). Newer ACTs appear statistically no different than older ones (moderate strength of evidence). According to the WHO, the choice of ACT should be based on the efficacy of the non-artemisinin drug in the geographic area of intended deployment, e.g., primaquine where vivax is present.[14]
  • Drugs for complicated disease. Artemisinin drugs are also preferred for management of severe disease, which requires non-oral delivery (e.g., intravenous or rectal). Compared with quinine, artemisinin derivatives reduce mortality by 10-38% (strong evidence). They have an unclear effect on neurological sequelae (-663-36%) (moderate strength of evidence). One trial found that rectal artesunate for patients unable to take oral medicine prior to referral to a clinic reduced death or permanent disability by half for those more than 6 hours from the clinic.[15]
  • Other (not in table). No identified reviews reported clinical outcomes for persons who are infected with HIV, although we identified two Cochrane review protocols. WHO provides guidelines for this important sub-group[16].

Summary / Future Directions

Prevention. The long-lasting insecticide-treated bed net (LLIN) is an effective, practical mainstay of malaria prevention. Benefit is also provided by environmental modification, indoor residual spraying, and drugs for high risk groups. A huge reduction in global incidence of this deadly disease could be achieved with rapid deployment of these interventions.

Treatment. Artemisinin-based combination therapy (ACT) similarly represents a major advance and highly effective tool to fight malaria. ACTs and other regimens together offer a strong treatment portfolio, although drug resistance will likely limit utility of current drugs over time.

The future requires and promises technological advances in multiple areas. Results from vaccine trials, especially of RTS,S, confirm that it is possible to develop a malaria preventive vaccine. Currently, more than 30 vaccine candidates are under development. The Malaria Vaccine Technology Roadmap, a prominent malaria vaccine development consortium supported by multiple donors, is committed to developing a malaria vaccine by 2025 with protective efficacy of at least 80% against clinical disease, for at least four years.[17]

In parallel, there are efforts to assure prevention options remain viable and expand. The potential impact of insecticide resistance, particularly on LLINs, is being monitored and new insecticides brought on line as needed. Other developments include transgenic mosquitoes, larviciding in urban areas, and utilizing cost-effective consumer products. [18]

Strategies to sustain treatment include lowering the cost of manufacturing artemisinin by harnessing microbes to make a key precursor chemical, and developing new therapeutic agents in anticipation of the emergence of ACT-resistant parasites.[19] In addition, major efforts are underway to make ACT regimens available and usable, such as more convenient pediatric formulations. The Millennium Development Goal Target 6c is to “Halt and begin to reverse the incidence of malaria and other major diseases.” Nearly 40 countries have reduced malaria burden by at least 50% since 2000 with programmatic scale up.[20] Scaled-up application of existing and new interventions will extend these successes.

References

1. WHO. Health topics: Malaria. 2011. Available from: http://www.who.int/topics/malaria/en/.

2. CDC. Malaria Facts. 2010. Available from: www.cdc.gov/malaria/about/facts.html

3. WHO. Media Centre: Malaria. Fact Sheet No. 94, April 2010. Available from: http://www.who.int/mediacentre/factsheets/fs094/en/.

 

4. Wikipedia. Malaria, citing: Breman J. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg. 2001 Jan 1; 64 (1-2 Suppl): 1–11.

5. Wikipedia. Malaria, citing: Korenromp E, Williams B, de Vlas S, Gouws E, Gilks C, Ghys P, Nahlen B. Malaria attributable to the HIV-1 epidemic, sub-Saharan Africa. Emerg Infect Dis. 2005; 11 (9): 1410–9.

6. WHO. Malaria: Indoor residual spraying. Available from: http://www.who.int/malaria/vector_control/irs/en/index.html.

7. Okell LO, Drakeley CJ, Ghani AC, Bousema T, Sutherland and CJ. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malaria Journal. 2008; 7:125. DOI:10.1186/1475-2875-7-125.

8. Graves PM, Gelband H. Vaccines for preventing malaria (pre-erythrocytic). Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006198. DOI: 10.1002/14651858.CD006198.

9. Enayati A, Hemingway J, Garner P. Electronic mosquito repellents for preventing mosquito bites and malaria infection. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005434. DOI: 10.1002/14651858.CD005434.pub2.

10. Lawrance CE, Croft AM. Do mosquito coils prevent malaria? A systematic review of trials. Journal of Travel Medicine. 2004; Mar-Apr;11(2):92-6.

11. WHO: Malaria: Integrated vector management. Available from: http://www.who.int/malaria/vector_control/ivm/en/index.html.

12. Sinclair D, Zani B, Donegan S, Olliaro P, Garner P. Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007483. DOI: 10.1002/14651858.CD007483.pub2.

13. Bhattarai A, Ali AS, Kachur SP, Mårtensson A, Abbas AK, et al. Impact of Artemisinin-Based Combination Therapy and Insecticide-Treated Nets on Malaria Burden in Zanzibar. PLoS Med. 2007; 4(11): e309. doi:10.1371/journal.pmed.0040309.

14. WHO. World Malaria Report 2008. Box 2.1; WHO recommendations for the diagnosis and treatment of malaria. Available from: http://www.who.int/malaria/publications/atoz/9789241563697/en/index.html

15. Gomes M et al. Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet, 2009; 373 (9663): 557-566.

16. WHO. Malaria and HIV/AIDS interactions and their implications for public health policy: Report of a technical consultation. 2004, Jun 23-25. Available from: http://www.who.int/malaria/publications/atoz/9241593350/en/index.html.

17. WHO. Media Centre: Global strategy aims for effective malaria vaccine by 2025. 2006, Dec 4. Available from: http://www.who.int/mediacentre/news/notes/2006/np35/en/index.html.

18. Enayati A. Malaria Management: Past, Present, and Future. Annual Review of Entomology, Vol. 55 (Volume publication date January 2010); Review in Advance first posted online on September 15, 2009. Available from: http://arjournals.annualreviews.org/doi/abs/10.1146/annurev-ento-112408-085423?url_ver=Z39.88-2003.

19. Harvard School of Public Health. Future of malaria research focus of half-day symposium at HSPH. 2007, May 25. Available from: http://www.hsph.harvard.edu/now-archive/20070525/malaria.html.

20. WHO. World Malaria Report 2009. December 2009. Available from: http://www.who.int/malaria/world_malaria_report_2009/en/index.html

-- Updated June 2011