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1.  Medicinal Plants Used for Treatment of Diabetes by the Marakh Sect of the Garo Tribe Living in Mymensingh District, Bangladesh 
Diabetes mellitus is an endocrinological disorder arising from insulin deficiency or due to ineffectiveness of the insulin produced by the body. This results in high blood glucose and with time, to neurological, cardiovascular, retinal and renal complications. It is a debilitating disease and affects the population of every country of the world. Around 200 million people of the world suffer from this disease and this figure is projected to rise to 300 million in the coming years. The disease cannot be cured with allopathic medicine as the drugs used do not restore normal glucose homeostasis and moreover have side-effects. On the other hand, traditional medicinal practitioners of various countries claim to cure diabetes or at least alleviate the major symptoms and progression of this disease through administration of medicinal plants. The Garos are an indigenous community of Bangladesh, who still follow their traditional medicinal practices. Their traditional medicinal formulations contain a number of plants, which they claim to be active antidiabetic agents. Since observation of indigenous practices have led to discovery of many modern drugs, it was the objective of the present study to conduct a survey among the Marakh sect of the Garos residing in Mymensingh district of Bangladesh to find out the medicinal plants that they use for treatment of diabetes. It was found that the tribal practitioners of the Marakh sect of the Garos use twelve medicinal plants for treatment of diabetes. These plants were Lannea coromandelica, Alstonia scholaris, Catharanthus roseus, Enhydra fluctuans, Terminalia chebula, Coccinia grandis, Momordica charantia, Cuscuta reflexa, Phyllanthus emblica, Syzygium aqueum, Drynaria quercifolia, and Clerodendrum viscosum. A review of the scientific literature demonstrated that almost all the plants used by the Garo tribal practitioners have reported antidiabetic and/or antioxidant properties and have enormous potential for possible development of new and efficacious antidiabetic drugs.
PMCID: PMC3746667  PMID: 23983370
Diabetes; CAM; ethnomedicine; Garo
2.  Survey and Scientific Evaluation of Medicinal Plants Used by the Pahan and Teli Tribal Communities of Natore District, Bangladesh 
The Pahans and the Telis are two of the smallest indigenous communities in Bangladesh. The Pahans, numbering about 14,000 people are widely scattered in several northern districts of the country, while the Telis are such a small community that nothing has been reported on their numbers and lifestyle. Both tribes are on the verge of disappearance. One each of the Pahan and the Teli community was located after much search in two adjoining villages of Natore district, Bangladesh. Since the tribes were found to still depend on their traditional medicinal practitioners for treatment of ailments, it was the objective of the present study to document their traditional usage of medicinal plants and to evaluate such plants against modern research-based pharmacological activity studies on these plants. Interviews were conducted of the practitioners of the Pahan and Teli community of Natore district with the help of a semi-structured questionnaire and using the guided field-walk method. Plant specimens as pointed out by the practitioners were collected and pressed on the field and identification completed at the Bangladesh National Herbarium. The Pahan tribal practitioners used 13 plants distributed into 9 families for treatment of 14 different ailments. The Teli tribal practitioner used 15 plants divided into 14 families for treatment of 17 different ailments. Eight out of the thirteen plants used by the Pahan tribal practitioner (61.5%) had reported relevant pharmacological activities in the scientific literature, while six out of the fifteen plants used by the Teli tribal practitioners (40%) had such relevant pharmacological activities in accordance with their usage. The medicinal plants used by the Pahans and Telis warrant further scientific studies toward discovery of lead compounds and efficacious drugs and the documentation and protection of the traditional medical knowledge held by these tribes.
PMCID: PMC3746669  PMID: 23983368
Asian medicine; CAM; ethnomedicine; alternative therapy
3.  Medicinal Formulations of a Kanda Tribal Healer — A Tribe on the Verge of Disappearance in Bangladesh 
The Kanda tribe is one of the lesser known small tribes of Bangladesh with an estimated population of about 1700 people (according to them), and on the verge of extinction as a separate entity. To some extent, they have assimilated with the surrounding mainstream Bengali-speaking population, but they still maintain their cultural practices including traditional medicinal practices, for which they have their own tribal healers. Nothing at all has been documented thus far about their traditional medicinal practices and formulations, which are on the verge of disappearance. The Kanda tribe can be found only in scattered tea gardens of Sreemangal in Sylhet district of Bangladesh; dispersion of the tribe into small separated communities is also contributing to the fast losing of traditional medicinal practices. The objective of the present study was to conduct an ethnomedicinal survey among the traditional healers of the Kanda tribe (in fact, only one such healer was found after extensive searches). Information was collected from the healer with the help of a semi-structured questionnaire and the guided field-walk method. A total of 24 formulations were obtained from the healer containing 34 plants including two plants, which could not be identified. Besides medicinal plants, the Kanda healer also used the body hairs of the Asiatic black bear (Ursus thibetanus) and bats (Pteropus giganteus giganteus) in one of his formulation for treatment of fever with shivering. The ailments treated by the Kanda healer were fairly common ailments like cuts and wounds, skin diseases, helminthiasis, fever, respiratory problems (coughs, asthma), gastrointestinal disorders (stomach pain, constipation, diarrhea), burning sensations during urination, various types of pain (headache, body ache, toothache, ear ache), conjunctivitis, poisonous snake, insect or reptile bites, jaundice, and bone fractures. A number of important drugs in allopathic medicine like quinine, artemisinin, and morphine (to name only a few) have been discovered from observing indigenous medicinal practices. From that view point, the formulations used by the Kanda healer merit scientific studies for their potential in the discovery of cheap and effective new drugs. Scientific validation of the medicinal formulations of the Kanda healer can also be effective for treatment of ailments among this tribe, which does not have or does not want to have any contact with modern medicine.
PMCID: PMC3746568  PMID: 24146444
4.  A survey of medicinal plants used by the Deb barma clan of the Tripura tribe of Moulvibazar district, Bangladesh 
Background
The number of tribes present within Bangladesh has been estimated to approximate one hundred and fifty. Information on traditional medicinal practices, particularly of the smaller tribes and their clans is lacking. It was the objective of the study to document the tribal medicinal practices of the Deb barma clan of the Tripura tribe, which clan can be found residing in Dolusora Tripura Palli of Moulvibazar district of Bangladesh. A further objective was to determine the extent of the community households who still prefer traditional treatment to other forms of treatment, particularly allopathic treatment.
Methods
Interviews of the tribal healer and the tribal community regarding their ethnomedicinal practices were carried out with the help of a semi-structured questionnaire and the guided field-walk method. All together 67 clan members were interviewed including the Headman, tribal healer, 19 Heads of households and 46 other adult members of the clan. Information on number of members of household, their age, gender, educational status, occupation of working household members and preferred mode of treatment was obtained through the semi-structured questionnaire. In the guided field-walk method, the healer took the interviewers on field-walks through areas from where he collected his medicinal plants, pointed out the plants, and described their uses.
Results
The clan had a total of 135 people distributed into 20 households and had only one traditional healer. Use of medicinal plants, wearing of amulets, and worship of the evil god ‘Bura debta’ constituted the traditional medicinal practices of the clan for treatment of diseases. The healer used a total of 44 medicinal plants distributed into 34 families for treatment of various ailments like pain, coughs, cold, gastrointestinal disorders, cuts and wounds, diabetes, malaria, heart disorders, and paralysis.
Conclusions
Available scientific reports validate the use of a number of plants by the traditional healer. A number of the plants used by the clan healer had reported similar uses in Ayurveda, but differ considerably in their therapeutic uses from that reported for other tribes in Bangladesh. The present survey also indicated that in recent years the Deb barma clan members are inclining more towards allopathic medicine.
doi:10.1186/1746-4269-10-19
PMCID: PMC3996145  PMID: 24502444
Indigenous knowledge; Allopathic medicine; Ethnomedicine; Bangladesh
5.  Tribal Formulations for Treatment of Pain: A Study of the Bede Community Traditional Medicinal Practitioners of Porabari Village in Dhaka District, Bangladesh 
The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long. As a result of their strenuous lifestyle, they suffer from various types of pain, and have developed an assortment of formulations for treatment of pain in different parts of the body. Pain is the most common reason for physician consultation in all parts of the world including Bangladesh. Although a number of drugs are available to treat pain, including non-steroidal, steroidal, and narcotic drugs, such drugs usually have side-effects like causing bleeding in the stomach over prolonged use (as in the case of rheumatic pain), or can be addictive. Moreover, pain arising from causes like rheumatism has no proper treatment in allopathic medicine. It was the objective of the present study to document the formulations used by the Bede traditional practitioners for pain treatment, for they claim to have used these formulations over centuries with success. Surveys were conducted among a large Bede community, who reside in boats on the Bangshi River by Porabari village of Savar area in Dhaka district of Bangladesh. Interviews of 30 traditional practitioners were conducted with the help of a semi-structured questionnaire and the guided field-walk method. It was observed that the Bede practitioners used 53 formulations for treatment of various types of pain, the main ingredient of all formulations being medicinal plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain, either exclusively, or along with other types of body pain. A total of 65 plants belonging to 39 families were used in the formulations. The Fabaceae family provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the 53 formulations were used topically, 5 formulations were orally administered, and 1 formulation had both topical and oral uses. 8 formulations for treatment of rheumatic pain contained Calotropis gigantea, suggesting that the plant has strong potential for further scientific studies leading to discovery of novel efficacious compounds for rheumatic pain treatment.
PMCID: PMC3746354  PMID: 24082322
6.  Ethnomedicinal plants used by the Nag clan of the Rai Ghatual tribe of Moulvibazar district, Bangladesh 
Ancient Science of Life  2013;32(4):217-221.
Context:
Medicinal practices of the tribes of Bangladesh remain largely un-documented.
Aims:
The aim of the present study was to conduct an ethnomedicinal survey and documentation among the Nag clan of the Rai Ghatual tribe of Bangladesh.
Settings and Design:
The survey was carried out among the Nag clan of the Rai Ghatual tribal community of Moulvibazar district. The clan, according to them, is the only Nag clan of the Rai Ghatual tribe in Bangladesh. The clan has three tribal healers, still continuing their traditional medicinal practices.
Materials and Methods:
Interviews of the healers were carried out with the help of a semi-structured questionnaire and the guided field-walk method.
Results:
The Nag clan healers were observed to use 28 different plant species distributed into 22 families for treatment of ailments such as fever, loss of appetite, male infertility, dysentery, lower abdominal pain during menstruation, jaundice, stomachache, burning sensations during urination, bodily pain and weak health.
Conclusions:
This is the first reported study of the traditional medicinal practices of Nag clan healers. Several of the plants can be validated in their uses on the basis of existing scientific literature. The medicinal plants used by the Nag healers warrant further scientific studies, for the plants are readily available and can form alternative medicinal sources instead of costlier biomedical drugs.
doi:10.4103/0257-7941.131975
PMCID: PMC4078472  PMID: 24991070
Bangladesh; ethnomedicine; Moulvibazar; Nag clan; Rai Ghatual
7.  A Plant-Derived Morphinan as a Novel Lead Compound Active against Malaria Liver Stages  
PLoS Medicine  2006;3(12):e513.
Background
The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s.
Methods and Findings
Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 μM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 μM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 μM, TI 46, and IC50 42.4 μM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages.
Conclusions
A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs.
A derivative of a morphinan alkaloid, tazopsine, from a plant used against malaria in Madagascar, is active against the hepatic stages ofPlasmodium species.
Editors' Summary
Background.
The parasite that causes malaria has quickly developed resistance to many of the drugs that are commonly used to treat this disease. As a result, new drugs and drug combinations are needed. In some parts of the world where antimalarial drugs are failing due to resistance, or are not available to everyone, people often turn to traditional herbal remedies instead. These traditional plant remedies can be a useful starting point for development of new drugs, but the process of developing effective new drugs from plant remedies is long and complicated. An important initial step is to isolate and identify the active compounds from plants and then see how well these compounds perform against malaria parasites in laboratory tests. If the tests are successful, such compounds could then progress to experiments in animals and possibly eventually human trials. One plant used widely in Madagascar for treatment of malaria is Strychnopsis thouarsii; the traditional remedy consists of the plant stem bark boiled in water.
Why Was This Study Done?
The group of researchers doing this study wanted to discover candidates for new malaria drugs. They therefore wanted to find out which molecular compounds in the stem bark of S. thouarsii contained antimalarial activity, and what particular stage of the malaria parasite's life cycle these compounds had an effect on. The researchers suspected that the agents in this plant bark had some activity against the “liver stage” of malaria infection in humans. This is the first stage of infection, after a person has been bitten by a malaria-infected mosquito, and before blood cells are invaded by malaria parasites (which then causes the disease symptoms). Very few drugs currently in existence have an effect on the “liver stage” of infection, but activity at this stage would be tremendously useful because it could mean a drug is better for prevention of malaria than others in existence.
What Did the Researchers Do and Find?
First, the researchers wanted to take the traditional herbal remedy—of S. thouarsii bark boiled in water—and find out precisely which molecule in that remedy was responsible for the antimalarial activity. They therefore used a method called chromatography to progressively separate the herbal extract into its distinct components. At each stage of separation, the extract was checked for activity against malaria using a laboratory test. Inactive extracts were disregarded, and the active component then taken on to a further separation round. After many rounds of separation and testing, the researchers got down to a single, apparently new, molecule that was active against malaria in the laboratory test, and this molecule was named tazopsine (in the Malagasy language the word Tazo refers to malaria). In order to find out how effective the molecule was at killing malaria parasites, the researchers took human or mouse liver cells cultured in the laboratory, infected them with malaria parasites (either the malaria parasite that normally infects humans, or a related species that infects mice), and then added tazopsine at different concentrations. The compound completely killed the malaria parasites even at very low concentrations, and had activity against malaria infecting either liver cells or red blood cells. Tazopsine was then given to mice injected with a species of the malaria parasite. The compound protected most mice against malaria infection when it was used at a dosage level lower than the toxic dose. The researchers then tried making a series of different variants of tazopsine in the hope that some variants would be less toxic, but equally active as, the original compound. They found one variant, named NCP-tazopsine, that was much less toxic but just as active as tazopsine, but only against the malaria infecting liver cells.
What Do These Findings Mean?
In these experiments a new molecule, tazopsine, was discovered from a Malagasy plant, and it was found to be active against liver-stage malaria parasites, in laboratory experiments and in mice. This molecule or variants of it could in future become candidate antimalarial drugs in humans. However, much work would need to be done before testing could get to that stage. Different variants of molecules related to tazopsine would need to be tested to find one that has low toxicity, and these variants would need to be fully evaluated in animals to see how they are handled in the body before any trials could begin in humans.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030513
The World Health Organization publishes a minisite containing links to information about all aspects of malaria worldwide, including treatment, prevention, and current programmes for malaria control
Medicines for Malaria Venture is a collaboration between public and private organizations (including the pharmaceutical industry) that aims to fund and manage the development of new drugs for treatment and prevention of malaria
Wikipedia entries for drug discovery and drug development (note: Wikipedia is an internet encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030513
PMCID: PMC1716192  PMID: 17194195
8.  Medicinal Plants Used by the Mandais - A Little Known Tribe of Bangladesh 
The Mandais are a little known tribe of Bangladesh inhabiting the north central regions, particularly Tangail district of Bangladesh. Their population has been estimated to be less than 10,000 people. Although the tribe has for the most part assimilated with the mainstream Bengali-speaking population, they to some extent still retain their original tribal customs, including their traditional medicinal practices. Since this practice is also on the verge of disappearance, the objective of the present study was to conduct an ethnomedicinal survey among Mandai tribal practitioners to document their use of medicinal plants for treatment of various ailments. Four traditional practitioners were found in the exclusive Mandai-inhabited village of Chokchokia in Tangail district. Information was collected from the practitioners with the help of a semi-structured questionnaire and guided field-walk method. It was observed that the four traditional practitioners used a total of 31 plants distributed into 23 families for treatment. The various ailments treated included diabetes, low semen density, jaundice, gastrointestinal tract disorders (stomach ache, indigestion, dysentery, and diarrhea), leucorrhea, pain (rheumatic pain, joint pain), skin disorders, respiratory tract disorders (coughs, mucus, and allergy), debility, fever, and helminthiasis. From the number of plants used (seven), it appeared that gastrointestinal tract disorders formed the most common ailment among the Mandai community, possibly brought about by the low income status of the people coupled with unhygienic conditions of living.
PMCID: PMC3746648  PMID: 23983389
Medicinal plants; CAM; ethnomedicine; Mandai
9.  Ethnomedicinal plants of the Bauri tribal community of Moulvibazar District, Bangladesh 
Ancient Science of Life  2013;32(3):144-149.
Context:
Bangladesh reportedly has more than 100 tribal communities; however, documentation of their medicinal practices is markedly absent.
Aim:
The aim of the present study was to conduct an ethnomedicinal survey among the little known Bauri tribe of Bangladesh, whose tribal medicinal practices are yet to be documented.
Settings and Design:
The survey was carried out among the Bauri tribal community of Purbo Tila village in Moulvibazar District. The community is believed to be the only Bauri community in the country and had four tribal healers who continue their traditional medicinal practices.
Materials and Methods:
Interviews of the healers were carried out with the help of a semi-structured questionnaire and the guided field-walk method where the healers took the interviewers on guided field-walks through areas from where they collected their medicinal plants. Here they identified the plants and described their uses.
Results:
The Bauri healers were observed to use 40 different plant species and one bird species for treatment of ailments such as fever, respiratory tract disorders, pain, gastrointestinal disorders, eye problems like cataract and conjunctivitis, jaundice, abscess, cardiovascular disorders, urinary problems, paralysis, dog bite, snake bite, helminthiasis, lesions on the tongue or lips and piles. Leaves were the major plant part used and constituted 38.3% of total uses followed by fruits at 14.9%.
Conclusions:
A review of the relevant scientific literature showed that a number of medicinal plants used by the Bauri healers possess pharmacological activities, which were in line with the traditional uses, thus validating their use by the Bauri tribe.
doi:10.4103/0257-7941.122997
PMCID: PMC3902534  PMID: 24501442
Bauri; ethnomedicine; Moulvibazar
10.  Antimalarial plants of northeast India: An overview 
The need for an alternative drug for malaria initiated intensive efforts for developing new antimalarials from indigenous plants. The information from different tribal communities of northeast India along with research papers, including books, journals and documents of different universities and institutes of northeast India was collected for information on botanical therapies and plant species used for malaria. Sixty-eight plant species belonging to 33 families are used by the people of northeast India for the treatment of malaria. Six plant species, namely, Alstonia scholaris, Coptis teeta, Crotolaria occulta, Ocimum sanctum, Polygala persicariaefolia, Vitex peduncularis, have been reported by more than one worker from different parts of northeast India. The species reported to be used for the treatment of malaria were either found around the vicinity of their habitation or in the forest area of northeast India. The most frequently used plant parts were leaves (33%), roots (31%), and bark and whole plant (12%). The present study has compiled and enlisted the antimalarial plants of northeast India, which would help future workers to find out the suitable antimalarial plants by thorough study.
doi:10.4103/0975-9476.93940
PMCID: PMC3326788  PMID: 22529674
Alkaloids; malaria; medicinal plants; mosquito repellents; northeast India; traditional knowledge of medicine
11.  Treatment with aquatic plants by a Bagdi tribal healer of Rajbari District, Bangladesh 
Ancient Science of Life  2013;33(1):22-26.
Context:
Tribal healers mainly use land plants in their medicinal formulations; use of aquatic plants has been scarcely reported.
Aims:
The aim of the present study was to conduct an ethnomedicinal survey working with a Bagdi tribal healer of Rajbari District, Bangladesh.
Settings and Design:
The survey was carried out working with a Bagdi healer, who lived alone in the wetlands of Rajbari District and used primarily aquatic plants for treatment.
Materials and Methods:
Interview of the healer was carried out with the help of a semi-structured questionnaire and the guided field-walk method.
Results:
The Bagdi healer was observed to use seven different aquatic plant species coming from five plant families for treatment of ailments such as hemorrhoids, tonsillitis, heart disorders, burning sensations and pain in hands or legs, blurred vision, debility, sexual weakness in males, chronic dysentery, infertility in women, constipation, chronic leucorrhea, blackness and foul odor of menstrual blood, hair loss, graying of hair and to keep the head cool. One plant was used to treat what the healer mentioned as “evil eye”, this refers to their belief in black-magic.
Conclusions:
This is the first reported instance of a Bagdi healer who primarily uses aquatic plants for treatment. Ethnomedicinal uses of a number of the plants used by the Bagdi healer have been reported for other places in India and Pakistan. Taken together, the various uses of the different plant species opens up scientific possibilities of new drug discoveries from the plants.
doi:10.4103/0257-7941.134562
PMCID: PMC4140017  PMID: 25161326
Aquatic plants; Bagdi; Bangladesh; ethnomedicine; Rajbari
12.  Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria 
PLoS Medicine  2009;6(4):e1000055.
Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa.
Background
Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution.
Methods and Findings
We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations.
Conclusions
Resistant dhps has emerged independently in multiple sites in Africa during the past 10–20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.
Editors' Summary
Background
Plasmodium falciparum, a mosquito-borne parasite that causes malaria, kills nearly one million people every year, mostly in sub-Saharan Africa. People become infected with P. falciparum when they are bitten by a mosquito that has acquired the parasite in a blood meal taken from an infected person. P. falciparum malaria, which is characterized by recurring fevers and chills, anemia (loss of red blood cells), and damage to vital organs, can be fatal within hours of symptom onset if untreated. Until recently, treatment in Africa relied on chloroquine and sulfadoxine–pyrimethamine. Unfortunately, parasites resistant to both these antimalarial drugs is now widespread. Consequently, the World Health Organization currently recommends artemisinin combination therapy for the treatment of P. falciparum malaria in Africa and other places where drug-resistant malaria is common. In this therapy, artemisinin derivatives (new fast-acting antimalarial agents) are used in combination with another antimalarial to reduce the chances of P. falciparum becoming resistant to either drug.
Why Was This Study Done?
P. falciparum becomes resistant to antimalarial drugs by acquiring “resistance mutations,” genetic changes that prevent these drugs from killing the parasite. A mutation in the gene encoding a protein called the chloroquine resistance transporter causes resistance to chloroquine, a specific group of mutations in the dihydrofolate reductase gene causes resistance to pyrimethamine, and several mutations in dhps, the gene that encodes dihydropteroate synthase, are associated with resistance to sulfadoxine. Scientists have discovered that the mutations causing chloroquine and pyrimethamine resistance originated in Asia and spread into Africa (probably multiple times) in the late 1970s and mid-1980s, respectively. These Asian-derived mutations are now common throughout Africa and, consequently, it is not possible to determine how they spread across the continent. Information of this sort would, however, help experts design effective measures to control the spread of drug-resistant P. falciparum. Because the mutations in dhps that cause sulfadoxine resistance only began to emerge in the mid-1990s, they haven't spread evenly across Africa yet. In this study, therefore, the researchers use genetic methods to characterize the geographical origins and contemporary distribution of dhps resistance mutations in Africa.
What Did the Researchers Do and Find?
The researchers analyzed dhps mutations in P. falciparum DNA from blood samples collected from patients with malaria in various African countries and searched the scientific literature for other similar studies. Together, these data show that five major variant dhps sequences (three of which contain mutations that confer various degrees of resistance to sulphadoxine in laboratory tests) are currently present in Africa, each with a unique geographical distribution. In particular, the data show that P. falciparum parasites in east and west Africa carry different resistance mutations. Next, the researchers looked for microsatellite variants in the DNA flanking the dhps gene. Microsatellites are DNA regions that contain short, repeated sequences of nucleotides. Because the number of repeats can vary and because microsatellites are inherited together with nearby genes, the ancestry of various resistance mutations can be worked out by examining the microsatellites flanking different mutant dhps genes. This analysis revealed five regional clusters in which the same resistance lineage was present at all the sites examined within the region and also showed that the resistance mutations in east and west Africa have a different ancestry.
What Do These Findings Mean?
These findings show that sulfadoxine-resistant P. falciparum has recently emerged independently at multiple sites in Africa and that the molecular basis for sulfadoxine resistance is different in east and west Africa. This latter result may have clinical implications because it suggests that the effectiveness of sulfadoxine as an antimalarial drug may vary across the continent. Finally, although many more samples need to be analyzed to build a complete picture of the spread of antimalarial resistance across Africa, these findings suggest that economic and transport infrastructures may have played a role in governing recent parasite dispersal across this continent by affecting human migration. Thus, coordinated malaria control campaigns across socioeconomically linked areas in Africa may reduce the African malaria burden more effectively than campaigns that are confined to national territories.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000055.
This study is further discussed in a PLoS Medicine Perspective by Tim Anderson
The MedlinePlus encyclopedia contains a page on malaria (in English and Spanish)
Information is available from the World Health Organization on malaria (in several languages) and on drug-resistant malaria
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish)
Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria, and on malaria control efforts in specific parts of the world
The WorldWide Antimalarial Resistance Network is creating an international database about antimalarial drug resistance
doi:10.1371/journal.pmed.1000055
PMCID: PMC2661256  PMID: 19365539
13.  Medicinal Plants and Formulations Used by the Soren Clan of the Santal Tribe in Rajshahi District, Bangladesh for Treatment of Various Ailments 
The Santals form the largest tribal community in northern Bangladesh reside primarily in Rajshahi and Rangpur Divisions, where they live in the districts of Rajshahi, Rangpur, Thakurgaon, Dinajpur, and Panchagarh. Although they are fast losing their traditional medicinal practices, they still have their own medicinal practitioners who rely mostly on medicinal plants for treatment of a variety of ailments. The traditional medicinal practices vary quite extensively between the twelve clans of the Santals. The objective of the present study was to conduct an ethnomedicinal survey amongst the Soren clan of the Santal community residing in two villages of Tanor Santal Para in Rajshahi district to collect information on their use of medicinal plants. Interviews were conducted of the two existing Santal traditional medicinal practitioners of the Soren clan with the help of a semi-structured questionnaire and using the guided field-walk method. Plant specimens as pointed out by the practitioners were collected and pressed on the field and identification completed at the Bangladesh National Herbarium. Information on 53 medicinal plants distributed into 32 families was obtained in this survey. Ailments treated by these plants included skin disorders, respiratory tract disorders, gastro-intestinal disorders, sexual dysfunctions, sexually transmitted diseases, diabetes, helminthiasis, pain, urinary problems, filariasis, leprosy, tuberculosis, epilepsy, snake bite, enlarged heart, and paralysis. The medicinal plants used by the Santals merit further scientific studies for some of their formulations are used to treat diseases like diabetes, paralysis, enlarged heart, tuberculosis, and filariasis for which modern medicine has no known cure or medicines have developed resistant vectors.
PMCID: PMC3746673  PMID: 23983366
Asian medicine; CAM; ethnomedicine; alternative therapy
14.  Antimalarial natural products: a review 
Objective: Malaria is an infectious disease commonplace in tropical countries. For many years, major antimalarial drugs consisted of natural products, but since 1930s these drugs have been largely replaced with a series of synthetic drugs. This article tries to briefly indicate that some plants which previously were used to treat malaria, as a result of deficiencies of synthetic drugs, have revived into useful products once more. It also attempts to describe some tests which can be used to evaluate plant extracts for antimalarial activity.
Materials and Methods: By referring to some recent literatures, data were collected about plants used for the treatment of malaria, evaluation of plant extracts for antimalarial activity, modes of action of natural antimalarial agents, and recent research on antimalarial plants in Iran and other countries.
Results and Conclusion: There is an urgent need for the development of new treatments for malaria. Many countries have a vast precedence in the use of medicinal plants and the required knowledge spans many centuries. Although malaria is controlled in Iran, some researchers tend to study malaria and related subjects. In vitro biological tests for the detection of antimalarial activities in plant extracts are currently available. It is vital that the efficacy and safety of traditional medicines be validated and their active constituents be identified in order to establish reliable quality control measures.
PMCID: PMC4075661  PMID: 25050231
Antimalarial plants; Malaria; Natural Products
15.  Traditional Knowledge and Formulations of Medicinal Plants Used by the Traditional Medical Practitioners of Bangladesh to Treat Schizophrenia Like Psychosis 
Schizophrenia is a subtle disorder of brain development and plasticity; it affects the most basic human processes of perception, emotion, and judgment. In Bangladesh the traditional medical practitioners of rural and remote areas characterized the schizophrenia as an insanity or a mental problem due to possession by ghosts or evil spirits and they have used various plant species' to treat such symptoms. The aim of the present study was to conduct an ethnomedicinal plant survey and documentation of the formulations of different plant parts used by the traditional medical practitioners of Rangamati district of Bangladesh for the treatment of schizophrenia like psychosis. It was observed that the traditional medical practitioners used a total of 15 plant species to make 14 formulations. The plants were divided into 13 families, used for treatment of schizophrenia and accompanying symptoms like hallucination, depression, oversleeping or insomnia, deterioration of personal hygiene, forgetfulness, and fear due to evil spirits like genies or ghost. A search of the relevant scientific literatures showed that a number of plants used by the medicinal practitioners have been scientifically validated in their uses and traditional medicinal knowledge has been a means towards the discovery of many modern medicines. Moreover, the antipsychotic drug reserpine, isolated from the dried root of Rauvolfia serpentina species, revolutionized the treatment of schizophrenia. So it is very much possible that formulations of the practitioner, when examined scientifically in their entireties, can form discovery of lead compounds which can be used as safe and effective antipsychotic drug to treat schizophrenia.
doi:10.1155/2014/679810
PMCID: PMC4100298  PMID: 25101175
16.  The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites 
PLoS Medicine  2012;9(2):e1001169.
Michael Delves and colleagues compare the activity of 50 current and experimental antimalarials against liver, sexual blood, and mosquito stages of selected human and nonhuman parasite species, including Plasmodium falciparum, Plasmodium berghei, and Plasmodium yoelii.
Background
Malaria remains a disease of devastating global impact, killing more than 800,000 people every year—the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance.
Methods and Findings
Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony.
Conclusions
These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle–wide analyses of drugs for other pathogens with complex life cycles.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria is a life-threatening disease caused by the Plasmodium parasite, which is transmitted to people through the bites of infected mosquitoes. According to latest global estimates, about 250 million people are infected with malaria every year with roughly 800,000 deaths—most occurring among young children living in Africa. Malaria also causes severe morbidity in children, such as anemia, low birth weight, and neurological problems, which compromise the health and development of millions of children living in malaria endemic areas. In addition to strategies that scale up and roll out the prevention of malaria, such as country-wide programs to provide insecticide-treating bednets, in the goal to eradicate malaria, the global health community has refocused efforts on the treatment of malaria, including finding new compounds that target different stages of the parasite life cycle as it passes from vector to host and back.
The interruption of malaria transmission worldwide is one of the greatest challenges for the global health community. In January 2011, this journal published a series on The Malaria Eradication Research Agenda (malERA), which described a set of research and development priorities, identified key knowledge gaps and the necessary tools needed, and introduced a draft research and development agenda for the worldwide eradication of malaria.
Why Was This Study Done?
Most currently available antimalarial drugs primarily target the disease-causing parasites' stages in the human blood system. But to eradicate malaria, new drugs that block transmission of the parasite between the human host and the mosquito vector, and eliminate the various stages of the parasite during its cycle in the human body, are needed. In this laboratory study, the researchers compared the profiles of all available and experimental antimalarials and analyzed each drug for activity against each specific stage in the malaria parasite's life cycle to provide a reference set of methods and data, that might serve as a benchmark to help guide the malaria research community in assessing the potential of newly discovered antimalarials. Furthermore, this analysis could provide insights into which chemical drug classes might provide transmission-blocking capabilities—an essential component of malaria eradication.
What Did the Researchers Do and Find?
The researchers used novel laboratory techniques under standardized conditions to develop a series of novel assays to analyze the activities of 50 antimalarial compounds (current drugs and those under development) against three Plasmodium species encompassing every major cellular strategy of the malarial life cycle including drug resistant parasite strains. In their comparative analysis, the researchers undertook a chemical profiling approach to identify the drugs that block transmission from the host to the mosquito vector and additionally suppress transmission from the mosquito to the human host.
The researchers highlighted some encouraging results; for example, the potencies of some antimalarials against the asexual blood stage of cultivated P. falciparum and P. vivax isolates show a very good correlation, suggesting that most of the pathways inhibited by antimalarials in P. falciparum may also be valid targets in P. vivax. The researchers also have shown that approved drugs, such as pyronaridine and atovaquone, can target liver and sexual stages in addition to asexual blood stages. Furthermore, the researchers found promising results for new compounds currently in clinical trials, such as the endoperoxide OZ439, a stable synthetic molecule currently being studied in a phase IIa clinical trial, which seemed to be a strong inhibitor of gametocyte maturation and gamete formation. The new 8-aminoquinoline, NPC-1161B, also inhibited sporogony.
What Do These Findings Mean?
The results of this analysis provide a valuable guide to help researchers decide which drugs and compounds show most promise as potential future antimalarial drugs for blocking the transmission of malaria. This study could also help researchers make decisions about which molecules could be best combined to provide the next generation of drugs that will succeed artemisinin compound therapy and support the eradication of malaria. Furthermore, this comprehensive approach to drug discovery could be applied to test drugs against other pathogens with complex life cycles.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001169.
The malERA a research agenda for malaria eradication sponsored collection, published by PLoS in January 2011, comprises 12 Review articles that discuss agendas in malaria research and development
doi:10.1371/journal.pmed.1001169
PMCID: PMC3283556  PMID: 22363211
17.  Ethnomedicinal plants used for the treatment of cuts and wounds by Kuruma tribes, Wayanadu districts of Kerala, India 
Objective
To study the ethnomedicinal uses by the Kuruma tribals for discovering new drugs to cure cuts and wounds so as to provid the data scientifically evaluated.
Methods
A survey was conducted during May 2008–September 2009 to collect information on medicinal plants used by the Kuruma tribes and queries were made on the various species of plants used regularly and occasionally to cure cuts and wounds.
Results
The present study includes information on 34 plant species belonging to 32 genera and 25 families used by Kuruma tribe of Wayanad district of Kerala for the treatment of cuts and wounds.
Conclusions
The present study of the knowledge on the folklore uses of the medicinal plants used by Kuruma tribes leads to effective utilization of herbal medicines in the future.
doi:10.12980/APJTB.4.2014B571
PMCID: PMC4025284  PMID: 25183135
Ethnomedicine; Kuruma tribe; Cuts; Wounds; Wayanad; Kerala
18.  Population Pharmacokinetics of Artesunate and Dihydroartemisinin following Intra-Rectal Dosing of Artesunate in Malaria Patients 
PLoS Medicine  2006;3(11):e444.
Background
Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria.
Methods and Findings
Adults and children in Africa and Southeast Asia with moderately severe malaria were recruited in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24 h following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36–1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the posterior individual estimates of V/F, CL/F, and AUC0–6h were observed.
Conclusions
The pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations.
A study of the population pharmacokinetics of intra-rectal artesunate in patients with moderately severe falciparum malaria found the pharmacokinetic properties of dihydroartemisinin were affected only by gender and body weight.
Editors' Summary
Background.
More than 40% of the world's population is at risk of malaria, a tropical parasitic disease that is transmitted between people by infected mosquitoes. Malaria parasites cause a 'flu-like illness that includes chills, fevers, headaches, and sometimes nausea and vomiting. If untreated, people with malaria can rapidly become anemic—the parasite destroys their red blood cells—or can develop complications that damage the brain and other organs. Severe malaria can be fatal and must be treated quickly. It has become a matter of great concern that the parasite has developed resistance to most of the drugs used to treat or prevent malaria. In the past few years, artemisinin derivatives have been shown to be an effective new form of treatment. Artemisinin derivatives are effective, rapid-acting antimalarial drugs—wormwood, the plant source of artemisinin, is an ancient Chinese cure for malaria. Artesunate, a water-soluble derivative of artemisinin, can be given as tablets or as injections. However, people with severe malaria often cannot take oral medicines, and in rural settings in the developing world, artesunate injections are usually impracticable. Consequently, rectal artesunate suppositories have been developed to provide first-line treatment of severe malaria in these settings. This simple dosing method can “buy” patients valuable time during which they can be moved to a hospital for further treatment.
Why Was This Study Done?
When treating severe malaria, it is important that every patient absorbs the antimalarial drug rapidly and efficiently into their blood. If even a small proportion of patients malabsorb the drug, many people could die. How the body processes a drug is known as pharmacokinetics, and although some pharmacokinetic studies have investigated how the body processes artesunate given in rectal suppositories, relatively little is know about the population pharmacokinetics of artesunate given this way. That is, the patient characteristics that affect the processing of intra-rectal artesunate are not known, and it is unclear whether a small proportion of the population might fail to absorb the drug given via this route. In this study, the researchers have developed and tested a population pharmacokinetic model for artesunate given rectally to children and adults with moderately severe malaria.
What Did the Researchers Do and Find?
The researchers took serial blood samples from nearly 200 patients with moderately severe malaria in Africa and Southeast Asia for the first 24 hours after they received a rectal artesunate suppository. They measured the levels of artesunate and dihydroartemisinin (DHA; the body rapidly converts artesunate to DHA, which kills the malaria parasites) in these samples and used these data to build a pharmacokinetic model for how the body processes. Averaged out across the patients, they calculated, for example, that half of the drug present absorbed was eliminated within 43 minutes. To find out whether any patient characteristics affected the pharmacokinetics of intra-rectal artesunate, the researchers used their model to estimate the clearance of DHA from the body and the ability of DHA to spread through the body (so-called apparent volume of distribution) for the study patients. This analysis showed that only gender and weight affected DHA pharmacokinetics. Finally, the researchers showed that how well the parasite was cleared from the patients was not related to these pharmacokinetic parameters, although the need for earlier rescue treatment was associated with a larger volume of distribution for DHA. Importantly, the parasitological response was not affected by the estimated cumulative amount of DHA absorbed into the blood during the first six hours after treatment.
What Do These Findings Mean?
The data presented in this study indicate that individual patients processed artesunate very differently in terms of how they absorbed the drug and how it spread around the body. Even so, the maximal effects of artesunate on the malaria parasite were achieved rapidly in nearly all the patients. This and other pharmacokinetic findings must be interpreted with caution, warn the researchers, because their model included many assumptions to allow, for example, for the variability of DHA concentrations both within individual patients and between patients. Nevertheless, the findings provide important clues about which patient characteristics might cause early treatment failure, and indicate that artesunate is sufficiently well absorbed via the rectal route in most patients to make artesunate suppositories a promising first-line treatment for moderately severe malaria.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030444.
• World Health Organization links to general information on malaria plus specific information on rectal artesunate
• MedlinePlus encyclopedia entry on malaria
• US Centers for Disease Control and Prevention information on malaria for patients and professionals
• Wikipedia pages on malaria and artemisinin (note that Wikipedia is a free online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030444
PMCID: PMC1664603  PMID: 17132053
19.  Traditional use of medicinal plants by the Jaintia tribes in North Cachar Hills district of Assam, northeast India 
The study of ethnobotany relating to any tribe is in itself a very intricate or convoluted process. This paper documents the traditional knowledge of medicinal plants that are in use by the indigenous Jaintia tribes residing in few isolated pockets of northeast India. The present study was done through structured questionnaires in consultations with the tribal practitioners and has resulted in the documentation of 39 medicinal plant species belonging to 27 families and 35 genera. For curing diverse form of ailments, the use of aboveground plant parts was higher (76.59%) than the underground plant parts (23.41%). Of the aboveground plant parts, leaf was used in the majority of cases (23 species), followed by fruit (4). Different underground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were also found to be in use by the Jaintia tribe as a medicine. Altogether, 30 types of ailments have been reported to be cured by using these 39 medicinal plant species. The study thus underlines the potentials of the ethnobotanical research and the need for the documentation of traditional ecological knowledge pertaining to the medicinal plant utilization for the greater benefit of mankind.
doi:10.1186/1746-4269-2-33
PMCID: PMC1563446  PMID: 16899114
20.  Traditional healing practice and folk medicines used by Mishing community of North East India 
Assam and Arunachal Pradesh have very rich tradition of herbal medicines used in the treatment of various ailments. Tribal communities practice different types of traditional healing practices. Enough documentation is available on the healing practices in other tribal communities except Mishing community of Assam and foot hill of East Siang district of Arunachal Pradesh hence the attempt was made for the same. A survey on folk medicinal plants and folk healers of Mishing tribe was conducted in few places of Lakhimpur and Dhemaji district of Assam and East Siang district of Arunachal Pradesh, where this ethnic group is living since time immemorial. All information was collected based on interview and field studies with local healers within the community. The identification of medicinal plants collected with help of indigenous healers was done. Such medicines have been shown to have significant healing power, either in their natural state or as the source of new products processed by them. This study is mainly concentrated with plants used to cure diseases and to enquire about different healing systems. Detail note on the method of preparation of precise dose, the part/parts of plants used and method of application is given.
doi:10.4103/0975-9476.100171
PMCID: PMC3487237  PMID: 23125508
Ethno-medicines; ethnic groups; herbal practitioners
21.  Intermittent Preventive Treatment of Malaria Provides Substantial Protection against Malaria in Children Already Protected by an Insecticide-Treated Bednet in Burkina Faso: A Randomised, Double-Blind, Placebo-Controlled Trial 
PLoS Medicine  2011;8(2):e1000408.
A randomized trial reported by Diadier Diallo and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes using insecticide-treated bednets provides substantial protection from malaria.
Background
Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN).
Methods and Findings
An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥5,000/µl, was 2.88 (95% confidence interval [CI] 2.70–3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78–0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%–74%) (p<0.001). There was a 69% (95% CI 6%–90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%–69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%–77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%–70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65–1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72–0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3–3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded.
Conclusions
IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission.
Trial Registration
ClinicalTrials.gov NCT00738946
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria accounts for one in five of all childhood deaths in Africa and of the one million annual malarial deaths world-wide, over 75% occur in African children under 5 years old. Malaria also causes severe morbidity in children, such as anemia, low birth weight, and neurological problems, which compromise the health and development of millions of children living in malaria endemic areas. As much of the impact of malaria on African children can be effectively prevented, significant efforts have been made in recent years to improve malaria control, such as the implementation of intermittent preventive treatment of malaria.
Intermittent preventive treatment (IPT) involves administration of antimalarial drugs at defined time intervals to individuals, regardless of whether they are known to be infected with malaria, to prevent morbidity and mortality. IPT was initially recommended for pregnant women and recently this strategy was extended to include infants (IPTi). Now, there is also IPT of malaria in children (IPTc), which is designed to protect against malaria during the high malaria transmission season.
Why Was This Study Done?
Large clinical trials have shown that IPTc involving the administration of two to three doses of an antimalarial drug (sulphadoxine pyrimethamine [SP] and artesunate [AS] or amodiaquine [AQ]) during the high malaria transmission season effectively reduces the incidence of malaria. However, these studies were conducted in countries where the use of insecticide-treated bednets—an intervention that provides at least 50% protection against morbidity from malaria and is the main tool used for malaria control in most of sub-Saharan Africa—was relatively low. Therefore, it is unclear whether IPTc will be as effective in children who sleep under insecticide-treated bednets as has been previously shown in communities where insecticide-treated bednet usage is low. So to determine the answer to this important question, the researchers conducted a randomized, placebo-controlled trial of IPTc with SP + AQ (chosen because of the effectiveness of this combination in a pilot study) in children who slept under an insecticide-treated bednet in an area of seasonal malaria transmission in Burkina Faso.
What Did the Researchers Do and Find?
The researchers enrolled 3,014 eligible children aged 3–59 months into a randomized double-blind, placebo-controlled trial during the 2008 malaria transmission season in Burkina Faso. All children were given a long-lasting insecticide-treated bednet at the start of the study with instructions to their family on the correct use of the net. Children were then randomized into two arms—1,509 were allocated to the intervention group and 1,505 to the control group—to receive three courses of IPTc with SP plus AQ or placebos given at monthly intervals during the peak malaria transmission season. The researchers monitored the incidence of malaria throughout the malaria season and also monitored the use of long-lasting insecticide-treated bednets throughout the study period. In addition, researchers conducted a cross-sectional survey in 150 randomly selected children every week and in every child enrolled in the trial 6 weeks after the last course of IPTc, to measure their temperature, height and weight, and blood hemoglobin and parasite count levels.
The number of children who slept under their long-lasting insecticide-treated bednet was similar in both arms. During the intervention period, the researchers found that the incidence of clinical malaria (defined as fever or a history of fever and the presence of at least 5,000 asexual forms of P. falciparum per microliter) was 2.88 in the control arm versus 0.87 in the intervention arm—giving a protective efficacy of 70%. There were 13 cases of severe malaria in the control arm and four in the IPTc arm—a 69% reduction in incidence. Additionally, all-cause hospital admission rate was reduced by 46%. At the end of the malaria transmission period, IPTc reduced the proportion of children infected with malaria parasites by 73% and reduced anemia by 33%. In addition, IPTc appeared to reduce the risk of wasting (risk ratio  = 0.79) and of being underweight (risk ratio  = 0.84). However, children who received IPTc were almost three times more likely to vomit than children who received placebo but there were no drug-related serious adverse events.
What Do These Findings Mean?
The results of this study show that in peak malarial transmission season in Burkina Faso, IPTc provides substantial additional protection against episodes of clinical malaria, severe malaria, and all-cause hospital admissions in children sleeping under long-lasting insecticide-treated bednets. In addition, intermittent preventive treatment of malaria with SP plus AQ appears to be safe for use in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000408.
This topic is further discussed in two PLoS Medicine research articles: Dicko et al. and Bojang et al., and in a PLoS Medicine Perspective by Beeson
Roll Back Malaria has information about malaria in children, including intervention strategies
UNICEF also provides comprehensive information about malaria in children
The Intermittent Preventive Treatment in Infants Consortium (ipti) provides information on intermittent preventive treatment in infants
Roll Back Malaria has an information sheet on insecticide-treated bednets
doi:10.1371/journal.pmed.1000408
PMCID: PMC3032552  PMID: 21304925
22.  Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity 
PLoS Medicine  2008;5(11):e226.
Background
Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas.
Methods and Findings
We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting.
Conclusions
Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.
Lucy Okell and colleagues predict the impact on transmission outcomes of ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania.
Editors' Summary
Background.
Plasmodium falciparum, a mosquito-borne parasite that causes malaria, kills nearly one million people every year. When an infected mosquito bites a person, it injects a life stage of the parasite called sporozoites, which invade human liver cells where they initially develop. The liver cells then release merozoites (another life stage of the parasite). These invade red blood cells where they multiply before bursting out and infecting more red blood cells, which can cause fever and damage vital organs. Some merozoites develop into gametocytes, which infect mosquitos when they take a blood meal. In the mosquito, the gametocytes give rise to sporozoites, thus completing the parasite's life cycle. Because malaria parasites are now resistant to many antimalarial drugs, the preferred first-line treatment for P. falciparum malaria in most countries is artemisinin combination therapy (ACT). Artemisinin derivatives are fast-acting antimalarial agents that, unlike previous first-line treatments, reduce the number of gametocytes in patients' blood, making them less infectious to mosquitos, and therefore have more potential to reduce malaria transmission. These compounds are used in combination with another antimalarial drug to reduce the chances of P. falciparum becoming resistant to either drug.
Why Was This Study Done?
Because malaria poses such a large global public-health burden, there is considerable national and international interest in eliminating it or at least minimizing its transmission. Malaria control agencies need to know how to choose between available types of ACT as well as other antimalarials so as to not only cure malaria illness but also prevent transmission as much as possible. The financial resources available to control malaria are limited, so for planning integrated transmission reduction programs it is important for policy makers to know what contribution their treatment policy could make in addition to other control strategies (for example, the provision of insecticide-treated bed nets to reduce mosquito bites) to reducing transmission. Furthermore, in areas with high levels of malaria, it is uncertain to what extent treatment can reduce transmission since many infected people are immune and do not suffer symptoms or seek health care, but continue to transmit to others. In this study, the researchers develop a mathematical model to predict the impact on malaria transmission of the introduction of ACT and alternative first-line treatments for malaria in six regions of Tanzania with different levels of malaria transmission.
What Did the Researchers Do and Find?
The researchers developed a “deterministic compartmental” model of malaria transmission in human and mosquito populations and included numerous variables likely to affect malaria transmission (variables were based on data collected in Tanzania just before the introduction of ACT). They then used the model to estimate the impact on malaria transmission of introducing ACT or other antimalarial drugs with different properties. The model predicted that the percentage reduction in the prevalence of infection (the fraction of the population with malaria) and the incidence of infection (the number of new cases in the population per year) associated with a 100% switch to ACT would be greater in areas with low initial transmission rates than in areas with high transmission rates. For example, in the area with the lowest initial transmission rates, the model predicted that the prevalence of infection would drop by 53%, but in the area with the highest initial transmission rate, the drop would be only 11%. However, because more people get malaria in high-transmission areas, the total number of malaria illness episodes prevented would be ten times higher in the area with highest transmission than in the area with lowest transmission. The model also predicted that, in areas with high transmission, long-acting treatments which protect patients from reinfection would reduce transmission more effectively than some common currently used ACT regimens which are gametocyte-killing but short-acting. Treatments which were both long-acting and gametocyte-killing were predicted to have the biggest impact across all settings.
What Do These Findings Mean?
As with all mathematical models, the accuracy of the predictions made by this model depend on the many assumptions incorporated into the model. In addition, because data from Tanzania were fed into the model, its predictions are to some extent specific to the area. Nevertheless the Tanzanian setting is typical of sub-Saharan malaria-affected areas, and the authors show that varying their assumptions and the data fed into the model within realistic ranges in most cases does not substantially change their overall conclusions. The findings in this study suggest that in low-transmission areas, provided ACT is widely used, ACT may reduce malaria transmission as effectively as the widespread use of insecticide-treated bed nets. The findings also suggest that the use of longer-acting regimens with or without artemisinin components might be a good way to reduce transmission in high-transmission areas, provided the development of parasite resistance can be avoided. More generally, these findings suggest that public-health officials need to take the properties of antimalarial drugs into account together with the levels of transmission in the area when designing policies in order to achieve the highest impact on malaria transmission.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050226.
This study is further discussed in a PLoS Medicine Perspective by Maciej Boni and colleagues
The MedlinePlus encyclopedia contains a page on malaria (in English and Spanish)
Information is available from the World Health Organization on malaria (in several languages)
The US Centers for Disease Control and Prevention provides information on malaria (in English and Spanish)
Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria, on artemisinin-based combination therapies, and on malaria in Tanzania
doi:10.1371/journal.pmed.0050226
PMCID: PMC2586356  PMID: 19067479
23.  Indigenous knowledge of medicinal plants used by Saperas community of Khetawas, Jhajjar District, Haryana, India 
Background
Plants have traditionally been used as a source of medicine in India by indigenous people of different ethnic groups inhabiting various terrains for the control of various ailments afflicting human and their domestic animals. The indigenous community of snake charmers belongs to the 'Nath' community in India have played important role of healers in treating snake bite victims. Snake charmers also sell herbal remedies for common ailments. In the present paper an attempt has been made to document on ethno botanical survey and traditional medicines used by snake charmers of village Khetawas located in district Jhajjar of Haryana, India as the little work has been made in the past to document the knowledge from this community.
Methods
Ethno botanical data and traditional uses of plants information was obtained by semi structured oral interviews from experienced rural folk, traditional herbal medicine practitioners of the 'Nath' community. A total of 42 selected inhabitants were interviewed, 41 were male and only one woman. The age of the healers was between 25 years and 75 years. The plant specimens were identified according to different references concerning the medicinal plants of Haryana and adjoining areas and further confirmation from Forest Research Institute, Dehradun.
Results
The present study revealed that the people of the snake charmer community used 57 medicinal plants species that belonged to 51 genera and 35 families for the treatment of various diseases. The study has brought to light that the main diseases treated by this community was snakebite in which 19 different types of medicinal plants belongs to 13 families were used. Significantly higher number of medicinal plants was claimed by men as compared to women. The highest numbers of medicinal plants for traditional uses utilized by this community were belonging to family Fabaceae.
Conclusion
This community carries a vast knowledge of medicinal plants but as snake charming is banned in India as part of efforts to protect India's steadily depleting wildlife, this knowledge is also rapidly disappearing in this community. Such type of ethno botanical studies will help in systematic documentation of ethno botanical knowledge and availing to the scientific world plant therapies used as antivenin by the Saperas community.
doi:10.1186/1746-4269-6-4
PMCID: PMC2826346  PMID: 20109179
24.  Impact of Intermittent Screening and Treatment for Malaria among School Children in Kenya: A Cluster Randomised Trial 
PLoS Medicine  2014;11(1):e1001594.
Katherine Halliday and colleagues conducted a cluster randomized controlled trial in Kenyan school children in an area of low to moderate malaria transmission to investigate the effect of intermittent screening and treatment of malaria on health and education.
Please see later in the article for the Editors' Summary
Background
Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST) for malaria on the health and education of school children in an area of low to moderate malaria transmission.
Methods and Findings
A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010–2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs), and children (with or without malaria symptoms) found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL). Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis.
During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93–1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90–1.11, p = 0.953) respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in the younger class at 9 and 24 months and on arithmetic scores at 24 months.
Conclusion
In this setting in Kenya, IST as implemented in this study is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following AL treatment, the variable reliability of RDTs, and the relative contribution of malaria to the aetiology of anaemia in this setting.
Trial registration
www.ClinicalTrials.gov NCT00878007
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than 200 million cases of malaria occur worldwide and more than 600,000 people, mostly children living in sub-Saharan Africa, die from this mosquito-borne parasitic infection. Malaria can be prevented by controlling the night-biting mosquitoes that transmit Plasmodium parasites and by sleeping under insecticide-treated nets to avoid mosquito bites. Infection with malaria parasites causes recurring flu-like symptoms and needs to be treated promptly with antimalarial drugs to prevent the development of anaemia (a reduction in red blood cell numbers) and potentially fatal damage to the brain and other organs. Treatment also reduces malaria transmission. In 1998, the World Health Organization and several other international bodies established the Roll Back Malaria Partnership to provide a coordinated global approach to fighting malaria. In 2008, the Partnership launched its Global Malaria Action Plan, which aims to control malaria to reduce the current burden, to eliminate malaria over time country by country, and, ultimately, to eradicate malaria.
Why Was This Study Done?
In recent years, many malaria-endemic countries (countries where malaria is always present) have implemented successful malaria control programs and reduced malaria transmission levels. In these countries, immunity to malaria is now acquired more slowly than in the past, the burden of clinical malaria is shifting from very young children to older children, and infection rates with malaria parasites are now highest among school-aged children. Chronic untreated Plasmodium infection, even when it does not cause symptoms, can negatively affect children's health, cognitive development (the acquisition of thinking skills), and educational achievement. However, little is known about how school-based malaria interventions affect the health of children or their educational outcomes. In this cluster randomized trial, the researchers investigate the effect of intermittent screening and treatment (IST) of malaria on the health and education of school children in a rural area of southern Kenya with low-to-moderate malaria transmission. Cluster randomized trials compare the outcomes of groups (“clusters”) of people randomly assigned to receive alternative interventions. IST of malaria involves periodical screening of individuals for Plasmodium infection followed by treatment of everyone who is infected, including people without symptoms, with antimalarial drugs.
What Did the Researchers Do and Find?
The researchers enrolled more than 5,000 children aged between 5 and 20 years from 101 government primary schools in Kenya into their 24-month study. Half the schools were randomly selected to receive the IST intervention (screening once a school term for infection with a malaria parasite with a rapid diagnostic test [RDT] and treatment of all RDT-positive children, with or without malaria symptoms, with six doses of artemether-lumefantrine), which was delivered to randomly selected children from classes 1 and 5 (which contained younger and older children, respectively). During the study, 17.5% of the children in the intervention schools were RDT-positive at screening on average. The prevalences of anaemia and parasitemia (the proportion of children with anaemia and the proportion who were RDT-positive, respectively) were similar in the intervention and control groups at the 12-month and 24-month follow-up and there was no difference between the two groups in classroom attention scores at the 9-month and 24-month follow-up. The IST intervention also had no effect on educational achievement in the older class but, unexpectedly, appeared to have a negative effect on spelling and arithmetic scores in the younger class.
What Do These Findings Mean?
These findings indicate that, in this setting in Kenya, IST as implemented in this study provided no health or education benefits to school children. The finding that the educational achievement of younger children was lower in the intervention group than in the control group may be a chance finding or may indicate that apprehension about the finger prick needed to take blood for the RDT had a negative effect on the performance of younger children during educational tests. The researchers suggest that their failure to demonstrate that the school-based IST intervention they tested had any long-lasting health or education benefits may be because, in a low-to-moderate malaria transmission setting, most of the children screened did not require treatment and those who did lived in focal high transmission regions, where rapid re-infection occurred between screening rounds. Importantly, however, these findings suggest that school screening using RDT could be an efficient way to identify transmission hotspots in communities that should be targeted for malaria control interventions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001594.
This study is further discussed in a PLOS Medicine Perspective by Lorenz von Seidlein
Information is available fro m the World Health Organization on malaria (in several languages); the 2012 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including a selection of personal stories about children with malaria
Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan (in English and French); its website includes a fact sheet about malaria in Kenya
MedlinePlus provides links to additional information on malaria (in English and Spanish)
More information about this trial is available
More information about malaria control in schools is provided in the toolkit
doi:10.1371/journal.pmed.1001594
PMCID: PMC3904819  PMID: 24492859
25.  A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial 
PLoS Medicine  2011;8(11):e1001119.
The Four Artemisinin-Based Combinations (4ABC) Study Group reports a randomized, non-inferiority trial comparing the efficacy and safety of four ACTs in children with mild Plasmodium falciparum malaria from seven sub-Saharan African countries.
Background
Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.
Methods and Findings
Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6–59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37–0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41–1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28–0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21–0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30–0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26–0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.
Conclusions
This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.
Trial Registration
ClinicalTrials.gov NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria is a global public-health problem. Half the world's population is at risk of this mosquito-borne parasitic disease, which kills a million people (mainly children living in sub-Saharan Africa) every year. Although several parasites cause malaria, Plasmodium falciparum is responsible for most of these deaths. During the second half of the 20th century, the main treatments for malaria were inexpensive “monotherapies” such as chloroquine and sulfadoxine-pyrimethamine. Unfortunately, the malaria parasite quickly developed resistance to many of these monotherapies, and in the 1990 s, there was a widespread upsurge in P. falciparum malaria. To combat this increase, the World Health Organization (WHO) now recommends artemisinin-based combination therapy (ACT) for first-line treatment of P. falciparum malaria in all regions where there is drug-resistant malaria. In ACT, artemisinin derivatives (new, fast-acting antimalarial drugs) are used in combination with another antimalarial drug (a partner drug) to reduce the chances of P. falciparum becoming resistant to either drug.
Why Was This Study Done?
WHO currently recommends five ACTs—amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), artesunate-mefloquine, and artesunate-sulfadoxine-pyrimethamine—for the treatment of malaria. Its treatment guidelines state that the choice of ACT in a country or region should be based on the local level of resistance to the non-artemisinin-based partner drug in the combination. However, data on resistance levels to these partner drugs are scarce or unavailable for many sub-Saharan African countries. To help these countries make an informed choice about their national antimalarial treatment policies, in this randomized, non-inferiority trial, the researchers compare the efficacy and safety of four ACTs in African children with uncomplicated (mild) P. falciparum malaria. In a randomized trial, groups of randomly chosen patients with a specific disease are given different treatments and then followed to compare the outcomes of these interventions. A non-inferiority trial investigates whether one treatment is not worse than another treatment.
What Did the Researchers Do and Find?
Each of twelve sites in seven sub-Saharan African countries compared three ACTs out of ASAQ, DHAPQ, AL, and chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 young children with uncomplicated malaria were treated with ACT, actively followed up for 28 days (their parents brought them back to the site for pre-arranged check-ups), and passively followed up for six months (parents brought their children back if they developed any illnesses). At each visit, blood samples were examined for the presence of parasites, and a technique called PCR was used to determine which cases of malaria were new infections and which were recurrences of the original infection. The researchers then calculated the percentage of patients with no infection or with a new infection (the PCR-adjusted adequate clinical and parasitological response [ACPR]) and the percentage of patients with no infection (the PCR-unadjusted ACPR). For the PCR-adjusted efficacy, three pair-wise comparisons (DHAPQ versus AL, DHAPQ versus ASAQ, and ASAQ versus AL) showed non-inferiority at 28 days. That is, for example, similar percentages of patients given DHAPQ or AL (97.3% and 95.5%, respectively) had either no infection or a new infection. CD+A was less efficacious than the other three treatments. For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ and ASAQ; DHAPQ had a higher efficacy than ASAQ, but non-inferiority could not be excluded. That is, the difference in efficacy of these two drugs might have happened by chance.
What Do These Findings Mean?
These findings suggest that AL, ASAQ, and DHAPQ are all efficacious for the treatment of uncomplicated malaria in children; CD+A was withdrawn partway through the trial because of side effects, but these findings also suggest that it was less efficacious than the other ACTs. Importantly, the PCR-unadjusted results indicate that the risk of children becoming re-infected with malaria parasites soon after treatment was lowest for DHAPQ, followed by ASAQ, and then AL. Because these findings are based on pooled results from seven sub-Saharan African countries, they are likely to be generalizable and thus of use in setting national antimalarial drug policies throughout the region. AL and ASAQ are already included in the antimalarial drug policies of many sub-Saharan African countries, note the researchers, but these findings support the WHO recommendation that DHAPQ should also be considered for the treatment for uncomplicated P. falciparum malaria.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001119.
Information is available from WHO on malaria (in several languages); the 2010 World Malaria Report provides details of the current global malaria situation; the WHO Guidelines for the Treatment of Malaria and the report Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Malaria are available
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including a selection of personal stories about malaria
Information is available from the Roll Back Malaria Partnership on the global control of malaria including fact sheets about ACTs and about malaria in Africa
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1001119
PMCID: PMC3210754  PMID: 22087077

Results 1-25 (992213)