Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas ISSN: 0717-7917 [email protected] Universidad de Santiago de Chile Chile

O. Ojewole, John A. Indigenous plants and schistosomiasis control in south africa:molluscicidal activity of some zulu medicinal plants Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, vol. 3, núm. 1, enero, 2004, pp. 8-22 Universidad de Santiago de Chile Santiago, Chile

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3. Harnischfeger, G. Proposed guidelines for commercial collection of medicinal plant material. INDIGENOUS PLANTS AND Journal of Herbs, Spices & Medicinal Plants. SCHISTOSOMIASIS CONTROL IN SOUTH 2000; 7: 43-50. AFRICA : MOLLUSCICIDAL ACTIVITY OF 4. WHO. 1991. Guidelines for the assessment of SOME ZULU MEDICINAL PLANTS herbal medicines. Programme on Traditional Medicine. Document WHO / TRM/ 91.4. JOHN A. O. OJEWOLE9

Received: Febreary 8, 2003 FRASES Received with correction: April 25, 2003 Accepted: Jyly 15, 2003 Ninguno puede ser feliz si no se aprecia a sí mismo ABSTRACT: This work reviews plant molluscicides and presents preliminary findings of a molluscicidal Jean Jacques Rousseau screening programme carried out on some South African candidate molluscicidal plants. The overall Aunque nadie justifique el desvarío, atrévete; objective of studies on plant molluscicides is to Aunque el mundo te tilde de idealista, lánzate; complement methods for controlling snails acting as Aunque sean ilusiones vanas, muéstralas; intermediate hosts of schistosomes. In the last two Aunque ya no se use la poesía, ¡vívela! decades, plant molluscicides have received

5 considerable attention in the search for cheaper, Anónimo effective, environmentally-friendly alternatives to expensive, imported chemotherapeutic agents and La fama es la amada de todo corazón humano synthetic molluscicides used in schistosomiasis control. Although molluscicidal screening Charles Dickens programmes have been conducted in many African countries, only relatively little efforts have been made Excusarse antes de ocasión es culparse to identify South African plants which could be suitable for use locally as plant molluascicides. The Baltasar Gracián attraction of a locally grown molluscicidal plant is based on the development of a philosophy of self- El valor, la buena conducta y la reliance and community participation. This approach perseverancia conquistan a todo lo que se les is dependent on community recognition of the pone por delante infection as a public health menace, and their

6 acceptance of the proposed control measures. Anónimo Schistosomiasis has been recognized as a primary health problem in KwaZulu-Natal Province of South Perdedor no es quien llega último sino quien Africa, especially among the people in the rural no se atreve a competir communities that depend on river-water for all their

7 water requirements. Concerns for schistosomiasis in Anónimo the Province have indeed been matched by a 75% prevalence of haematobium infection Una cosa es continuar la historia y otra repetirla among children aged 6 to 16 years. Forty-one medicinal plants commonly used by traditional Jacinto Benavente healers for the treatment of schistosomiasis in KwaZulu-Natal Province of South Africa were Nunca discutas con un tonto, la gente puede no evaluated for molluscicidal activity according to notar la diferencia

8 Ley de Murphy 8 Contribución de Gabriela Ricciardi, Universidad Nacional del Nordeste; Corrientes; Argentina

5 Contribución de Gabriela Ricciardi, Universidad 9 Department of Pharmacology, Faculty of Health Nacional del Nordeste; Corrientes; Argentina Sciences, University of Durban-Westville, Private 6 Contribución de Dr. Marco A. Montes, Concepción, Bag X54001, Durban 4000, SOUTH AFRICA. Chile. Author’s Contact Numbers: 7 Contribución de Gabriela Ricciardi, Universidad Tel. +27 – 31 – 204 – 4356 Nacional del Nordeste; Corrientes; Argentina Fax +27 – 31 – 204 – 4907 E-Mail: [email protected] BLACPMA Vol. 3 Nº 1 – Enero 2004 9

WHO’s method, using niclosamide (Bayluscide) as molluascicidales. El interes por una planta con esta reference molluscicide for comparison. Adult actividad a nivel local, esta basado en el desarrollo africanus and Biomphalaria pfeifferi were exposed to de una filosofía de máxima confianza y la sublethal and lethal doses of crude, aqueous extracts participación de la comunidad. Este acercamiento es of the Zulu antischistosomal plants for a period of 24 dependiente en el reconocimiento de la comunidad hours. Results obtained indicate that 14 (34%) of the de la infección como una amenaza de salud pública, 41 plants examined possess moderate to strong y su aceptación de las medidas de control molluscicidal properties. Sublethal, toxic effects of the propuestas. Schistosomiasis se ha reconocido como active plant extracts on the snails included retraction un problema de salud primario en la Provincia of the foot-sole and mobility, swelling of the KwaZulu-Natal de Sudafrica, sobre todo entre las cephalopedal mass, and haemorrhagic blistering in personas en las comunidades rurales que dependen the subepithelium of the foot-sole, while del agua del río para todas sus necesidades. Las administration of lethal doses resulted in cessation of preocupaciones para el schistosomiasis en la mobility, severe swelling of the cephalopedal mass, Provincia han sido analizadas debido a un increased mucous secretion, and haemorrhage. It is prodominio de un 75% de infección por Schistosoma speculated that part of the molluscicidal actions of the haematobium entre los niños de edades entre 6 a 16 active plant extracts could involve distruption of the años. Se evaluaron 41 plantas medicinales snails’ foot-sole epithelium osmoregulatory normalmente usadas por los sanadores tradicionales physiology and enzyme-mediated pathways. para el tratamiento de schistosomiasis en la However, osmolality and electrolyte studies, as well Provincia KwaZulu-Natal de Sudafrica para la as enzymatic, histochemical and biochemical studies actividad molluscicidal según el Método de la OMS, are required to substantiate these possible modes of mientras que usando el fármaco niclosamide molluscicidal action of the South African candidate (Bayluscide como el molluscicida de referencia para plant molluscicides. Treatment of schistosomiasis is hacer la comparación. adulto y based on chemotherapy with praziquantel, which is Biomphalaria pfeifferi fueron expuestos a dosis the currently-available drug of choice for all forms of subletal y letales de extractos crudos, ácuosos de las the disease. However, since resistance to plantas de antischistosomal Zulús para un período de praziquantel has been demonstrated in many 24 horas. Los resultados obtenidos indican que 14 schistosomiasis endemic areas of the world; of (34%) de las 41 plantas examinadas posee una necessity is a holistic approach which should include propiedad moderada a las actividad molluscicidal. not only reducing the disease burden in Dosis subletal, los efectos tóxicos de los extractos schistosomiasis-infected persons, but also measures activos de la planta medicinal en los caracoles interfering with the life-cycle of the parasite by incluyeron retractación y movilidad de la del cuerpo eliminating the intermediate host snail vectors. del caracol, mientras la masa cefalopedal se inflamo, Inexpensive, non-toxic, effective and readily-available y produjo coagulos hemorragicos en el subepitelio alternative drugs from natural sources are certainly del cuerpo del caracol, mientras la administración de warranted. dosis letales producía la cesación de movilidad, la KEY WORDS: Schistosomiasis; Molluscicidal Plants; hinchazón severa de la base ventral del cuerpo, Snail Control; Molluscicide; Niclosamide. secreción mucosa aumentada, y hemorragia. Se especula que parte de las acciones molluscicidal de RESUMEN: Este trabajo revisa las plantas los extractos activos pudiera involucrar disrupción del medicinales molluscicidales y presenta resultados epitelio del cuerpo del caracol, de la fisiología preliminares de los analisis de esta actividad del osmoregulatoria de la zona epitelial del cuerpo del programa llevado a cabo con algunas plantas de caracol y sendas enzima-mediadas. Sin embargo, el Sudafrica. El objetivo global de los estudios en estas estudio de osmolaridad y del electrólito, así como plantas es complementar los métodos para controlar enzimático, exigen histoquimicamente los estudios caracoles que actúan como los organizadores bioquímicos para probar estos posibles modos de intermediarios de schistosomas. Las plantas han acción molluscicidales de las plantas medicinales recibido una atención considerable en la búsqueda estudiadas en Sudafrica. El tratamiento de de alternativas más baratas, eficaces, medio schistosomiasis es basado en la quimioterapia con ambientalmente-amistosas para los agentes praziquantel que es la droga actualmente-disponible quimioterapéuticos caros, importados y los de opción para todos los formularios de la molluscicides sintéticos usados en el control de la enfermedad. Sin embargo, desde la resistencia al schistosomiasis en las últimas dos décadas. Aunque praziquantel se ha demostrado en muchos los analisis molluscicidales de los programas han schistosomiasis, las áreas endémicas del mundo; por sido conducidos en muchos países africanos, han necesidad es un acercamiento holístico que debe sido sólo esfuerzos relativamente pequeños para incluir no sólo reduciendo la carga de la enfermedad identificar plantas Sudafricanas que podrían ser en las personas schistosomiasis-infectadas, pero localmente conveniente para el uso como plantas también medidas que interfieren con el ciclo de vida BLACPMA Vol. 3 Nº 1 – Enero 2004 10 del parásito eliminando los intermediarios como el deposited into fresh water, it hatches within a few vector caracol. Barato, no-tóxico, se garantizan minutes to a miracidium, a highly motile larva which drogas de alternativa eficaces y prontamente- moves about in the water for about 24 hours with the disponibles de las fuentes naturales ciertamente. aid of its cilia. It then seeks a suitable snail host. Once inside the soft tissues of a favourable snail INTRODUCTION host, the miracidium develops within 96 hours into a sporocyst. After 7 days, the sporocyst develops into Schistosomiasis (sometimes called “bilharziasis”) is cercaria, the final larval form. The cycle from snail frequently referred to as the second most important penetration by the miracidium to the production of parasitic disease after malaria among the infectious mature cercaria takes about 4 to 5 weeks for S. diseases of tropical and subtropical countries, and mansoni; 5 to 6 weeks for S. haematobium; and 7 the third most prevalent parasitic disease in the world weeks or more for S. japonicum. The infected snails in terms of overall morbidity burden, socio-economic are damaged in the process, and they die shortly and public health importance, and human impact. It after releasing the cercariae into water. The mature has been estimated that more than 200 million cercaria escapes from the daughter sporocyst and people in rural, agricultural and peri-urban areas of enters the water, swimming vigorously by means of 74 tropical and subtropical countries of the world are its bifurcated tail. A snail can shed 500 – 3000 infected with schistosomiasis, of whom 120 million cercariae of S. haematobium or S. mansoni daily are symptomatic and 20 million suffer severe when in full production, but the figure for S. consequences of the disease. An estimated 600 japonicum is much less (15 – 160), the snails being million other people are reported to be at risk of this much smaller than those infected by the other nematode disease. In many countries, species. Cercariae do not feed and their life-span is o schistosomiasis affects a large proportion of under-17 short, up to 48 hours. They are quickly killed at 50 C children. For the control of the disease, a multi- and strong sunlight, and lack of oxygen is also lethal faceted approach is desirable, including control of the to them. A cercaria can penetrate the skin of a intermediate host snails. definitive host within a few minutes. In doing so it Schistosomiasis is a parasitic disease caused by sheds its tail, and once in the definitive host’s tissues, digenean blood trematodes of the genus it becomes a Schistosomulum. Within 24 hours, the Schistosoma. Biologically, the flukes belong to the schistosomulum enters the lymphatic or venous Phylum: Platyhelminthes; Class: Trematoda; system of the host to be transported to the right Subclass: ; Family: ; and heart and lungs. Some schistosomules pass into the Genus: Schistosoma. The five most common species mesenteric vessels and thence to the vessels of the of schistosomes infecting man and causing human liver. Some may pass directly through the diaphragm schistosomiasis are: (i) Schistisoma haematobium to the liver and the portal vessels. Growth takes place (which affects 54 countries in Africa and the Eastern in the liver, and paired worms may be found after Mediterranean, and causes urinary schistosomiasis), about 26 days following host skin’s penetration. Most (ii) (which is responsible for worms leave the liver when they are sexually mature African intestinal schistosomiasis), (iii) Schistosoma and have mated, and migrate to the veins of the japonicum, (iv) Schistosoma mekongi (the two vesical plexus (S. haematobium) or the mesenteric schistosomal species that cause intestinal veins (S. mansoni, S. japonicum and S. intercalatum), schistosomiasis in Asia and the Pacific regions), and where they begin to lay eggs. The period between (v) . Other species of skin penetration by the cercariae and egg-laying may Schistosoma which parasitize man and other be 30 – 40 days or more. The mated worms move as mammals are Schistosoma mattheei and far as possible towards the fine terminal vessels, and Schistosoma bovis. Like other digenetic trematodes, the female worm then leaves the male, moving to the the schistosomes are equipped with suckers with finest vessels, where she deposits her eggs, which the worms attach themselves to the walls of retracting after having done so. The eggs escape the blood vessels in which they live. from the venules into the host’s tissues, those of S. The life-cycle of the trematodes that cause haematobium largely into the wall of the bladder but schistosomiasis in man is atypical of the other occasionally into the wall of the lower bowel, those of parasites of the Class Trematoda in that the worms S. mansoni, S. japonicum and S. intercalatum mainly are unisexual. Adult worms in humans reside in the into the wall of the lower bowel. Only about 50% of mesenteric venules in various locations, which at the eggs produced by the adult worms are passed times seem to be specific for each species. For out in the urine or stool. The remaining half (50%) instance, Schistosoma haematobium normally lives stay in the body where they can scar and damage and mates in the veins of the urinary bladder of man vital organs. The symptoms of the disease are (the only important definitive host), producing eggs caused by the body’s reaction to the worms’ eggs, with a terminal spine, which pass into the bladder and not by the worms themselves. Microscopic wall and thence into the urine. When an egg is identification of schistosomal eggs in the stool or BLACPMA Vol. 3 Nº 1 – Enero 2004 11 urine of patients is the most practical method for the infection by miracidia from those eggs, and capable diagnosis of schistosomiasis. Stool examination of producing cercariae infective to man. Water should be performed when infection with S. mansoni temperature, rate of flow, acidity or alkalinity, and or S. japonicum is suspected, and urine examination content of organic matter conducive to snail growth should be performed if S. haematobium is suspected. are also important. Furthermore, human contact with In addition to microscopy, ‘antibody detection’ can be water containing living cercariae by bathing, wading, used in the clinical management of recent infections washing, swimming in, or drinking it is a crucial factor. and for epidemiological surveys. Some eggs of all Infection is strongly influenced by social and religious Schistosoma species are also usually found in the practices in relation to contact with water. genital tract, liver, lungs, central nervous system, and Schistosomiasis has a long history. As early as 1050 other organs. The eggs are generally responsible for BC, Egyptian pharaohs wrote about urinary bladder the pathological effects of the disease, the symptoms disturbances. Schistosomal ova were found in the of which depend upon the intensity of infection. The cirrhotic liver of an Egyptian mummy around 1200 pathological stage may last for a long time, BC. Historically, it was generally thought that the old culminating in irreversible effects if not treated. In papyrus records from Egypt indicate that Schistosoma haematobium, the urinary system bears schistosomiasis (bilharziasis) was common around the heaviest pathological burden, and the symptoms 2000 BC with the hieroglyph for the widely spread vary greatly. In the early stages, there is often slight “aaa disease” being interpreted as “haematuria”. fever, with general weakness and prostration, but the Egypt was the centre for much of the early work on most characteristic sign is haematuria with or without schistosomiasis. The disease was certainly endemic a sense of urinary irritation or pain. Systemic there in ancient times, but there are now doubts as to complications with evidence of hepatocellular the veracity of the traditional interpretation of damage, cough, myalgia, abdominal pain, skin rash, hieroglyphs in Egyptian papyri and paintings thought and so on, have been reported. to mean haematuria, its treatment and prevention. Schistosoma mansoni normally lives and mates in the However, epidemiological studies on schistosomiasis superior mesenteric veins of man, producing eggs began in the middle of the 19th century both in Egypt with a lateral spine which pass into the wall of the and Japan. ‘Asiatic schistosomiasis’, as it later large intestine and lower ileum, and thence into the became known, was described from Katayama in faeces. Schistosoma japonicum normally lives and Japan in 1847. The original description of ‘Asiatic mates in the inferior mesenteric veins of man, schistosomiasis’ was given by Fujii in 1847. Pruritic producing eggs which pass into the bowel wall and papules on the legs of persons working in flooded thence into the faeces. Although Schistosoma rice fields constitute the dominant feature of the haematobium most often occurs in the venus plexus disease that affected all age groups. Abdominal of the bladder, it can also be found in the rectal upsets were common, and when symptoms venules. The female worms of the parasites (size 7 – continued, the typical stages of what we now know as 20 mm) deposit eggs in the intestinal or bladder small ‘hepatosplenic schistosomiasis’ developed – and venules. Schistosoma intercalatum is a parasite of there was no effective treatment. According to the S. haematobium complex, producing legend, the disease started after a ship sank near characteristic eggs with a terminal spine, but found Kata Mountain (Katayama) in a bay that was exclusively in faeces. It lives and mates in the eventually reclaimed from the sea (1). What became mesenteric-portal venous system. The eggs of known as ‘Katayama disease’ was later recognized in Schistosoma mattheei, a parasite of sheep and cattle other parts of Japan, and studied independently in which affects man in South Africa, is also found in each locality of the country. The causative parasite, both urine and faeces. Schistosoma japonicum, was not identified until early Strains of schistosoma spp. which infect man vary 20th century, but unraveling the life-cycle of the fluke widely in their ability to infect passive intermediate took only a few years, being aided by the use of snail hosts. Some schistosomes readily infect snails domestic as alternative hosts to man, in of one geographical area and not of the other. transmission experiments. Schistosoma haematobium is transmitted by snails of Theodore Bilharz [1825 – 1862], a German scientist, the genus Bulinus, while Schistosoma mansoni is pathologist and medical doctor, identified the cause transmitted by snails of the genus Biomphalaria. of ‘African schistosomiasis’ at Kasr El-Eini Hospital in While snails of Oncomelania spp. transmit Cairo in 1852 (2, 3). However, the transmission Schistosoma japonicum, snails of Lythoglyphopsis picture in ‘African schistosomiasis’ was complicated spp. transmit Schistosoma mekongi. by the fact that two species of worms were involved, Schistosomiasis in all its forms, is a rural disease, each using a different genus of snail intermediate and depends on a variety of other factors. These host, but apparently without alternative hosts to man. factors include contamination of fresh water with Between 1851 and 1853, in a series of autopsies, human urine or faeces containing schistosomal eggs; Bilharz found trematode blood flukes with separate the presence in the water of snails capable of male and female adult worms, in the bladder wall and BLACPMA Vol. 3 Nº 1 – Enero 2004 12 in the mesenteric veins. Bilharz noted that the female include: colonic polyposis with bloody diarrhoea worms from the bladder wall contained an abundance (Schistosoma mansoni mostly); portal hypertension of eggs compared with those from the mesenteric with haematemesis and splenomegaly (Schistosoma veins. Although Bilharz had partly solved the problem mansoni, S. japonicum); cystitis and urethritis with of the disease that was to subsequently bear his haematuria (S. haematobium) which can progress to name ± he had at least identified the cause ± the bladder cancer; pulmonary hypertension (S. mansoni, failure to incriminate the two species of worm laid the S. japonicum, and more rarely, S. haematobium); foundations for a future scientific controversy that glomerulonephritis; and central nervous system was to make and break reputations half a century lesions. Within few to several weeks, worms grow later (1). inside the blood vessels of the infected person/s, and The life-cycle of the parasites remained a mystery for the adult female worms produce eggs. Some of these more than 60 years, during which time numerous eggs travel to the bladder or intestines, and are preparations from the pharmacopoeia of the day passed out of the body with urine or stool. were tried in the search for a cure. Leiper (4,5), an The socio-economic and health effects of English scientist, and Leiper and Atkinson (6) schistosomiasis cannot be underestimated. School discovered the intermediate snail hosts for S. performance and growth patterns of infected children haematobium and S. mansoni. At about the time that are retarded, although the effects are 90% reversible Leiper discovered the life-cycle of Schistosoma on average with treatment. In Egypt, Sudan and haematobium, confirmed the existence of the long North-East Brazil, the work capacity of rural suspected Schistosoma mansoni and discovered its inhabitants is severely reduced due to weakness and life-cycle, a highly effective treatment, antimony lethargy caused by the disease. Urinary potassium tartrate (or tartar emetic), was found. schistosomiasis causes a specific type of bladder Tartar emetic brought hope where there had been cancer, and it has been established that in some none, and laid the foundations for rational control of parts of Africa, the incidence of bladder cancer linked the disease (1). In Sudan, it was used in a preventive with schistosomiasis is 32 times higher than that of control programme to stop bilharziasis invading the simple bladder cancer in the USA and Europe (7). Gezira Irrigation Scheme, and in Egypt, it was used for morbidity control. Combined with mollusciciding, Despite more than half a century of international tartar emetic provided the means for the first research on schistosomiasis control, this disease is transmission control study which took place in Dakhla still a public health menace in many developing Oasis (1). Hopes that the disease could be controlled countries, especially in Africa, Asia and South easily faded rapidly, and it must be admitted that America. Chemotherapy and transmission reduction even if we now have a better understanding of what via intermediate host snail eradication are the two is required for control in different epidemiological main tools in the control of schistosomiasis. Control situations, effective implementation is still often a of the intermediate snail host is still considered the problem. most important means of schistosomiasis control Schistosomes that cause human schistosomiasis where the water volume per head of human enter the body through skin contact with infected population at risk of infection is small (8). However, fresh water in which snails that carry the safe and effective drugs are now available for the schistosomes live. This occurs mainly among people treatment of schistosomiasis. Schistosomicides such who drink the water or use it for washing, bathing, as antimonials were introduced as the drugs of swimming or work activities such as fishing, rice choice, and they continued to be used as such until cultivation, or irrigation. However, rural±urban the early 1960s. The antimonials were administered migration is also introducing the disease into peri- intravenously. However, the severe side-effects of the urban areas in Africa and North-East Brazil, while antimonials made their application difficult and refugee movements are spreading the disease in adversely affected their use in large-scale Somalia and Cambodia. More tourists are now chemotherapy campaign. The antimonials were, contracting schistosomiasis with the rise in ªoff-trackº therefore, replaced by hycanthone and lucanthone tourism, at times with severe acute infection and which were administered intramuscularly. These unusual sequelae including paralysis of the legs (1). drugs produced side-effects such as hepatotoxicity Although many infections are asymptomatic, acute and gastrointestinal disturbances, and were schistosomiasis (ªKatayama feverº) may occur a few consequently withdrawn. It was then decided that the weeks after the initial infection, especially by S. alternative was to produce synthetic drugs that could mansoni and S. japonicum. Manifestations of acute be administered orally. Niridazole, oxamniquine and schistosomiasis include fever, cough, abdominal metrifonate were consequently introduced as pain, diarrhoea, hepato-splenomegaly, itching and schistosomicidal agents, while drugs like oltipraz and eosinophilia. Continuing infection may cause amoscanate were still at clinical trial phase. granulomatous reactions and fibrosis in the affected Therapeutic doses of drugs like hycanthone, organs, which may result in manifestations that niridazole and amoscanate were found to cause BLACPMA Vol. 3 Nº 1 – Enero 2004 13 many major side-effects and were, therefore, However, this synthetic molluscicide tends to be considered unsafe. generally biocidal, toxic to fish and microscopic The introduction of relatively safe, effective, broad- aquatic animals, and affecting many of the plants in spectrum oral antheminthic agent, praziquantel, the snail habitat. Furthermore, the compound is often constituted a significant landmark in the not affordable and/or available in many of the poor, chemotherapeutic control of schistosomiasis. To schistosomiasis-endemic countries. The rising cost of date, praziquantel is the drug of choice for infections proprietary molluscicides has stimulated a search for caused by all species of Schistosoma. Oxamniquine cheaper, natural compounds from plants. This has also been used effectively in treating infections strategy relies on the integration of snail control into caused by S. mansoni in some cases where the activities of self-help schemes and projects in praziquantel is less effective. Studies have also rural areas. Moreover, the use of indigenous rather shown that metrifonate is as effective as praziquantel than imported materials is desirable, especially as in treating S. haematobium and S. mansoni strategies for schistosomiasis control programmes infections. Because praziquantel is effective even in should be based on long-term operations (6). treating advanced hepatosplenic schistosomiasis, Although chemotherapy is one of the most valuable with fewer side-effects, the drug is currently the drug methods of controlling schistosomiasis, there is a of choice for the treatment of any kind of pressing need for more selective and effective schistosomiasis. Its only limitation is the cost which molluscicides for the control of snail vectors. Many restricts its use in many developing countries. With plants have been screened for their intrinsic the introduction of praziquantel, there has been a molluscicidal properties in an attempt to find an shift away from transmission control to the control of affordable alternative to niclosamide. However, severe morbidity. However, despite the effectiveness despite the discovery of several promising plant of praziquantel, there is a high re-infectivity rate in molluscicides, none of them has yet been used in endemic areas even after mass treatment. Repeated schistosomiasis control campaigns. Plants with treatment will, therefore, be necessary, although it molluscicidal activity may be exploited to contribute to has not been established what would be a suitable schistosomiasis contol, especially if they are already interval between such treatments. Furthermore, the grown locally for other purposes. The use of plants cost of praziquantel remains prohibitive for mass with molluscicidal properties is a simple, inexpensive control programmes in many schistosomiasis and appropriate technology for the snail control. endemic areas of the world. Together with Since the discovery of active saponins in the berries chemotherapy, molluscicides are widely considered of Phytolacca dodecandra (L'Herit), naturally to be an important tool of schistosomiasis control that occurring molluscicides are receiving considerable can be used at selected transmission sites to achieve attention. quick results. Measures such as improved sanitation During the last few decades, plant molluscicides have and health education are likely to take longer time to received considerable attention in the search for affect the disease spread and prevalence. cheaper alternatives to existing chemotherapeutic While effective and safe drugs for schistosomiasis agents and synthetic molluscicides in schistosomiasis mass chemotherapy campaign are being developed, control. On the African continent, interest in plant problems of therapeutic failure and drug resistance molluscicides dates from the 1930s when Archibald are being reported in some developing countries of (1933) (11) and Wager (1936) (12) advocated the world. Under these circumstances, alternative planting of the desert palm, Balanites aegyptiaca and drugs must be found. Mass treatment, a crucial goal B. maughamii, along the water courses of Sudan and in the eventual control of schistosomiasis, awaits a South Africa, respectively. The laboratory and field well-tolerated and non-toxic drug that will ultimately trials of the two latter scientists indicated that the fruit prove to be effective where and when cure is definite of the plants which fell into the water prevented and non-negotiable. However, treatment of this subsequent increase in snail population density. preventable disease must always be accompanied by These encouraging findings prompted the good health education and hygiene practices. introduction of Balanites aegyptiaca to Puerto Rico, Treatment of schistosomiasis is now simple, and where it was planted around Biomphalaria glabrata- control of the disease can protect millions of people infested pools with apparently beneficial results. in schistosomiasis-endemic areas of the world, Mozley (1939) (13) considered B. aegyptiaca and two especially in Africa, South America, China and Asia. other saponin-containing plants, Sapindus saponaria, Reducing the intensity of infection can ultimately the berries of which were widely used in Africa and reduce morbidity and mortality. For the control of South America as a fish poison and soap, and schistosomiasis, multi-faceted approaches are Swartzia madagascariensis, a traditional African desirable, including control of the intermediate host medicine and fish poison (12), to be among the most snails. At present, niclosamide (Bayluscide, Bayer, promising vegetable molluscicides. Using the berries Germany) is the only commercially-available of S. saponaria, Mozley (1939) (13) controlled a molluscicide applied on a large scale (9, 10). population of Bulinus africanus in a pond in Zanzibar BLACPMA Vol. 3 Nº 1 – Enero 2004 14

(6). In South America, preliminary studies by other species exhibited great variations in potencies, Luttermoser (1946) in Venezuela, and by Pinto and and highest toxicity levels were most often found in Almeida (1944) (14) in Brazil, showed that the berries the flowers and leaves. Several species of Solanum of S. saponaria were lethal to numerous microscopic are being cultivated for solasodine, a sapogenin used aquatic organisms, as well as to the host snails of in the production of pharmaceutical steroids. Schistosoma and Fasciola. Synergistic effects were Solasodine, and possibly solamargine, another found between the extracts of S. saponaria and glycoalkaloid in the fruit of Solanum mammosum, sodium pentachlorophenate. For many years that were significantly more toxic than the crude aqueous followed, neither of the plants, nor any of the several and methanolic extracts (Alzerreca et al., 1981) (23). other `Old World' fish poisons, was further exploited Although the small number of plant species tested by for the control of snail vectors. Indeed, not until the Medina and Woodbury (1979) (22) did not permit mid-1960s was the first plant, Phytolacca detailed comparisons between plant families, it was dodecandra, used for the control of schistosomiasis noted that the greatest proportion of molluscicidal in an endemic focus in Ethiopia (15). plants found are from the families: Solanaceae, Encouraged and stimulated by these early studies, Phytolaccaceae, Fabaceae, Rubiaceae, and the search for plants with molluscicidal potential was Euphorbiaceae. The toxicity of the two Phytolacca intensified as exemplified by the extensive screening species tested against Lymnaea spp. corroborates and general improvement of screening methods and the findings of several other investigators (24). The techniques reported by various investigators most extensive plant screening programme has been worldwide (7). Amorin and Pessoa (1962) (16) carried out in China, where nearly 600 indigenous randomly screened fresh materials of nine plants plants have been tested for snail toxicity. Less than indigenous to Alagoas State of Brazil. Three of the 20 species were mildly toxic at concentrations of 10 plnts, Paullinia pinnata, Stenolobium velutinum and 000 ppm and lower. No plant species has thus been Piptadenia macrocarpa, were found to be only mildly considered to be cost-effective for large-scale use molluscicidal at 1000 ppm, probably due to the fresh (25). and green states of the plants. Silva et al., (1971) Twenty-three of the 181 methanolic extracts (12.7%) (17) screened another 30 species of plants representing 106 plant species used in Nigerian indigenous to Brazil, four of which were toxic to herbal medicine, gave 100% kill against Bulinus Biomphalaria straminea, but only one, Agonandra globosus (26). They include the root of Rauvolfia brasiliensis, was molluscicidal at 100 ppm. Possible caffra, the stem and root of Bombax costatum, the confinement of the active ingredient in the bark, fruit of Dialium guineense, the root and stem of which regenerates slowly, of A. brasiliensis and Combretum spp., and the root of Terminalia mollis, Brysonium sericea probably precludes their practical the root of Cryptogonone argentea, the stem of Acioa use for snail control. The bark of Ziziphus undulata emenii and A. ruatisii, the leaves of Morinda lucida was found to have no effect on the snails, but and Rothmania whitefieldii, the leaves of Xiris Barbosa and Mello (1969) (18) reported 30% anceps, and fruits of Tetrapleura tetraptera. Many mortality in Biomphalaria glabrata exposed to a 10- plant species have undergone systematic field ppm water extract of Z. jaozeiro. In North-East Brazil, evaluation in other endemic areas of Africa. The most several studies have implicated many plants as notable work has been carried out in Ethiopia on potential molluscicides. However, fish and many Phytolacca dodecandra. Other plant species being other aquatic organisms succumbed to lower tested include: Ambrosia maritime (Egypt); concentrations of the plant extracts than those Anacardium occidentale (Mozambique); Swartzia required to kill the snails, and resistance of the plants madagascariensis (Tanzania); Croton machrostachys to physio-chemical stress (sunlight, temperature and Jatropha curcas (Sudan) (7, 27, 28); and variations, silt, pH, etc) remains to be studied before Vernonia amygdalina, Terminalia brachystemma, their suitability as plant molluscicides can be fully Ricinus communis, Maytenus senegalensis, Abrus assessed (7). precatorius, Pterocarpus angolensis, Securidaca As natural pesticides, plants have long held the longipedunculata, Ozoroa insignis, Dicoma anomala, interest of biologists wanting to control diseases such Ximenia caffra, Lannea edulis, Elephantorrhiza as schistosomiasis, fascioliasis, malaria, filariasis and goetzei (Zimbabwe) (29). dengue (19, 20, 21). Medina and Woodbury (1979) In South Africa, most rural and informal settlements (22) tested all parts of 198 plants indigenous to rely heavily on natural water bodies for their domestic Puerto Rico and two to the Dominican Republic. and recreational needs, and consequently, Water extracts of 30 species of the plants were found schistosomiasis is a major health problem in the to be lethal to Lymnaea cubensis and L. columnella country. Schistosomiasis is mainly endemic in, and at 1000 ppm. For further screening, the plant restricted to, the eastern and northern regions of the products were oven-dried and tested as water country, namely: Mpumalanga, KwaZulu-Natal and extracts at 25, 100 and 1000 ppm. Hedychium Northern (Limpopo) Provinces. In these provinces, coronarium yielded the most potent extract, while infection is characteristically associated with an BLACPMA Vol. 3 Nº 1 – Enero 2004 15 absence of pipe-borne water, good recreation and because these intrinsic elements influence their sanitary facilities (28, 30). health and determine their involvement in any It has been estimated that at least 40% of the school intervention programme (40). Reports of research children in KwaZulu-Natal Province of South Africa findings on plant molluscicides from various countries are afflicted with schistosomiasis. Stopforth (1976) of Africa, Latin America, Asia and other parts of the (31) recorded that 47 families at Adams Mission in world have permeated the medical literature. To date, KwaZulu-Natal considered schistosomiasis to be the however, only a few of such research reports have most important childhood illness prevailing among been documented for South African plant children between 6 and 16 years old. The foci of molluscicides. The core aim of the present study was endemic areas are, therefore, expected to be in rural to screen for molluscicidal activity, some of the South areas. Generally, a national anti-schistosomiasis African medicinal plants commonly used in Zulu folk control programme has never operated in South medicine for treating schistosomal infections and Africa, and there is no National Control Programme to controlling intermediate snail hosts of fund or initiate any control measures in the country. schistosomiasis. There is a high prevalence of the disease amongst the populace, especially among the children (32). MATERIALS AND METHODS Despite records in excess of 70% for large areas of the endemic region (28, 33, 34), schistosomiasis is PLANT MATERIAL: The plants examined in this not a notifiable disease in South Africa. Under these study were selected on the basis of circumstances, of necessity is a holistic approach ethnopharmacological information indicating their which should include not only chemotherapeutic medicinal uses in schistosomiasis control in endemic measures, but also measures interfering with the life- areas of KwaZulu-Natal Province of South Africa. cycle of the parasite by eliminating the intermediate Voucher specimens of the plants are kept at the host vector snails. The only commonly available Natal Provincial Herbarium in Durban. The plant synthetic molluscicide, niclosamide, is too expensive species were collected locally from their natural for most developing countries [including South habitat and identified (with reference to herbarium Africa], which also experience transport, specimens) by the Taxonomist/Curator of the infrastructural and logistical problems in supplying Department of Botany, University of Durban- molluscicides to remote areas and the necessary Westville, Durban 4000, South Africa. The plant expertise to apply them (32). Therefore, there is a materials were sorted out into roots, stems, leaves, need to search for cost-effective alternatives from flowers, fruits and seeds, and shade-dried at room plant sources which can be simply prepared and temperature. applied safely by rural community members themselves. In Southern Africa, research into plant molluscicides have received considerable attention in PREPARATION OF PLANT EXTRACTS: One the last two decades (28). The emphasis has been kilogramme (1 kg) each of the air-dried plant on the identification of cheap, effective and materials used (leaves, root- or stem-barks, fruits, environmentally-acceptable plant products. This is and so on) was ground into fine particles with a particularly true for Africa where adoption of the Waring blender, and Soxhlet extracted twice, on each Western Health Care System has resulted in an occasion with 2.5 litres of distilled water at room expensive, hospital-based, doctor-dependent, urban- temperature for 24 hours with shaking. The combined biased health care system, which is economically aqueous extracts were filtered, concentrated to dryness in vacuo under reduced pressure in a rotary beyond the reach of the rural people (35). The o attraction of the use of indigenous molluscicidal evaporator at 30 ± 1 C and freeze-dried, finally plants lies not only in economic benefit, but also in yielding powdery, crude aqueous extracts of the plant the development of a philosophy of self-reliance in materials. Aliquot portions of the plant extract rural communities (28, 36). Plant material would be residues were weighed and dissolved in distilled cultivated, harvested, processed and applied focally water for use on each day of our molluscicidal to human water contact points, using an appropriate screening tests. From the crude extracts, stock form of technology (29). This is not an unrealistic solutions of concentration series in gram per litre of goal, and indeed many plant species have undergone water (1000 mg/l) were freshly prepared in distilled systematic field evaluation for snail vector control in water. Different test dilute solutions, ranging from 10 other endemic parts of Africa. The success of such to 1000 mg/l, (i.e., ppm) were prepared from the self-help programmes is, however, dependent on the stock solutions, using deionized and dechlorinated support of the affected communities. Community water, to determine the LD50 and LD90 values. willingness to participate, in turn, presupposes recognition of infection and its economic burden and TEST SNAILS: Species of intermediate snail hosts of effects as a public health problem (28, 37, 38, 39). urinary and intestinal schistosomiasis in KwaZulu- The study of community beliefs and habits is vital Natal Province of South Africa, Bulinus africanus and BLACPMA Vol. 3 Nº 1 – Enero 2004 16

Biomphalaria pfeifferi, were used in this study. Adult to the foot-sole, the snail immediately retracted into snails were collected from ponds and water courses its shell. In the test snails, the toxic effects of the in Randle Park, Overport in Durban, KwaZulu-Natal active plant extracts became evident. There was Province. The ponds had not been previously treated either a partial retraction (withdrawal response) in the with molluscicides. Uninfected snails, that is, those partially dead snails, or no retraction at all (in the that did not show patent trematode infections, were dead snails) to mechanical stimulation of the foot- acclimatized in pond water to laboratory conditions sole with a blunt needle. There was a visible swelling for seven days before being used in our molluscicidal of the cephalopedal mass. Development of tests. Ten snails were then allocated to each of the haemorrhagic `blisters' over the ventral surface of the groups and immersed in either untreated, foot-sole was also noted. High doses of the active dechlorinated tap water (control) or aqueous extract- plant extracts caused the cephalopedal mass of each treated dechlorinated water. Preparations of the plant snail to become severely swollen, turgid and failing to extracts and toxicity test protocols were adapted from respond to mechanical stimulation with a blunt those described by Brackenbury and Appleton in needle. Mucus secretion was observed over most of 1997 (18, 19). the foot.

MOLLUSCICIDAL ACTIVITY TESTS: Molluscicidal EXPERIMENTAL FINDINGS: The 41 South African evaluations of the plant extracts were performed candidate molluscicidal plants examined (see Table according to WHO guidelines (WHO, 1965). Groups 1) were claimed by Zulu traditional healers to be of 10 uninfected snails were placed in glass `tanks' useful both as molluscicides in snail vector control (containers) with some sand, snail food and 1000 ml and in the treatment of urinary and intestinal of deionized and dechlorinated pond or tap water schistosomiasis. The plants are primarily used to bubbled with atmospheric air. Tests were carried out treat haematuria caused by Schistosoma at room temperature (26±1oC). In each set-up, the haematobium infection, and/or stomach troubles snails were prevented from crawling out of the glass caused by Schistosoma mansoni infection. The container by means of a fine stainless steel mesh results of our molluscicidal evaluation of the 41 plants placed above the water surface. The test snails were examined are presented in Table 1. challenged with various doses of the plant extracts (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 400, 800 TABLE 1 and 1000 mg/l [ppm]). After 24 hours of exposure to the plant extracts, the snails were transferred to fresh Some South African candidate molluscicidal dechlorinated and deionized water and maintained plants there for another 24 hours. Death of the snails was determined and confirmed by the absence of Parts LD90 heartbeat and lack of reaction to irritation of the foot Family/Genus/ commonly values with a blunt wooden probe to elicit typical withdrawal Species used by for the movements. Control solutions were also made with Traditional snails deionized and dechlorinated tap water. Control Healers used experiments were performed with deionized and Amaranthaceae dechlorinated water alone (`negative control') or with Amaranthus niclosamide [Bayluscide] (`positive control'). 1. spinosus Linn. Aerial 400 ± Molluscicidal test with each plant extract dose was Parts/Leaves 800 separately repeated three times. The snails were ppm neither fed nor disturbed during the exposure and Annonaceae recovery periods. LD50 and LD90 (referring to the plant Annona extract doses in ppm, that kill 50% and 90% of the 2. senegalensis Aerial 100 ± test snails respectively) were determined by the Pers. Parts/Leaves 200 method of Leitchfield and Wilcoxon (1949) (41) with ppm 95% confidence limit. Plant extracts that caused no Apocynaceae mortality at 1000 ppm were considered inactive and Rauvolfia caffra were not investigated further. 3. Sonder Barks/Leaves 200 ± /Twigs 400 RESULTS ppm

BENCHSIDE OBSERVATIONS: Each snail in the Asparagaceae untreated water tanks (controls) initially withdrew into 4. Asparagus Aerial 400 ± its shell, but resumed normal activity after about 45 racemosus Parts/Leaves 800 minutes, moving around the container with its foot Willd. ppm extended. When a mechanical stimulus was applied BLACPMA Vol. 3 Nº 1 – Enero 2004 17

Asteraceae . communis Linn. Seeds 800 Berkheya ppm 5. speciosa (DC) O. Barks/Leaves 50 ± 20 Spirostachys Twigs/Fruits/ 100 ± Hoffm. /Twigs 100 . africana Sond. Seeds 200 ppm ppm Vernonia Fabaceae 6. amygdalina DC. Barks/Leaves 200 ± Acacia nilotica 400 21 (Linn.) Delile Barks/Leaves 100 ± ppm . /Fruits 200 Balanitaceae ppm Balanites 22 Dichrostachys Barks/Leaves 200 ± 7. maughamii Fruits/Leaves 50 ± . cinerea Wight /Fruits 400 Sprague /Barks 100 & Arnott ppm ppm 23 Indigofera Barks/Leaves 100 ± 8. Balanites Fruits/Leaves 50 ± . frutescens /Fruits 200 aegyptiaca /Barks 100 (Linn.) Mill ppm (Linn.) Delile ppm 24 Sesbania Barks/Leaves 200 ± Bignoniaceae . sesban (Linn.) /Fruits 400 Kigelia africana Merr. ppm 9. (Lamk.) Benth Fruits/Seeds 400 ± 25 Tephrosia Barks/Leaves 100 ± 800 . diffusa (Linn.) /Fruits 200 ppm Harv. ppm Icacinaceae Cannellaceae 10 Warburgia Twigs/Leaves 50 ± 26 Apodytes Barks/Leaves 50 ± . salutaris /Fruits 100 . dimidiata E. 100 (Bertol. F.) ppm Meyer ppm Chiov. Ex. Arn. Subsp. 11 Warburgia Twigs/Leaves 50 ± . ugandensis /Fruits 100 dimidiata Sprague ppm Combretaceae Lamiaceae Combretum Leonotis 12 imberbe Wawra Barks/Twigs/ 50 ± 27 leonurus (Linn.) Aerial 400 ± . Leaves 100 . R. BR. Parts/Leaves 800 ppm ppm 13 Combretum Barks/Twigs/ 50 ± Lecythidaceae . molle R. Br. ex Leaves 100 28 Barringtonia Fruits/Seeds 400 ± G. Don ppm . racemosa 800 14 Combretum Barks/Twigs/ 200 ± (Linn.) ppm . fragnans Leaves 400 Roxb. F.Hoffm ppm Meliaceae Ebenaceae Trichilia emetica 15 Euclea Barks/Twigs/ 50 ± 29 Vahl Roots/Leaves 200 ± . natalensis A. Leaves 100 . 400 DC. ppm ppm Euphorbiaceae Olacaceae 16 Euphorbia Twigs/Fruits/ 100 ± 30 Ximenia Barks/Leaves 100 ± . cooperi N.E. Seeds 200 . americana /Fruits 200 Browa ex A. ppm Linn. ppm Berger 31 Ximenia caffra Barks/Leaves 100 ± 17 Euphorbia Twigs/Fruits/ 100 ± . Sond. /Fruits 200 . tirucalli Linn. Seeds 200 ppm ppm Phytolaccaceae 18 Jatropha Twigs/Fruits/ 50 ± 32 Phytolacca Fruits/Leaves 50 ± . curcas Linn. Seeds 100 . dodecandra /Barks 100 ppm Linn. ppm 19 Ricinus Twigs/Fruits/ 400 ± 33 Phytolacca Fruits/Leaves 50 ± . communis Linn. Seeds 800 . octandra Linn. /Barks 100 ppm ppm BLACPMA Vol. 3 Nº 1 – Enero 2004 18

. octandra Linn. /Barks 100 medicine but by African indigenous remedies. ppm Approximately 80% of the Black South Africans 34 Phytolacca Fruits/Leaves 100 ± consult traditional healers as a first resort when ill . americana /Barks 200 (28, 42), and an estimated 75% of the world's Linn. ppm population relies on traditional remedies for their Polygalaceae primary health care needs (28, 43, 44, 45). Home Securidaca remedies and treatment from traditional doctors are 35 longipedunculata Barks/Leaves 400 ± affordable and readily accessible, although there is . Fresen. 800 some doubt as to their success in curing ppm schistosomiasis (28). However, the Zulus of South Rubiaceae Africa do not regard indigenous and Western 36 Gardenia Aerial 50 ± medicine as conflicting. . thunbergia Parts/Leaves 100 The use of plant molluscicides is culturally acceptable Linn. ppm and certainly more accessible than Western 37 Oldenlandia Aerial 200 ± antischistosomal drugs whose availability is limited by . corymbosa Parts/Leaves 400 the cost and transport. The use of plant molluscicides Linn. ppm at community level is imperative, and is in line with Solanaceae the suggestion of Straub and Walzer (1992) (46) that 38 Solanum Aerial 100 ± rural health care needs to step beyond the facility- or . nigrum Linn. Parts/Leaves 200 provider-driven models in search of new solutions. ppm Further evaluation of plant molluscicides and their 39 Solanum Aerial 50 ± potential value in rural South African communities is . nodiflorum Parts/Leaves 100 most certainly warranted (28). The problem that most Jacq. ppm researchers in the field of plant molluscicides 40 Solanum Aerial 100 ± continually encounter in dealing with crude plant . capense Linn. Parts/Leaves 200 extracts is the variability of the secondary metabolite ppm content of the plant material. This variability may 41 Withania Aerial 200 ± arise from a phenoplastic response to environmental . somnifera Linn. Parts/Leaves 400 conditions, and/ or genetic control (32). However, ppm previous studies in our laboratories and elsewhere Positive have shown that potency levels of plant samples vary Control Aqueous significantly according to season and geographical Niclosamide solution 0.20 ± locations of the plants. Such unpredictable trends in  the potency of plant molluscicides militates against (Bayluscide ) 0.8 ppm their selection for control programmes (32). Another important criterion of a molluscicide is that it should

retain its potency during dry storage, preferably for at KEY: least one year (47). This is generally the case for synthetic molluscicides but not so often for plant 0.1 ± 1.0 ppm = Very strong molluscicidal activity products whose shelf-life may vary from four months 50 ± 100 ppm = Moderate to strong molluscicidal to five years (32, 48, 49, 50). Whether or not the plant activity materials examined in this study remain stable for a 100 ± 200 ppm = Mild to moderate molluscicidal period of up to one year or more is not known. activity Storing plant molluscicides in aqueous solutions is 200 ± 400 ppm = Weak to mild molluscicidal activity not a practical consideration due to their rapid loss of 400 ± 800 ppm = Very weak molluscicidal activity potency (32, 48, 49, 50, 51). The stability of such ≥ 1000 ppm = No molluscicidal activity (and solutions could possibly be extended by refrigeration therefore, rejected in this study). (51), but for most rural communities in South Africa, electricity supplies and electrical appliances are Niclosamide (Bayluscide), used as (`positive generally not available or grossly inadequate. control') reference molluscicide, killed all the snails at The results obtained in this study are in consonance a dose of 1 ppm. On the contrary, none of the snails with the findings of earlier investigators from other (in the `negative control') treated with deionized, parts of the world (e.g., 29, 52, 53), and indicate that dechlorinated water alone died. 14 (34%) of the 41 Zulu medicinal plants examined in this study possess moderate to strong molluscicidal DISCUSSION AND CONCLUSION activity (see Table 1). The molluscicidal activity of most of the tested plant extracts is probably due to In Africa, some illnesses are regarded as uniquely the presence of saponins. However, it has been African and, therefore, not treatable by Western established that not only saponins, but also some BLACPMA Vol. 3 Nº 1 – Enero 2004 19 sesquiterpenes, chalcones and flavonol glycosides, molluscicidal properties remain to be discovered. as well as phorbol esters of various plants from Several promising plant molluscicides have been diverse families, possess molluscicidal properties (52, identified. Endod (Phytolacca dodecandra) in 53, 54). particular, compares fairly well with the major After exposure to the active plant extracts examined synthetic molluscicides in terms of potency, and has in the present study, the snails showed several the advantage of yielding other products of behavioural responses, including the `distress pharmaceutical and industrial importance. The use of syndrome' described for other planorbid species by plant molluscicides may not only eliminate the Harry and Aldrich (1963) (55); Sullivan and Cheng economic burden of importing expensive synthetic (1975) (56); Van Aardt and Coertze (1981) (57), molluscicides, but could also stimulate growth of Brackenbury and Appleton (1999) (31), indicative of small-scale industries in developing countries. More intoxication. Swelling of the tissues was not restricted emphasis must, however, be placed on agronomic to the tentacles, but involved the whole cephalopedal and organizational aspects, including community mass. According to Brackenbury and Appleton (1999) participation, if plant molluscicides are to be applied (21), the inference from this observation is that the successfully in long-term and self-sustained snail tissues of the cephalopedal mass had accumulated control programmes (7). water, which caused haemorrhage at lethal Some of the major constraints limiting the use of plant concentrations of the active plant extracts. molluscicides at present are lack of adequate Nevertheless, the observations made in this study information on their cost-effectiveness and chronic suggest that the toxic principles in the active plant toxicity, and difficulties of developing viable snail extracts distrupted the permeability of the foot-sole control programmes in rural areas using local surface epithelium by preventing its normal resources (7). In some communities, snail control has osmoregulatory function (21). The toxic effects of the been traditionally carried out using imported synthetic sublethal doses of the plant extracts were, however, chemicals, with little or no involvement of the local reversible after exposure if the snails were moved to people, by health officials and technicians of central toxic extract-free water for a recovery period. This governments and international organizations. observation is in agreement with the findings of Harry However, the use of local labour for cultivating, and Aldrich (1963) ((55) and Van Aardt and Coertze harvesting, processing and applying plant (1981) (57) for Bulinus tropicus and Biomphalaria molluscicides, reduced transportation costs and new glabrata after exposure to copper. Exposure of the methods of screening and extracting the active snails to the active plant extracts examined caused compounds from the plants, can make local plant irreversible cellular damage to Bulinus africanus and molluscicides more cost-effective. The extensive Biomphalaria pfeifferi. According to Brackenbury and knowledge of local plants with toxic and medicinal Appleton (1999) (21), the assumption that the properties which most of the rural people have molluscicidal actions of the active plant extracts was acquired, together with new information on chemo- due to the disruption of the osmoregulatory , will permit focused screening of those physiology of the foot-sole epithelium could be plant families and genera that are most likely to supported by evidence of specific cellular injuries. contain species suitable for effective snail control. Although several investigators have successfully Apart from distruption of the snail's foot-sole tested plant materials for molluscicidal activities using epithelium osmoregulatory physiology, there is also techniques commonly employed in phytochemical the possibility that enzyme-mediated pathways of the and pharmacological studies, more effective snail are affected by the molluscicidal extracts (21) exchange of information is required to develop However, osmolality and electrolyte studies, as well specific research methodologies and snail control as enzymatic, histochemical and biochemical studies strategies (7). In future, more attention must be paid are required to substantiate these possible modes of to the development of simple, cheap and efficient molluscicidal action of the plant molluscicides. extraction and application techniques amenable for In many schistosomiasis-endemic countries of the use in rural communities. With community world, pharmaco-chemical research on molluscicidal development and appropriate technology becoming plants is now gaining the support of government and important elements in most new national socio- non-government institutions at a time when there is a economic plannings, many endemic countries of the slow growth in synthetic molluscicides. During the last world should now support the development and evaluation of plant molluscicides as a new tool in the 70 years, more than 1500 plant species have been implementation of locally and internally directed screened, most of them superficially, for molluscicidal health improvement campaigns. activities. The richness of the flora in most areas of the world where snail-transmitted diseases are endemic, probably suggests that many plants with BLACPMA Vol. 3 Nº 1 – Enero 2004 20

ACKNOWLEDGEMENTS Protectorate, and their relation to human schistosomiasis. Trans. Roy. Soc. Edinburgh In executing this study, I received assistance from 59: 687 ± 691. individuals and institutions. It is my pleasure to 14. Pinto C, Almeida AF (1944). Um novo acknowledge the able assistance of the following metouo de profilaxia da esquistosome people: Dr. Esther K. Mutenda ± for her help in the mansoni. Mem. Inst. Osw. Cruz. 40: 291 ± extraction of the plant materials; Mrs. Patience P. 296. Koloko ± for her assistance in the collection and 15. Lemma AP, Duncan GJ, Mazengia B (1978). collation of the plant materials used in this study; Mr. Control of schistosomiasis with the use of Samuel O. Adewale ± for his technical assistance; endod in Adwa, Ethiopia: results of a five- and Prof. Clement O. Adewunmi ± for his valuable year study. Proceedings of the International comments and general interest in this study. This Congress on Schistosomiasis, Cairo, S. O. P. study was partially supported by the University of Press, pp. 415 ± 436. Durban-Westville's Research Grant Number R642, 16. Amorin JP, Pessoa SB (1962). Experiencia for which I am grateful to the Council of the de algunos vegetais como molluscocida. University. Revista Brasileira de Malariologia e Doencas Tropicais 14: 254 ± 258. REFERENCES 17. Silva MJM, Sousa MP, Rouquayrol MZ (1971). Actividade molluscicida de plantas do 1. Jordan P (2000). From Katayama to Dakhla nordeste Brasileiro. Revista Brasileira de Oasis: The beginning of epidemiology and Farmacia 52: 117 ± 121. control of bilharzias. Acta Tropica 77: 9 ± 40. 18. Barbosa FS, Mello DA (1969). Acao 2. Bilharz T (1852). Ein beitrag zur molluscicida de plantas. Revista Brasileira de helminthographis humana. Zeitschrift fur Pesquisas Medica e Biologia 2: 364 ± 370. Wissenschaftliche Zoologie 4: 53 ± 76. 19. Brackenbury TD, Appleton CC (1997). Acute 3. Bilharz T (1853). Fernere Mitteilungen yber toxicity evaluation of the plant molluscicide Distomum haematobium. Zeitschrift fur Apodytes dimidiata (Icacinaceae), to Eisenia Wissenschaftliche Zoologie 4: 454 ± 455. fetida (Oligochaetae) and Oreochromis 4. Leiper RT (1911). Note on the presence of a mossambicus (Cichilidae) in South Africa. lateral spine on the eggs of Schistosoma Acta Tropica 63: 1 ± 14. japonicum. Trans. Roy. Soc. Trop. Med. Hyg. 20. Brackenbury TD, Appleton, CC (1997). A 4: 133 ± 136. comprehensive evaluation of Agava 5. Leiper RT (1911). Some variations in the attenuata, a candidate plant molluscicide in character and position of the spine in eggs of South Africa. Acta Tropica 68: 201 ± 213. Schistosoma haematobium. J. Trop. Med. 21. Brackenbury TD, Appleton CC (1999), Hyg. 14: 120 ±121. Structural damage to the foot-sole epithelium 6. Leiper RT; Atkinson EL (1915). Observations of Bulinus africanus following exposure to a on the spread of Asiatic Schistosomiasis. plant molluscicide. Malacologia 41: 393 ± Br. Med. J. I: 201 ± 203. 401. 7. Kloos H, McCullough FS (1982). Plant 22. Medina FR, Woodbury R (1979). Terrestrial Molluscicides. Planta Medica, 46: 195 - 209. plants molluscicidal to Lynmaeid hosts of 8. Webbe G (1987). The use of molluscicides in Fasciola hepatica in Puerto Rico. J. Agric. the control of human trematode infections. In: Univ. Puerto Rico 63: 366 ± 370. ªThe Toxicology of Molluscicidesº. G. Webbe 23. Alzerreca A, Arboleta B, Hart G (1981). Ed., Pergamon Press, Oxford, pp. 1 ± 11. Molluscicidal activity of natural products. The 9. WHO (1985). The control of Schistosomiasis. effect of Solanum glycosidic alkaloids on WHO Technical Report Series, Në. 728. Lymnaea cubensis snails. J. Agric. Univ. 10. WHO (1993). The control of Schisosomiasis. Puerto Rico 57: 69 ± 75. WHO Technical Report Series, Në. 830. 24. Lemma A, Yau P (1974). Studies on the 11. Archibald RG (1933). The use of the fruit of molluscicidal properties of Endod (Phytolacca the tree Balanites aegyptiaca in the control of dodecandra). II. Comparative toxicity of Schistosomiasis in the Sudan. Trans. Roy. various molluscicides to fish and snails. Soc. Trop. Med. Hyg. 27: 207 ± 210. Ethiop. Med. J. 12: 109 ± 113. 12. Wager VA (1936). The possibility of 25. Maegraith B (1958). Schistosomiasis in eradicating bilharzias by extensive planting of China. Lancet I (7013): 208. the tree Balanites. South Afric. Med. J. 10: 10 26. Adewunmi CO, Sofowora EA (1980). ± 11. Preliminary screening of some plant extracts 13. Mozley A (1939). Fresh-water of the for molluscicidal activity. Planta Medica 39: Tangayika Territory and the Zanzibar 57 ± 65. BLACPMA Vol. 3 Nº 1 – Enero 2004 21

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54. Hostettmann K, Kizu H, Tomimori T (1982). RECOMENDAMOS Molluscicidal properties of various saponins. Planta Medica 44: 34 ± 35. BLACPMA 55. Harry HW, Aldrich DV (1963). The distress www.blacpma.cl syndrome in Taphius glabratus (Say) as a reaction to toxic concentrations of inorganic ions. Malacologia 1: 283 ± 287. 56. Sullivan J, Cheng T (1975). Heavy metal toxicity to Biomphalaria glabrata (Mollusca: ASOCIACIÓN DE FITOMEDICINA DE ARGENTINA Pulmonata). Annals New York Acad. Sci. www.plantasmedicinales.org 266: 437 ± 444. 57. Van Aardt WJ, Coertze DJ (1981). Influence of copper sulphate on the water and RED BOSQUE electrolyte balance of the fresh water snail www.prodar.org/redbosque Bulinus tropicus. South Afric. J. Zool. 16: 193 ± 199.

INTERNACIONAL SOCIETY OF OTHER IMPORTANT REFERENCES ETHNOPHARMACOLOGY

http://www.ethnopharmacology.org A. WHO (1961). Molluscicides. Second

Report of the Expert Committee on Bilharziasis. WHO Technical Report Series, No. 214. REVISTA DE FITOTERAPIA DE ESPAñA B. WHO (1965). Molluscicide screening http://www.fitoterapia.net and evaluation. Bull. Wld Hlth Org. 33: 567 - 581. C. WHO (1980). Epidemiology and BOLETÍN PROCASUR Control of Schistosomiasis. WHO http://www.procasur.org Technical Report Series, No. 643.

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