Control of schistosomiasis in the Gezira

For the control of schistosomiasis in irrigated agricultural schemes, the inhabitants must have: 1) Enough potable water. 2) Latrines. 3) Proprer health education to motivate the community to participate in the control. 4) Proper diagnostic facilities. 5) Proper availabel chemotherapy. 6) Focal mullusciciding. 7) If possible trial of biological and environmental methods control. Following the above methods, we could reduce the prevalence of schistosomiasis from over 50% to about 13%. The important achievement, is the improvement of the health of the community; therefore more production and reduced morbidity and mortality.

Antitumor activity of chemical modified natural compounds

Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1). Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

Prevalence and control of Babesiosis in the Americas

This review presents up-to-date information on the distribution and control measures of babesiosis in Latin America. Bovine babesiosis caused by Babesia bovis and B. bigemia will be emphasized. The disease is endemic is most countries and poses a serious economic burdenon livestock production in the region (U.S.$1365 million/year, FAO, 1989). Of the estimated 250 million cattle in Central and South America, approximately 175 million (70%) are in tick-infested regions. Humid, tropical and subtropical areas favor development of the main vector, the one-host tick Boophilus microplus. In many regions bovine babesiosis is enzootically stable as consequence of a balanced host-parasite relationship. However, Latin America offers a wide range of epidemiologica conditions that are influenced by variations from tropical to cool climates and by susceptible purebred cattle that are regularly imported to upgrade local stocks. The control measures employed in most countries for babesiosis esentially rely on chemotherapy, use of acaricides for B. microplus, and to a lesser degree, on immunization methods. In general, these measures are expensive, time consuming, and in many cases, provide limited success. Finally, the zoonotic potential ob babesiosis will be addressd, with special emphasis on the situation in the United States. Even though bovine babesiosis has long been eradicated from the U.S.A., human babesiosis in endemic in the northeastern region of the country.

Epidemiology and control of malaria and other arthropod born diseases

Malaria and other arthropod born diseases remain a serious public health problem affecting the lives and health of certain social groups when the two basic strategies to control fail due to : (1) the lack of effective chemoprophylaxis/chemotherapy or the rapid development of drug resistance of the infectious agents and (2) the ineffectiveness of pesticides or the arthropod vectors develop resistance to them. These situations enhances the need for the design and implementation of other alternatives for sustainable health programmes. The application of the epidemiological methods is essential not only for analyzing the relevant data for the understanding of the biological characteristics of the infectious agents, their reservoirs and vectors and the methods for their control, but also for the assessment of the human behaviour, the environmental, social and economic factors involved in disease transmission and the capacity of the health systems to implement interventions for both changes in human behaviour and environmental management to purpose guaranteed prevention and control of malaria and other arthropod born diseases with efficiency, efficacy and equity. This paper discuss the evolution of the malaria arthropod diseases programmes in the American Region and the perspectives for their integration into health promotion programs and emphasis is made in the need to establish solid basis in the decision-making process for the selection of intervention strategies to remove the risk factors determining the probability to get sick or die from ABDs. The implications of the general planning and the polices to be adopted in an area should be analyzed in the light of programme feasibility at the local level, in the multisectoral context specific social groups and taking in consideration the principles of stratification and equity

Basic biochemical investigations as rationale for the design of original antimalarial drugs. An example of phospholipid metabolism

The future of antimalarial chemotherapy is particulary alarming in view of the spread of parasite cross-resistances to drugs that are not even structurally related. Only the availability of new pharmacological models will make it possible to select molecules with novel mechanisms of action, thus delaving resistance and allowing the development of new chemotherapeutic strategies. We reached this objective in mice. Our approach is hunged on fundamental and applied research begun in 1980 to investigate to phospholipid (PL) metabolism of intraerythrocytic Plasmodium. This metabolism is abundant, specific and indispensable for the production of Plasmodium membranes. Any drug to interfere with this metabolism blocks parasitic development. The most effective interference yet found involves blockage of the choline transporter, which supplies Plasmodium with choline for the synthesis of phosphatidylcholine, its major PL, this is a limiting step in the pathway. The drug sensitivity thereshold is much lower for the parasite, which is more dependent on this metabolism than host cells. The compounds show in vitro activity against P. falciparum at 1 to 10 nM. They show a very low toxicity against a lymphblastoid cell line, demonstrating a total abscence of correlation between growth inhibition of parasites and lymphoblastoid cells. They show antimalarial activity in vivo, in the P. berghei or P. chabaudi/mouse system, at doses 20-to 100-fold lower than their in acute toxicity limit. The bioavailability of a radiolabeled form of the product seemed to be advantageous (slow blood clearance and no significant concentration in tissues). Lastly, the compounds are inexpensive to produce. They are stable and water-soluble.

The treatment of falciparum malaria in children with halofantrine suspension

Malaria treatment of children is particulary difficult because of the absence of palatable suspensions for young children. Halofantrine hydrochloride is available as a suspension which is both palatable and simple to administer, and has been studied in a number of trials in the past 5 years. Children (331) ranging from 4 months to 17 years of age (mean 4.7 years) were treated with the 5% suspension using various dose regimens and 364 children ranging from 4 months to 14 years of age (mean 5.7 years) were treated with the 2% suspension 6 hourly for 3 doses. Using the 3-dose regimen there were only 2/462 (0.4%) who failed to clear the initial parasitaemia. Recrudescence occurred in 28/367 (7.6%) children with evaluable follow up data. The mean parasite clearance time in this group was 57.1h (n = 417) and the mean fever clearance time was 50.9 h (n = 325). Symptoms related to malaria cleared rapidly following treatment generally by 24-48 h post treatment. Side effects possibly related to treatment were uncommon but were similar to those reported in adults. The frequency of diarrhoea and abdominal pain was lower than that seen in adults and was also less frequent following multiple doses and the use of the more dilute suspension. Since was evidence that the majority of recrudescences were seen in younger children or those living in areas with low or seasonal transmission it is recommended that a further course of treatment 7 days later is given to these patients to prevent recrudescence. Halofantrine suspension appears to be effective and well tolerated in children and is a useful addition to the drugs available for the treatment of paediatric malaria.

Harmonization of research and control in schistosomiasis

I have been employed by several different organizations during over 30 years working on schistosomiasis, the majority spent in endemic areas of Caribean, South America, Africa and the Western Pacific. Much of the work is best classified as applied research but sometimes it strayed to the extremes of either public health control programmes or pure research. Over this period, there have been several significant research developments that have altered our whole approach to control. Ideally, research and control should complement each other but, in reality, they sometimes have conflicting objectives. Public health workers understandably wish to provide immediate, shot-term protection to the communities in their care, but research workers may, within ethical limits, reasonably want to observe untreated communities for extended periods in order to understand the underluing process of transmission, disease pathogenesis and immunity to help develop more effective control measures. An example of this situation has occured recently in Senegal where water development projects seem to have favoured the introduction and spreed of Schistosoma mansoni in the Senegal River Basin. I have been asked to be the scientific consultant to the newly formed ESPOIR programme, linking European research organizations and the Senegal Ministry of Health, to reconcile the conflictiong aims of public health workers, wishing to use whatever funds can be obtained for an immediate chemotherapy to try to eliminate the focus, at present confined to the vicinity of a relatively small, commercially run sugar irrigation scheme; and research workers who see a rare chance to study the development of immune mechanisms in a adults in a community not previously exposed to the infection. This information could prove invaluable in understanding the development of immunity and the pathogenesis of disease, leading eventually to the development of vaccines to revolutionise the future approach to schistosomiasis...

Morphological features of collagen degradation in advanced hepatic schistosomiasis of man

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections taken from patients with periportal ("pipe-stem") fibrosis caused by schistosomiasis mansoni. Besides present of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlargend portal spaces also showed hyperplasia of elastic tisue and disarray of smooth muscle fibers following the destrution of portal vein branches. Ultrastructural cahnges represented by focal lytic and/or electron dense alterations of colagen fibrils were similar to those first seen in experimental material and designated as "chronic collagen degradation". Elastin and related microfibrils were also affected by focal condensation, fragmentation, distorsion and dissolution. Schistosome eggs were scanty in the tissue sections examined. Matrix degradation represented involuting changes related to the progressive diminution of parasite aggression, which occurs spontaneously with age or after cure by chemotherapy. Changes of focal matrix degradation now being described represent the basic morphological counterpart of periportal fibrosis involution documented clinically, especially by ultrasonography, in patients with hepatosplenic schistosomiasis submitted to curative chemotherapy.

Experiences with the control of schistosomiasis mansoni in two foci in Central Africa

Experiences with population-based chemotherapy and other methods for the control of schistosomiasis mansoni in two subsaharan foci are described. In the forest area of Maniema (Zaire), intense transmission of Schistosoma mansoni, high prevalences and intensities of infection, and important morbidity have been documental. Taking into account the limited financial means and the poor logistic conditions, the control strategy has been based mainly on targeted chemotherapy of heavily infected people (>600 epg). After ten years of intervention, prevalences and intensities have hardly been affected, but the initial severe hepatosplenic morbidity has almost disappeared. In Burundi, a national research and control programme has been initiated in 1982. Prevalences, intensities and morbidity were moderate, transmission was focal and erratic in time and space. A more structural control strategy was developed, based on screening and selective therapy, health education, sanitation and domestic water supply. Prevalences and intensities have been considerably reduced, though the results show focal and unpredicatable variations. Transmission and reinfection were not signifcantly affected by chemotherapy alone, and eventual outcome of repeated selective treatment appears to be limited by the sensitivity of the screening method. Intestinal morbidity was strongly reduced by community-based selective treatment, but hepatosplenic enlargement was hardly affected; this is possibly due to the confounding impact of increasing malaria morbidity. The experiences show the importance of local structures and conditions for the development of an adapted control strategy. It is further concluded that population-based chemotherapy is a highly valid tool for the rapid control of morbidity, but should in most operational conditions not be considered as a tool for transmission control. Integration of planning, execution and surveillance in regular health services...

O tratamento específico como arma no controle da esquistossomose

The specific treatment of schistosomiasis has been though to prevent or revert severe forms of the disease, since 1957. Starting in 1977, prospective and controlled studies performed in different endemic areas of Brazil were able to confirm such facts. The new drugs, of high efficacy and well tolerated - Oxamniquine and Praziquantel - can actually prevent and cure the severe forms of some patients, contributing to change the morbidity pattern of the disease, thus being considered as important weapons in its control. Analysis of the Brazilian articles on the subject is presented.

Some personal views on the control of schistosomiasis mansoni

Our views are based, on a recent study of a district of Uniao dos Palmares (Alagoas). Although being a very compact community (32 city blocks holding two thousand families), transmission is very uneven, the geometric mean egg counts in the various blocks ranging between extremes of 96 and 1920. (Results do not correlate with the availability of domestic water supply). We thus are led to conclude that: (a) transmission is primarily peridomestic, resulting from pollution of open ditches and other collections of water; (b) control of transmission can be done on a selective basis, requiring quite medest investments. Given the inefficacy of population-based chemotherapy, when used alone, the author insists that this alternative cannot any longer be overlooked. He also regrets the emphasis placed upon vaccine development; allegations that this would, at any rate, prevent severe morbidity can be dismissed, since-whatever the cause-morbidity due to schistosomiasis has been rapidly declining in Northeast Brazil.

New approaches for the control and eradication of schistosomiasis in Venezuela

Schistosomiasis in Americawith the exception of Brazil, behaves as a chronic mild disease with few clinical manifestations due to low parasite burden. These features restrict the clinical and parasitological diagnosis. The most commonly used stool examination method, Kato-Katz, becomes intensitive when the majority of individuals excrete less than 100 eggs/g of feces. In view that antigen-detecting techniques have not been able to reveal light infections, the antibody detecting assays remain as a very valuable diagnostic tool for epidemiological surveillance. The Venezuelan Schistosomiasis Research group (CECOICE) has designed a mass chemotherapy strategy based on sero-diagnosis. Since blood sampling is one of the important limitating factors for large seroepidemiological trials we developed a simple capillary technique that sucessfully overcomed most of the limitations of blood drawing. In this sense, ELISA seems to be the most adecuate test for epidemiological studies. Soluble egg Schistosoma mansoni antigen (SEA) has been largely used in Venezuela. The sensitivity ELISA-SEA in our hands is 90% moreover its specific reach 92% when populations from non-endemic areas but heavily infected with other intestinal parasites are analyzed. The Schistosomiasis Control Program is currently carrying out the surveillance of endemic areas using ELISA-SEA as the first screening method, followed by the Circumoval Precipitin test for validation assay. The results with these two serological techniques allowed us to defined the criteria of chemotherapy in populations of the endemic areas. On the search of better diagnostic technique, Alkaline Phosphatase Immunoenzyme Assay (APIA) is being evaluated in field surveys.

Controle da esquistossomose mansônica em área de baixa transmissao

The schistosomiasis is transmitted by Biomphalaria tenagophila in our study area (Pedro de Toledo, Sao Paulo, Brazil). From 1980 to 1990 epidemiological surveys in a population of 4.000 inhabitants, has shown that: prevalence Kato-Katz (KKT), immunofluorescence (FT) and intradermal (IDT) techniques were 22.8%, 55.5% and 51.8% respectively; intensity of infection was low, 58.5 eggs per gram of faeces (epg); there were no symptomatic cases; prevalences were higher in mates, children and rural zone; index of potential contamination was 57.5% in the age group 5 to 20 years; 2/3 of patients were autochtonous; cases were no-randomly aggregated; transmission was focal and only 0.4% of snails were infected; water contacts through recreation showed the most important odds ratio; knowledge, attitudes and practices were satisfatory. From the epidemiological control findings a control programme was carried out; yearly faeces exams, chemotherapy, molluscocide, health education and sanitation. Thus, the prevalence decreased sharply to 3.3% and intensity of infection to 30.3 epg; the incidence rates ranged between 0.4% and 2.5% annualy; the sanitation became better and the youngsters were the main target in prophylaxis. To improve control, immunodiagnosis has to be conducted and the involvment of the population should be increase. However, we cannot forget that re-infection and the involvment of the population should be increase. However, we cannot forget that re-infection, therapeutic failure, etc, could play a major role in the maintnance this residual prevalence.

Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis mansoni

Schistosomiasis control seems to be different in countries were low parasitic burden and asymptomatic clinical patients are the features of majority of cases. Immunological methods must substitute the traditional coprologic techniques used for some decades in the Control Program. Circumoval Precipitin Test (COPT), intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using as tools for seroepidemiologic studies. COPT and ELISA were performed after treatment to known their utility when impact of chemotherapy must be assessed. One hundred sixty five persons were followed up 3, 6, 9 and 12 months after treatment. The mean sensitivity of CPT studied by age groups was 95.6% which is very important considering that 88.4% of the studied population excreted less than 100 egg/gr of feces, while sensitivity of intradermal test was 58.2%. Children showed the highest ractivity to COPT. When treatment is effective, COPT reactivity progressively disminish until become negative one year later. In the non cure group, the COPT reactivity disminished but never below 20%. ELISA-SEA did not modify one year after treatment. Effort should be made to isolate fractions of eggs Schistosoma mansoni whose antibodies disappear after treatment.

Esquistossomose mansoni: tratamento medicamentoso

It is the specific treatment of mansoni schistosomiasis that aims to act directed on the parasite, through chemotherapy. Constitutes fundamental indication to the treatment of schistosomiasis active forms, that is, these determined by the presence of living eggs in the feces or in material from rectal biopsy, since eventual contra indications are respected. Two are the medicaments actually used: oxamniquine, used in the single dosage of 15mg/kg, V.O. for adults and 20mg/kg V.O. for children divided in two doses, offers a percentage of 30 to 40% of cures, evaluated by quantitative "oogram" and prazinquantel, in the single dose of 60 mg/kg V.O., presents a cure index of 30% however in seriate doses, of 60mg/kg during 3 days or 30mg/kg, 6 days, cure percentage is elevated to 95% evaluated by oogram. The evaluation of the treatment by quantitative or qualitative examination methods does not show the same sensibility. The percentage of cure according to feces examination, the quantitative of Kato-Katz or the qualitative (sedimentation), showed indexes from 90 to 100% for either one of the drugs, even in single dose, which evidences the difference of methodology of therapeutic evaluation. Tolorance to both medicaments is from good to regular, with collateral effects in 30 to 40% of the patients.