Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of repeated chemotherapy on morbidity due to schistosomiasis mansoni was evaluated in Gihungwe (initial prevalence 58%) and Buhandagaza/Kizina (33%), two village clusters in Burundi. Surveys were carried out with reference to the first treatment (month 0) at months -6, -3, 0, 3, 6, 9, 12, 24, and 36. Praziquantel (40 mg/kg) was given at months 0, 12, 24, and 36 to those showing eggs in the feces with a single 28-mg Kato slide. At each survey, duplicate Kato smears were examined, and all participants responded to a standardized medical history interview and underwent a clinical examination. In the three preintervention surveys, spleen and liver rates remained stable at the community and the individual level. The frequencies of diarrhea and abdominal pain varied to some extent, but they were consistently higher in the most heavily infected villages and age groups and remained relatively stable at the individual level. At the final survey, the prevalence of infection had decreased to 25%, and the frequency of diarrhea from 19-26% to 10% in both village clusters. This impact was strongest in the younger age groups. The frequency of abdominal pain was reduced only at the short term and in selected age groups. Organomegaly decreased only to a limited extent in those treated, and increased in those not treated, possibly due to the impact of malaria. The net result was that no measurable impact of the treatments on organomegaly at the community level could be demonstrated. In the light of these results, the relevance of community-based chemotherapy in moderate foci is questioned.
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PMID:Impact of repeated community-based selective chemotherapy on morbidity due to schistosomiasis mansoni. 798 56

Drug development offers potential solutions to a number of tropical health diseases, although the expense of pharmaceutical research and lack of return on investment has limited the production of new agents. The greatest successes have been through the development of single dose therapy and mass treatment control programmes for a number of diseases. We review some of the current treatment regimens for malaria, intestinal helminth infection, onchocerciasis, filariasis and schistosomiasis, and their use in clinical practice. Geographical spread and emergence of drug resistant parasites have hindered the control of malaria, the most important global parasitic infection. Artemisinin compounds have proved effective antimalarial agents producing rapid reduction of parasite load and can be used in combination treatment regimens to combat multidrug resistance. Intestinal helminth infections are widespread, giving rise to nutritional deficiencies and impaired childhood cognitive development. Pregnant women in developing countries are at increased risk of morbidity. Treatment with a single dose benzimidazole such as albendazole or mebendazole has beneficial effects on morbidity and rates of transmission. Diethylcarbamazine has been used in the treatment of onchocerciasis and human filariasis. A complicated escalating dose regimen over several weeks is associated with systemic and allergic reactions and may require corticosteroid cover. Simplified regimens for mass population treatment with ivermectin have proved useful and been used in combination with single dose albendazole and diethylcarbamazine. The African Programme for Onchocerciasis Control in West and Central Africa has been one of the most successful mass control programmes virtually eliminating new infections by a combination of chemotherapy, education and vector control. Schistosomiasis is of increasing importance as a result of the creation of new snail habitats by agricultural and economic development. Praziquantel has become the most widely available and effective chemotherapy for schistosomiasis. There have been a number of reports of persistent schistosome egg shedding after treatment posing concerns about the emergence of drug resistance. Eflornithine has been successfully used in patients with human trypanosomiasis failing melarsoprol therapy however expense and availability have limited its potential. Mass control treatment programmes have targeted schoolchildren, adolescents and pregnant women. The integration of schistosomiasis, onchocerciasis, filariasis and helminth control programmes has been considered as a cost-effective method of delivering treatment. It is likely that future control will be based on this optimisation and integration of existing regimens, rather than the development of new agents.
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PMID:Drug treatment of tropical parasitic infections: recent achievements and developments. 1112 30

Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importance. At present, there is no vaccine available, and chemotherapy is the cornerstone of schistosomiasis control. Praziquantel is the drug of choice. Oxamniquine has become difficult to obtain and metrifonate has recently been withdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for prevention and cure of schistosomiasis. Significant progress has been made with artemether, the methyl ether of dihydroartemisinin, already widely used for the treatment of malaria. The present article reviews the literature that led to the development of artemether for chemoprophylaxis in schistosomiasis, and it summarises the experiences so far obtained with its use to control schistosomiasis in different endemic settings. Topics covered include an overview of the global burden of schistosomiasis and approaches for its control; the nature and features of artemisinin and related derivatives, initially discovered as antimalarials, other bioactivities, and their recent discovery of antischistosomal properties; a historic account disclosing the antischistosomal activity of artemether; in vivo assessment of drug susceptibility of different developmental stages of schistosome parasites; artemether-induced pathology evidenced by scanning and transmission electron microscopy; the possible mechanism of action; in vivo studies with combination therapy of artemether and praziquantel; results of randomised controlled clinical trials of oral artemether for the prevention of patent infection and morbidity; and, ultimately the translation of this knowledge into public health action in different endemic settings towards a more integrated approach of schistosomiasis control.
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PMID:Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites. 1177 54

Praziquantel is the current mainstay for morbidity control of schistosomiasis. Artemisinin and its derivatives, widely used for the treatment of malaria, also display antischistosomal properties. The present study is an effort to assess the therapeutic efficacy of artesunate, an artemisinin derivative, in Schistosoma haematobium infections in a human population. The efficacy of artesunate and praziquantel were comparatively studied in primary schoolchildren from two villages, Lampsar (n=180) and Makhana (n=108), located along the Lampsar river in the delta of the Senegal River Basin in Northern Senegal (West Africa). In each village, half of the infected children were treated with a single oral dose of 40 mg/kg praziquantel and half with artesunate following the recommended malaria monotherapy regimen. For both drugs, cure and egg count reduction rates were, without apparent explanation, higher in Makhana than in Lampsar. In both villages, high and nearly comparable egg count reduction rates were obtained with both drugs at each follow-up after treatment (5, 12 and 24 weeks) in the heavy infected group of children (>50 eggs/10 ml of urine). No major adverse effects were observed. The results demonstrate that artesunate is effective against S. haematobium, but the results obtained with praziquantel were consistently better.
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PMID:Efficacy of artesunate and praziquantel in Schistosoma haematobium infected schoolchildren. 1190 4

Schistosomiasis ranks second, behind malaria, among human parasitic diseases in terms of public health and socioeconomic importance in tropical and sub-tropical areas. Worldwide, 1 of 30 people has schistosomiasis. Up to 300 million people are infected, and 600 million live in environments where infection is a risk. Tourists from non-endemic areas are contracting schistosomiasis due to the rise in "off-the-beaten-track" tourism. Praziquantel is effective against all species of schistosomes and early treatment is curative. Schistosomiasis is an insidious disease, however, so worldwide the disease is not diagnosed early. The most frequent and dangerous complication of the disease is variceal hemorrhage due to hepatic fibrosis. Variceal hemorrhage is the first symptom in 58% of cases. A variety of treatments for variceal hemorrhage are available. Exsanguination from variceal hemorrhage is possible; therefore, aggressive stabilization of the patient by the use of multiple therapies is appropriate. Most patients treated after esophageal hemorrhages do not experience reversal of hepatic fibrosis. For this reason, healthcare providers need an increased awareness of schistosomiasis to enable earlier detection and treatment in world travelers.
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PMID:Schistosomiasis: implications for world travelers and healthcare providers. 1597 62

Praziquantel (PZQ) is the drug of choice for the treatment of human schistosomiasis. It is estimated that about 200 million people in the world are currently affected by this tropical disease. Now PZQ is also used in malaria treatment. The usefulness of PZQ as antimalarial drug is important because of rapid development of resistance to usually applied drugs. PZQ undergoes extensive metabolism in human body, mainly in liver by two cytochrome P-450 isoenzymes 2B1 and 3A. As the result of these biotransformations numerous mono- and dihydroxylated derivatives in B, C and D ring are formed. Two metabolites have been fully identified and described, as cis- and trans-4-hydroxypraziquantel. Up to now there were created many different in vitro and in vivo models of PZQ biotransformations. In vitro model of PZQ biotransformation was created by using human cytochrome P-450 3A4 expressed in Eschelichia coli and Saccharomyces cerevisiae. In the first experiment we have used human cytochrome P-450 3A4 from Escherichia coli (isolated on NTA-column). In the second experiment microsomes isolated from Saccharomyces cerevisiae containing coexpressed human CYP 3A4, human CYP-reductase and human cytochrome b5 were used. The reactions were monitored by HPLC and MS.
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PMID:Biotransformation of praziquantel by human cytochrome p450 3A4 (CYP 3A4). 1735 89

Plasmodium yoelii and Schistosoma mansoni co-infections were studied in female BALB/c mice aged 4-6 weeks to determine the effect of time and stage of concomitant infections on malaria disease outcome. Patent S. mansoni infection in BALB/c mice increased malaria peak parasitemia and caused death from an otherwise non-lethal, self-resolving P. yoelii malaria infection. Exacerbation of malaria parasitemia occurred during both pre-patent and patent S. mansoni infection resulting in a delay of 4-8 days in malaria parasite resolution in co-infected mice. Praziquantel administered to mice with patent schistosome infection protected from fatal outcome during co-infection. However, this treatment did not completely clear the worm infestation, nor did it reduce the peak malaria parasitemia reached, which was nonetheless resolved completely. Hepatosplenomegaly was more marked in schistosome and malaria co-infected mice compared to either infection separately. The results suggest a complex relationship between schistosome co-infection and malaria disease outcome in which the timing of malaria infection in relation to schistosome acquisition is critical to disease outcome and pathology.
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PMID:Plasmodium yoelii: adverse outcome of non-lethal P. yoelii malaria during co-infection with Schistosoma mansoni in BALB/c mouse model. 1936 21

Schistosome parasites are the causative pathogens of schistosomiasis (bilharzia), a disease of worldwide significance. In terms of patient numbers, schistosomiasis ranks second to malaria as a parasitosis affecting more than 200 million people of the tropics and subtropics. Since the 1970s Praziquantel (PZQ) is the drug of choice and nearly exclusively used for treatment. However, drug resistance is an increasing threat, particularly with respect to large-scale PZQ administration programs. Last decade's research indicated that resistance against PZQ can be induced under laboratory conditions, and field studies provided first indications for the possibility of reduced PZQ efficacy. Furthermore, clear evidence for the molecular armamentarium of schistosomes with multidrug transporters was found, one of which was responding to PZQ challenge. Also the development of a vaccine still represents an elusive goal, although effort and time have been invested in this subject. In light of these facts it is commonly accepted that new drugs are urgently needed. Research on signal transduction processes in Schistosoma mansoni has provided an unexpected and novel perspective towards this end. Molecular, biochemical, and physiological studies elucidating principles of schistosome development have demonstrated the essential role of protein kinases (PKs). In humans, PKs are known to be involved in cancer development. Since a variety of approved anticancer drugs targeting PKs exist, first studies have been performed to investigate whether these drugs are able to also inhibit schistosome PKs. Indeed, promising results have been obtained indicating the potential of PKs as privileged targets for new concepts in fighting schistosomes.
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PMID:Protein kinases as potential targets for novel anti-schistosomal strategies. 2260 48

The clinical manifestations of schistosomiasis pass by acute, sub acute and chronic stages that mirror the immune response to infection. The later includes in succession innate, TH1 and TH2 adaptive stages, with an ultimate establishment of concomitant immunity. Some patients may also develop late complications, or suffer the sequelae of co-infection with other parasites, bacteria or viruses. Acute manifestations are species-independent; occur during the early stages of invasion and migration, where infection-naivety and the host's racial and genetic setting play a major role. Sub acute manifestations occur after maturity of the parasite and settlement in target organs. They are related to the formation of granulomata around eggs or dead worms, primarily in the lower urinary tract with Schistosoma haematobium, and the colon and rectum with Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum and Schistosoma mekongi infection. Secondary manifestations during this stage may occur in the kidneys, liver, lungs or other ectopic sites. Chronic morbidity is attributed to the healing of granulomata by fibrosis and calcification at the sites of oval entrapment, deposition of schistosomal antigen-antibody complexes in the renal glomeruli or the development of secondary amyloidosis. Malignancy may complicate the chronic lesions in the urinary bladder or colon. Co-infection with salmonella or hepatitis viruses B or C may confound the clinical picture of schistosomiasis, while the latter may have a negative impact on the course of other co-infections as malaria, leishmaniasis and HIV. Prevention of schistosomiasis is basically geared around education and periodic mass treatment, an effective vaccine being still experimental. Praziquantel is the drug of choice in the treatment of active infection by any species, with a cure rate of 80%. Other antischistosomal drugs include metrifonate for S. haematobium, oxamniquine for S. mansoni and Artemether and, possibly, Mirazid for both. Surgical treatment may be needed for fibrotic lesions.
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PMID:Human schistosomiasis: clinical perspective: review. 2568 50

Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated.
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PMID:Antischistosomal activity of artemisinin derivatives in vivo and in patients. 2690 77


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