Introduction
Malaria is a curable infectious disease caused by protozoan parasites called Plasmodium that infect the red blood cells. The parasites are transferred to humans by female anopheline mosquitoes. [1] The Plasmodium sporozoites, a life stage of the parasite, enter the human blood stream and invade the liver, where they multiply. While in the liver, another life stage of the parasite, merozoites, are released and invade the red blood cells. While in the red blood cells, the parasite continues to multiply, infecting and rupturing more red blood cells, clogging blood vessels, and causing symptoms, such as a high fever and damage to vital organs. Gametocytes, another life stage of the Plasmodium parasite, are released by the infected red blood cells and infect mosquitoes when they bite infected humans. The gametocytes develop into sporozoites while in the mosquito, which completes the Plasmodium’s life cycle. [2] In 1880, Charles Louis Alphonse Laveran, a French pathologist and parasitologist, was the first person to observe Plasmodium in human red blood cells. [3]
There are four Plasmodium species that infect humans: P. falciparum, P. vivax, P. malariae, and P. ovale. [4] The most common species are P. falciparum and P. vivax. P. falciparum causes the most deaths and is found in sub-Saharan Africa, Southeast Asia, the Western Pacific, and areas in the Amazon rainforest. P. vivax is commonly found in Asia, eastern Mediterranean, and parts of Central and South America. P. malariae and P. ovale are uncommon and cause a small percentage of infections. P. malariae is found in areas similar to P. falciparum. P. ovale is present in Africa, parts of Southeast Asia, and the Western Pacific. [5]
Malaria is most commonly found in the tropical climates of Africa, India, Southeast Asia, the Middle East, and Central and South America. [6] The majority of malaria cases and deaths occur in sub-Saharan Africa; however, in 2006 the disease was found in 109 countries and territories. [4] Individuals who have never been exposed to malaria and lack acquired immunity, such as young children (under 5 years old), pregnant women, and travelers from malaria-free regions, are most at risk for contracting the disease. Pregnant women lose their resistance to malaria and develop a high risk for infection. Once infected, the parasite develops in the placenta increasing the chance of low birth weight, and often death, in the newborn. Malaria infection also increases the risk for developing anemia, especially in children and pregnant women. Because malaria destroys red blood cells, it is difficult for anemic individuals to fight off the infection. [7] Individuals suffering from chronic anemia caused by malaria will often experience severe kidney and liver damage. [3] Once severe, malaria is usually fatal if untreated. [1]
In the middle of the nineteenth century, malaria affected approximately 90% of the world’s population. In 1945 the use of dichlorodiphenyltrichloroethane (DDT) to control malaria began. In 1955 the 8th World Health Assembly began the Global Malaria Eradication campaign in all malaria-endemic countries except for Madagascar and the countries within the sub-Saharan Africa region. This campaign focused on vector control with indoor residual spraying (IRS) with DDT along with case management. In 1950, 143 countries were malaria endemic. After the implementation of the Global Malaria Eradication campaign, 37 of the 143 endemic countries were malaria-free by 1978. Twenty-seven of those malaria-free countries were in the Americas and in Europe. Even though the eradication campaign was successful in many of the malaria-endemic countries, some countries were still unable to combat malaria transmission. In these regions, the campaign changed from eradication to control efforts and the eradication campaign ended. After the eradication campaign ended, some countries completely eradicated malaria including Tunisia in 1979, Maldives in 1984, and the United Arab Emirates in 2007. [5] International attention on malaria substantially decreased after the abandoned Global Malaria Eradication campaign of the 1950s to 1970s. However, the past decade has seen an increase in awareness of malaria.
- In 1998, The Roll Back Malaria (RBM) Partnership was created by the World Health Organization, the United Nations Children’s Fund, the United Nations Development Programme, and the World Bank as a global coordinating organization to eradicate malaria. RBM is now comprised of hundreds of people including all of the malaria-endemic countries, nongovernmental organizations, universities, foundations, donor countries, and private individuals. One of the main goals of RBM is “halving global malaria infections by 2010” and reducing malaria deaths by 70% (of the 2000 levels) by 2015. [8]
- The Global Malaria Action Plan (GMAP) was created by the RBM to “foster agreement among all partners around the goals, strategy, and activities that the RBM Partnership will pursue, and to clearly lay out those goals, strategies, and activities.” [5]
- African leaders committed to cut malaria mortality by half by 2010 in the Abuja Declaration of 2000.
- The United Nations’ Millennium Development Goals include stopping and “reversing” the incidence of malaria by 2015. [5]
- The Asia Pacific Malaria Elimination Network held its first meeting in Brisbane, Australia on February 9, 2009. The Network consists of 10 countries in the Asia-Pacific region including: Bhutan, China, Indonesia, Malaysia, North Korea, the Philippines, the Solomon Islands, South Korea, Sri Lanka, and Vanuatu. The purpose of the network is to coordinate efforts, share information, and form a collective advocacy group. All countries were represented at the meeting, expect for Bhutan and North Korea. [9]
- In 2004, The Pan American Health Organization (PAHO) began a program to fight malaria in the Mesoamerican region without the use of toxic insecticides, such as DDT, which is an effective but highly toxic insecticide. Eight countries in the region (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama) are cooperating with the PAHO and the Global Environment Facility (GEF) is also supporting the program. This anti-malaria program includes four main components: (1) creating “demonstration projects” that teach alternative ways to control malaria, (2) increasing countries’ “institutional capacity” to combat malaria, (3) eliminating all “persistent organic pollutants,” such as DDT, and (4) creating a strong and coordinated management structure. This PAHO collaborative program has been successful, with the number of malaria cases dropping by 60% from 2004 to 2007 in areas where the program has been implemented. [3]
Malaria disproportionately affects the poor and contributes to the cycle of poverty. The disease creates an economic burden on endemic countries. In countries with high transmission rates, the Gross Domestic Product (GDP) has decreased by approximately 1.3% per year. Over time, as little as a decade, that decrease can result in billions of dollars lost in GDP. In Africa, malaria costs approximately $12 billion in direct losses, such as illness, treatment and premature death. [5]
Statistic
- In 2006, there were approximately 247 million cases of malaria worldwide. Eighty-six percent of the cases were in the African region. Eighty percent of the African cases occurred in 13 different countries, with more than half occurring in Nigeria, Democratic Republic of the Congo, Ethiopia, United Republic of Tanzania, and Kenya. Of the episodes of malaria that occurred outside the African region, 80% occurred in India, Sudan, Myanmar, Bangladesh, Indonesia, Papua New Guinea, and Pakistan. [10]
- There are 109 countries affected by malaria. In the Asia-Pacific region, there are 20 countries or territories with malaria present: South Asia (5), Eastern Asia (3), Southeast Asia (9), and Western Pacific (3).
- In 2006, there were an estimated 881,000 deaths caused by malaria, with 91% of those deaths occurring in Africa and 85% of those deaths were children aged 5 years and younger.
- In 2006, approximately 3.3 billion people were at risk for contracting malaria. Out of the total at-risk cases, 2.1 billion were at low risk (i.e. less than 1 reported case per 1000 population) and 97% of those people were living in areas other than Africa. There were 1.2 billion people at a high risk for malaria infection (ie, greater than 1 case per 1000 population), 49% of these people were living in the African region and 37% were living in Southeast Asia.
- In the Asia-Pacific region there are more than 2.2 billion people at risk of malaria, which represents 67% of the world’s at-risk population.
- There are 92 malaria-free countries and territories worldwide. [5] [10]
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
The first symptoms of malaria are similar to any viral illness including: fever, headache, chills, fatigue, body aches, perspiration, and vomiting. These symptoms typically occur within 10 to 15 days following infection. [4] Symptoms of severe Falciparum malaria include impaired consciousness, respiratory distress, convulsions, circulatory collapse, pulmonary oedema, abnormal bleeding, jaundice, and haemoglobinuria.[10]
Treatment Options
Conventional
Uncomplicated malaria is the symptomatic infection of malaria without signs of severity and/or evidence of vital organ dysfunction. Severe falciparum malaria is defined as “acute falciparum malaria with signs of severity and/or evidence of vital organ dysfunction.” The goal of treating uncomplicated malaria is to cure the infection. As for severe malaria, the goal of treating is to prevent death. [1]
The WHO recommends treating malaria within 24 hours of symptom onset. A combination of drugs called, Artemisinin-based combination therapies (ACT), are currently the best treatment for malaria, particularly for “uncomplicated falciparum malaria;” however, there is increasing potential for parasite resistance to these drugs. Annual procurement of ACT increased from 4 million doses in 2004 to nearly 100 million doses in 2006, 69 million were in Africa. Between 2006 to 2007, ACT coverage was low in Africa because of limited accessibility and high costs in rural areas. Only 3% of children under the 5 years of age were given ACT. Currently, there are no alternatives to ACT and no drugs nearing completion in the development process. The WHO recommends preventative measures to aid in malaria eradication: [4] [5]
- Long-lasting insecticidal nets (LLIN): LLIN, also known as insecticide–treated bed nets (ITN), are placed over the beds of individuals while sleeping. Annual production ITN increased from 30 million in 2004 to 95 million in 2007. There has been a significant increase in funding for insecticidal nets, which has led to an increase of procurement and distribution from 1.3 million nets in 2004 to 30 million nets in the first 6 months of 2007. UNICEF increased its net procurement from 7 million in 2004 to 25 million in 2006.
- Intermittent preventative treatment for pregnant women (IPTp): The WHO recommends treating pregnant women with at least two doses of sulphadoxine-pyrimethamine when fetal motion first occurs or in the second and third trimesters. IPT clears the placenta of parasites. This recommendation is for pregnant women in high-transmission areas in Africa. All 35 sub-Saharan African countries where IPTp use is recommended have adopted IPTp use as an official policy. Implementation had begun in all of these countries by the end of year 2007, but only 20 of these countries had fully integrated the policy nationally.
- Indoor residual spraying (IRS): IRS is the process of spraying insecticides on the inside walls of homes. IRS is most commonly used in endemic regions outside of Africa, such as Southeast Asia. DDT and pyrethroids are the most common insecticides used. In 2006, approximately 24 million households worldwide utilized IRS. IRA use is inhibited by funding limitation and logistical and implementation problems. [5]
Malaria infection requires prompt evaluation and treatment. In most cases, conventional treatment consists of administering either one or a combination of the following medications:
- chloroquine
- hydroxychloroquine
- quinine sulfate
- sulfadoxine and pyrimethamine
- mefloquine
- proguanil
- atovaquone
- doxycycline
- primaquine
Anti-malarial drugs have numerous side effects and must be prescribed based on specific individual, their geographic location, severity of their infection and their age at onset. Drug resistance is a dominant issue in malaria treatment and is the drive focus for new drug investigations.
Nutritional Supplementation
Vitamin A
Multiple studies have indicated a link between vitamin A deficiency and malaria, including the mortality from malaria in children. [11] While it remains unclear as to which comes first (the deficiency or the disease), vitamin A supplementation is one of the methods being reviewed as a potential preventative measure that can be taken along with the proper use of netting and other standard procedures. [12][13] Regardless of the initiating incident, vitamin A deficiency in children with malaria causes increased rates of mortality and long-term consequences. Supplementation with vitamin A may reduce mortality rates especially when provided during infancy stage. [14] In addition, it has been demonstrated that supplementation with iron and vitamin A may decrease the incidence of malarial attack. [15] These findings contradict earlier reports that vitamin A supplementation did not demonstrate significant improvements either in reduction of onset events or mortality. [16] These contradictory findings do not disregard the relationship between vitamin A deficiency and malaria; however, a recent review study has established that the parameters of clinical studies needed to be standardized in order to have a more indisputable data. [12]
Zinc
Zinc deficiency is associated with lowered immunity. [17] In addition to research on Vitamin A, studies have indicated potentially positive outcomes in malarial infections when supplementation with zinc is implemented primarily due to an overall improvement in nutritional status. [14][18] These findings have led to recommendations of zinc supplementation in conjunction with other primary micro-nutrients as a preventative measure against onset of malaria with some recommendations that zinc supplementation may reduce the duration of infection. [13][14] However, more recent reviews of the available literature have found insufficient evidence to support these claims. Further clarification is needed to confirm the role of zinc and its relationship to malaria. [19][20]
Iron
Anemia is common in areas where malaria is prevalent and is often fatal for those suffering from the infection. [21] Again, as overall nutrient status is related to infection, duration and mortality, micronutrient supplementation with iron as well as ainc and vitamin A is recommended to improve overall nutritional status thereby improving possible outcomes. [14][22] Malarial hemolysis has also been found to be responsible for increased anemia. [23] However, there is evidence that iron supplementation aggravates some of the malariometric markers due to the necessity of iron in the parasites proliferation. [24] Regardless of these findings, restriction of iron has not been recommended. [15]
B Vitamins
General malnutrition is recorded in the majority of malarial infections. This is possibly due to the findings that the malaria parasite metabolizes nutrients from the beginning (de novo), and it has been found that B vitamins are procured by the parasite thereby reducing overall nutritional status. [25]
Herbal Supplementation
General
All regions that have a high incidence of malaria also have a long history of treating the disease with medicinal botanicals and other traditional medicines. With the exception of extracts from the Artemisia plant, there is limited scientific evidence to support many of the herbs used. Additionally, herbs grown in one region may act differently than those grown in other regions thereby making consistent testing difficult. While by no means a complete list of all traditional herbs used to treat malaria, the list below recognizes those that have the most consistent use within the countries surveyed:
India – Andrographis paniculata (Brum. f.) Wall. ex Nees.; (Kalmegh); Bacopa monnieri Linn. (penn.); Scrophulariaceae (Brahmi); Caesalpinia boducella, Flem.; Caesalpiniaceae (Gatayan); Diplocyclos palmatus (L.) Jeffrey.; Eclipta prostata Roxb. (Bhringraj); Fumaria indica H. (Pitpapar); Leucas aspera (Willd.) L. (Gumma); Mimosa pudica L. (Lajawanti); Nyctanthes arbor-tristis L. (Harsingar); Ocimum sanctum L. (Tulsi); Plumbago zeylanica L. (Chitrak); Tinospora cordifolia (Willd.) Miers. (Giloya); Zingiber officinale, Rosc. (Adarakh). [26]
Brazil – Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens, Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, Coutarea hexandra. [27]
Uganda – Aristolochia elegans, (kapapula or ‘little paper’), Vernonia amygdalina, (mululuza), and Artemesia annua. [28]
Andrographis paniculata (Kalmegh)
A. paniculata has a history of traditional use in treating malaria and preliminary studies have indicated that it may possess anti-malarial properties. [29]
Azadirachta indica (Mahanimba)
The leaves of A. indica contain the lemonoid gedunum which has demonstrated activity against two clones of Plasmodium falciparum and in laboratory analysis appeared to be as effective as chloroquine. [30] In addition to viewing the properties of A. indica as candidates for treating malaria, the oil from this plant has been shown to have insecticidal and insect repellant properties. [31][32][33][34][35] A. indica extract appears to have demonstrated similar properties to the oil as a topical repellant. [36] Some laboratory analyses have also been conducted on the insect repellant properties of the fruit. [37]
Cymbopogon citratus Stapf. Essential Oil (Lemongrass)
An in vivo test examined lemongrass and basil essential oils and their possible anti-malarial activity. Both oils showed promising activity in mice over a four-day period of treatment; however, lemongrass oil showed stronger anti-malarial activity against this specific parasite. [38]
In an effort to identify a cost effective addition to the use of netting in the Amazon region’s malaria vector, researchers examined the repellency of lemongrass essential oil applied topically with results demonstrating a 74% protective effect for 2.5 hours. [39]
Artemisia afra (African Wormwood)
Artemisia afra (dried arial parts) was found to have weak antimalarial activity against Plasmodium falciparum of petrol ether and dichloromethane extracts but no activity of methanolic extracts (hypoxanthine uptake assay). [40] It is also used to promote appetite. [41]
Clinical Notes
Before treatment begins, parasitological diagnosis is recommended, except for children under the age of 5 who live in high-risk areas. There are two methods used for the diagnosis of malaria: light microscopy and rapid diagnostic tests (RDT). The advantage of light microscopy is low cost with high sensitivity and specificity. RDT are used for parasite antigen detection which are more expensive than light microscopy. RDT have variable sensitivity and specificity and they are sensitive to humidity and high temperatures, however, RDT make wide-spread diagnosis possible. RDT does not require professional training and can be used in the home, community, and by local health care providers. Light microscopy does not have that capability. In 2006, approximately 152 million clinically confirmed cases of malaria occurred, predominantly by microscopy. RDT production increased from 2.9 million in 2000 to approximately 80 to 90 million in 2008. In 2006, 15.6 million RDT were distributed. RDT use is inhibited by funding, training, and concerns of quality. [1][5]
References
- World Health Organization. WHO guidelines for the treatment of malaria. Geneva (Switzerland): WHO Press; 2006.
- S.I. Hay. A world malaria map: Plasmodium falciparum endemicity in 2007. PLoS Med. 2009; 6(3):286-302.
- C. Chelala. Taking a bite out of malaria. Américas. Sep/Oct2008;60(5):38-45.
- World Health Organization. Malaria fact sheet. Available from http://www.who.int/mediacentre/factsheet/fs094/en/print/html. [Accessed on 29 July 2009].
- Roll Back Malaria. Global malaria action plan. Available from http://www.rollbackmalaria.org/gmap/toc.html. [Accessed on 29 July 2009].
- C.A. Turkington, K.R. Wells. Malaria. In: Longe JL, editor. Gale Encyclopedia of Medicine. 3rd edition. Detroit: Gale online update. 2007. p.518
- United States Centers for Disease Control and Prevention. Global malaria prevention and control program: moving ahead in the 21st century. Available from http://www.cdc.gov/malaria/pdf/globalmalaria.pdf. [Accessed on 29 July 2009].
- Hope and fears for malaria. Bulletin of the World Health Organization. February2008;86(2):91-92.
- Global Health Report. Malaria: delegates from Asia-Pacific countries meet in Australia to discuss malaria eradication. 9 February 2009. Available from http://www.globalhealthreporting.org/article_printable.asp?DR_ID=56862. [Accessed on 29 July 2009].
- World Health Organization. World malaria report 2008. Geneva (Switzerland): WHO Press. 2008.
- M.A. Sanjoaquin, M.E. Molyneux. Malaria and vitamin A deficiency in African children: a vicious circle? Malar J. 17Jun2009;8:134.
- V.S. Moorthy, Z. Reed, P.G. Smith. Clinical trials to estimate the efficacy of preventive interventions against malaria in paediatric populations: a methodological review. Malar J. 10Feb2009;8:23.
- Z.A. Bhutta, T. Ahmed, R.E. Black, S. Cousens, K. Dewey, E. Giugliani, B.A. Haider, B. Kirkwood, S.S. Morris, H.P. Sachdev, M. Shekar. What works? Interventions for maternal and child undernutrition and survival. Lancet. 2Feb2008;371(9610):417-440.
- V.J. Temple, A. Masta. Zinc in human health. P N G Med J. Sep-Dec2004;47(3-4):146-158.
- A.H. Shankar. Nutritional modulation of malaria morbidity and mortality. J Infect Dis. Sep2000;182(Suppl 1):S37-53.
- U. Ramakrishnan, R. Martorell. The role of vitamin A in reducing child mortality and morbidity and improving growth. Salud Publica Mex. Mar-Apr1998;40(2):189-198.
- R.E. Black. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr. May2003;133(5 Suppl 1):1485S-1489S.
- L.E. Cuevas, A. Koyanagi. Zinc and infection: a review. Trop Paediatr. Sep2005;25(3):149-160.
- B.A. Haider, Z.A. Bhutta. The effect of therapeutic zinc supplementation among young children with selected infections: a review of the evidence. Food Nutr Bull. Mar2009;30(1 Suppl):S41-S59.
- S. Overbeck, L. Rink, H. Haase. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp (Warsz). Jan-Feb2008;56(1):15-30.
- V. Nussenblatt, R.D. Semba. Micronutrient malnutrition and the pathogenesis of malarial anemia. Acta Trop. Jun2002;82(3):321-337.
- L.E. Caulfield, S.A. Richard, R.E. Black. Undernutrition as an underlying cause of malaria morbidity and mortality in children less than five years old. Am. J. Trop. Med. Hyg. 2004;71(2 suppl):55-63.
- B.J. Brabin, P.D. Prinsen-Geerligs, F.H. Verhoeff, K.A. Fletcher, L.H. Chimsuku, B.M. Ngwira, O.J. Leich, R.L. Broadhead. Haematological profiles of the people of rural southern Malawi: an overview. Ann Trop Med Parasitol. Jan2004;98(1):71-83.
- N.S. Postma, E.C. Mommers, W.M. Eling, J. Zuidema. Oxidative stress in malaria; implications for prevention and therapy. Pharm World Sci. Aug1996;18(4):121-129.
- S. Müller, B. Kappes. Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites. Trends Parasitol. Mar2007;23(3):112-121.
- A. Dwivedi, R. Patel, D. Jhade, R. Sachan, A. Argal. Traditional Phytotherapy used in the Treatment of Malaria by Rural People of Bhopal, District of Madhya Pradesh, India. Ethnobotanical Leaflets. 2009;13: 475-479.
- S.B. Alexandros. Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal. J Ethnobiol Ethnomedicine. 2007;3:18.
- P. Wamboga-Mugirya. Uganda tests its traditional anti-malaria ‘drugs’. Science and Development Network. Jan.2005. Available from http://www.scidev.net/en/health/features/uganda-tests-its-traditional-antimalaria-drugs.html. [Accessed on 31 August 2009].
- V.K. Dua, V.P. Ojha, R. Roy, B.C. Joshi, N. Valecha, C.U. Devi, M.C. Bhatnagar, V.P. Sharma, S.K. Subbarao. Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata. J Ethnopharmacol. Dec2004;95(2-3):247-251.
- S. MacKinnon, T. Durst , J.T. Arnason, C. Angerhofer, J. Pezzuto, P.E. Sanchez-Vindas, L.J. Poveda, M. Gbeassor. Antimalarial activity of tropical Meliaceae extracts and gedunin derivatives. J Nat Prod. Apr1997;60(4):336-341.
- H. Vatandoost, V.M. Vaziri. Larvicidal activity of a neem tree extract (Neemarin) against mosquito larvae in the Islamic Republic of Iran. East Mediterr Health J. Jul-Sep2004;10(4-5):573-581.
- R. Dhar, K. Zhang, G.P. Talwar, S. Garg, N. Kumar. Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions. J Ethnopharmacol. May1998;61(1):31-39.
- A.K. Mishra, N. Singh, V.P. Sharma. Use of neem oil as a mosquito repellent in tribal villages of mandla district, madhya pradesh. Indian J Malariol. Sep1995;32(3):99-103.
- V.P. Sharma, M.A. Ansari, R.K. Razdan. Mosquito repellent action of neem (Azadirachta indica) oil. J Am Mosq Control Assoc. Sep1993;9(3):359-360.
- F.O. Okumu, B.G. Knols, U. Fillinger. Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria vector Anopheles gambiae. Malar J. 22May2007;6:63.
- I.W. Jones, A.A. Denholm, S.V. Ley, H. Lovell, A. Wood, R.E. Sinden. Sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues. FEMS Microbiol Lett. 15Jul1994;120(3):267-273.
- C. Coria, W. Almiron, G. Valladares, C. Carpinella, F. Ludueña, M. Defago, S. Palacios. Larvicide and oviposition deterrent effects of fruit and leaf extracts from Melia azedarach L. on Aedes aegypti (L.) (Diptera: Culicidae). Bioresour Technol. May2008;99(8):3066-3070.
- F. Tchoumbougnang. In vivo antimalarial activity of essential oils from Cymbopogon citratus and Ocimum gratissimum on mice infected with Plasmodium berghei. Planta Med. Jan2005;71(1):20-23.
- S.J. Moore. Field evaluation of traditionally used plant-based insect repellents and fumigants against the malaria vector Anopheles darlingi in Riberalta, Bolivian Amazon. J Med Entomol. Jul2007;44(4):624-630.
- H. Weenen. Antimalarial activity of Tanzanian medicinal plants. Planta Medica. 1990;56(4):368-370.
- M. RobertsM. Margaret Roberts’ A-Z of Herbs. Cape Town, South Africa; Struik Publishers; 2003. p68
