Over the past decade there has been renewed momentum with significant resources provided from the Global Fund for HIV, Malaria and Tuberculosis and the Bill & Melinda Gates Foundation. This has led to considerable progress towards reducing the overwhelming burden of malaria, including substantial declines in mortality [1]. However, the gains have been uneven and must be viewed with caution given inadequate surveillance and suboptimal data. Moreover, current control approaches should be approached within the context of the previous major global effort to eradicate malaria that was aggressively and optimistically pursued in the period from 1955 to 1969 [2]. While the initiative achieved important successes, including elimination of malaria in some countries and significant reduction in other areas such as India and Sri Lanka, many regions realized negligible progress. Unfortunately, a convergence of factors, including emergence of chloroquine resistance, vector resistance to insecticides, difficulties of sustaining funding, conflicts, and population movements, coupled with inadequate community participation and operational issues, resulted in lost momentum with a subsequent major recrudescence of the disease. Ultimately, in areas of significant malaria transmission, integrated and sustained approaches with commitments for adequate funding will be necessary. [3]
The goals of reducing the impact of malaria can range from control, which targets reduction of the impact of malaria, to elimination, an approach that seeks to completely remove the disease from areas, to the lofty notion of total global eradication. There is continuing debate among acknowledged experts on the best anti- malaria strategy to pursue and any such Herculean effort benefits from the involvement of both pragmatists and idealists.
The epidemiology of malaria is exceedingly complex, formed by the interaction of agent, vector, host, and environment as well as political and socioeconomic factors. As a result, in most endemic areas malaria control requires knowledge of the local epidemiology and biology. Current control strategies can incorporate a broad array of approaches that include insecticide-treated nets (ITNs), indoor residual spraying (IRS), source reduction that targets mosquito breeding areas, area application of insecticide, intermittent preventive treat- ment (IPT) of pregnant women, children, and infants, identifying and treating cases, personal protective measures, and education.
Vector Control:
Control of anopheline vectors is a key component of efforts to reduce the burden of malaria and there are a number of effective approaches available.
Insecticide-Treated Nets:
ITNs that are impregnated with pyrethroid preparations (typic- ally deltamethrin or permethrin) provide a physical barrier and repellent for mosquito protection and also act to reduce vector longevity and vector populations. Studies have demonstrated that ITNs result in declines in mosquito populations and reduced burden of malaria. ITNs lowered the risk of childhood mortality by 17 per cent compared to no nets and 23 per cent to untreated nets. In areas of stable malaria, ITNs reduced the incidence of uncomplicated malaria episodes by 50 per cent compared to no nets and 39 per cent compared to untreated nets [4]. The benefits for preventing malaria in pregnancy have also been established. In Africa, ITNs reduced placental malaria and low birthweight by over 20 per cent and fetal loss in the first to fourth pregnancy by over 30 per cent. Moreover, when ITN coverage is sufficiently high, indirect benefits can be observed for others in the community not using nets. [5]
Historically, ITNs required retreatment at 6–12-month periods, but compliance with retreatment is low. However, newer, long-lasting insecticidal nets (LLINs) with insecticide incorporated into the fabric of the netting provide residuals of 3–5 years’ duration. While costlier to produce, these nets overcome the need to repeatedly retreat and are increasingly available. Barriers to the use of ITNs include discomfort, primarily from heat, cost, and availability. [6]
Indoor Residual Spraying:
IRS is an effective means of vector control for mosquitoes and was an important component of the WHO’s Global Malaria Eradication Programme from 1955 to 1969. Residual insecticide with prolonged residual activity is applied to interior walls and roofs of dwellings. Given that many of the major malaria vectors, such as An. gambiae in Africa, feed at night and exhibit indoor resting (endophilic) and indoor feeding (endophagic) behaviour, IRS has demonstrated considerable success. The approach has been responsible for major effects in the control and elimination of malaria including past successes in areas of Asia, Russia, Europe, Latin America, and parts of Africa [7]. IRS products include pyrethroid-class compounds, organophosphates, and carbamates. Although previously abandoned as a result of environmental concerns, the organochlorine pesticide DDT has been increasingly used in recent years and is viewed as a valuable product due to its long residual [8]. Effective use of IRS requires knowledge of local vector behaviour and possible resistance patterns, cooperation and acceptance by residents to ensure adequate coverage, and effective logistics. Most currently applied insecticides are pyrethroids, which have low mammalian toxicity, and DDT.
Source Reduction/Environmental Management:
Source reduction involves the elimination of water sources that serve as breeding sites for mosquitoes. This can involve draining or filling in standing water, swamps, or marsh areas, emptying or covering containers such as pots, cans, or rain barrels that can hold water and serve as sites for breeding, and intermittent irrigation. Source reduction played a key role in the control of malaria in the Panama Canal Zone, peninsular Malaysia, and the Indonesian archipelago [9]. Such efforts can be very resource intensive and the widely dispersed nature of water sources, the difficulty in identifying all water sources, and determining where and when smaller water sources will be established, make the approach challenging. Moreover, many anopheline mosquitoes are opportunistic breeders that favour small streams and rivulets and the capacity of major vectors such as An. gambiae to breed in small temporary pools of water prevent the wide application of this technique. Other means of targeting the aquatic larval stage of mosquitoes include applying oils to the water surface which prevents larvae and pupae from obtaining air. Most oils currently used for such purposes are biodegradable. [10]
Biological Control:
Toxins from Bacillus thuringensis var. israelensis (BTI) and insect growth regulators such as methroprene can also be applied to water sources for larval control. The use of BTI has demonstrated recent success against malaria vectors and may prove useful in integrated approaches to vector management. Bacteria, such as Wolbachia, are known to make vectors refractory to a variety of human pathogens. Studies have reported the establishment of a stable Wolbachia infection in an important malaria vector, Anopheles stephensi, that conferred resistance to P. falciparum [11]. In addition, an Enterobacter species has been identified that inhibits development of the malaria parasite in An. gambiae. Biological controls such as the mosquito fish (e.g. Gambusia affinis), fungi (e.g. Laegenidium giganteum), and parasitic nematodes (e.g. Romanomermis culicivoras) have not been widely employed. [12]
Fogging or Area Spraying of Insecticides:
More widespread application of insecticides is primarily used in emergency situations such as epidemics and targets adult mosquitoes. Insecticide must be repeatedly applied and timed appropriately during peak periods of adult activity since it may be difficult for the insecticide to reach areas where mosquitoes are resting.
Release of Sterile Male Mosquitoes:
Introducing sterile male mosquitoes has been successful in small-scale studies; however, the large numbers necessary limits are applicable to most areas. [13]
Genetic Modification of Malaria Vectors:
The use of genetic modification to develop mosquitoes that are refractory to malaria infection is an appealing concept. Such modified mosquitoes must out-compete native species to enable the resistance gene to become established. Advances in sequencing of vector and Plasmodium genomes will likely provide additional insights for the development of additional approaches to malaria control. [14]
Personal Protection Measures:
Personal protection measures such as the use of insect repellents such as DEET and wearing long trousers, long-sleeved shirts, and light-coloured clothes can reduce mosquito exposure. Repellents may be particularly effective in areas where malaria vectors feed outdoors or in the early evening when residents may not be using ITNs.
Education:
Participatory health education intervention contributes to the decreased malaria prevalence among children and increased the adult utilization of bednets with insecticide. Routine malaria education efforts may offer sustained benefits.
Vaccine:
Development of an effective malaria vaccine would be a major and important milestone in malaria control. Several approaches including subunit vaccines, whole irradiated sporozoite preparations, and transmission-blocking methods have been proposed. However, despite considerable hope, aggressive efforts, and substantial economic investment to develop an effective malaria vaccine, success has been elusive [15]. Most vaccine efficacy studies have demonstrated at best only modest protection from infection. In a recent pooled analysis of the results of phase 2 data for the most advanced candidate malaria vaccine (RTS,S/AS01 or AS02) Bejon and colleagues reported an overall vaccine efficacy of 36 per cent that was lowest, 4 per cent in high transmission areas. Moreover, no protection was observed after 3 years. A better understanding of the immunological mechanisms of malaria and second-generation vaccines may be needed before a vaccine can be effectively integrated into control efforts.
Treatment:
Treatment, which can serve to reduce the reservoir of people infected with malaria, and the period of infectivity, has already been addressed in this chapter. However it should be recognized that antimalarial therapy is not directly active against gametocytes.
[1] Centers for Disease Control and Prevention Anopheles Mosquitoes. (2012). [Online] Available at: http://www.cdc.gov/malaria/about/biology/ mosquitoes/index.html.
[2] Nájera JA, González-Silva M, Alonso PL. Some lessons for the future from the Global Malaria Eradication Programme (1955–1969). PLoS medicine. 2011 Jan 25;8(1):e1000412.
[3] Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD. Global malaria mortality between 1980 and 2010: a systematic analysis. The Lancet. 2012 Feb 4;379(9814):413-31.
[4] Lengeler, C. Insecticide-treated bed nets and curtains for pre- venting malaria. Cochrane Database of Systematic Reviews, 2, (2004). CD000363.
[5] Gamble CL, Ekwaru JP, ter Kuile FO. Insecticide‐treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews. 2006(2).CD003755.
[6] Pulford J, Hetzel MW, Bryant M, Siba PM, Mueller I. Reported reasons for not using a mosquito net when one is available: a review of the published literature. Malaria journal. 2011 Dec;10(1):1-0.
[7] Pluess B, Tanser FC, Lengeler C, Sharp BL. Indoor residual spraying for preventing malaria. Cochrane database of systematic reviews. 2010(4).
[8] Raghavendra K, Barik TK, Reddy BN, Sharma P, Dash AP. Malaria vector control: from past to future. Parasitology research. 2011 Apr;108(4):757-79.
[9] Keiser J, Singer BH, Utzinger J. Reducing the burden of malaria in different eco-epidemiological settings with environmental management: a systematic review. The Lancet infectious diseases. 2005 Nov 1;5(11):695-708.
[10] Centers for Disease Control and Prevention Human Factors and Malaria. (2010d). [Online] Available at: http://www.cdc.gov/malaria/about/ biology/human_factors.html.
[11] Bian G, Joshi D, Dong Y, Lu P, Zhou G, Pan X, Xu Y, Dimopoulos G, Xi Z. Wolbachia invades Anopheles stephensi populations and induces refractoriness to Plasmodium infection. Science. 2013 May 10;340(6133):748-51.
[12] Centers for Disease Control and Prevention. Anopheles Mosquitoes. (2012). [Online] Available at: http://www.cdc.gov/malaria/about/biology/ mosquitoes/index.html.
[13] Munhenga G, Brooke BD, Chirwa TF, Hunt RH, Coetzee M, Govender D, Koekemoer LL. Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa. Parasites & Vectors. 2011 Dec;4(1):1-1.
[14] Tymoshenko S, Oppenheim RD, Soldati-Favre D, Hatzimanikatis V. Functional genomics of Plasmodium falciparum using metabolic modelling and analysis. Briefings in functional genomics. 2013 Jul 1;12(4):316-27.
[15] Bejon P, White MT, Olotu A, Bojang K, Lusingu JP, Salim N, Otsyula NN, Agnandji ST, Asante KP, Owusu-Agyei S, Abdulla S. Efficacy of RTS, S malaria vaccines: individual-participant pooled analysis of phase 2 data. The Lancet infectious diseases. 2013 Apr 1;13(4):319-27.
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