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PubMed2006

Anthelmintic resistance and alternative control methods.

Anthelmintic resistance has been a problem almost from the first use of the drugs introduced during the past 50 years. Evaluation of anthelmintics on a specific farm is essential to determine which drugs may be used in controlling parasite numbers. Treatment of livestock during the season in which parasite transmission is unfavorable lessens pasture contamination. Targeting treatment places less pressure on susceptible worms, diluting the resistant parasite population. Pasture management and using safe pastures for animals at highest risk lower pasture exposure. Selection for individual animals resistant to the effects of parasites lessens the need for use of anthelmintics. Alternatives to anthelmintics include cryptic antigen vaccines, copper wires, and biologic compounds.

Animals↗
PubMed2006

Sericea lespedeza hay as a natural deworming agent against gastrointestinal nematode infection in goats.

Infection with gastrointestinal nematodes (GIN), particularly Haemonchus contortus, is the biggest constraint to profitable goat production in the United States (US). Due to widespread prevalence of anthelmintic resistance in goat GIN, alternative, non-chemical control methodologies are needed to increase profitability of small ruminant industries. A study was designed to test the efficacy of a high condensed tannin (CT) legume, sericea lespedeza [SL, Lespedeza cuneata (Dum.-Cours. G. Don)] against GIN of goats fed in confinement. The goats were given a trickle infection of 500 H. contortus larvae/animal three times per week during the trial to simulate natural infection. Twenty Boer bucks (6-8 months old) were fed bermudagrass [BG, Cynodon dactylon (L.) Pers.] hay plus concentrate for 5 weeks in confinement and then 10 animals were switched to SL hay for an additional 7 weeks. Throughout the trial, feces and blood were collected weekly from individual animals to determine fecal egg count (FEC) and blood packed cell volume (PCV). Fecal cultures were made weekly from pooled samples to determine treatment effects on GIN larval development. All goats were slaughtered at the end of the trial, with adult worms in the abomasum and small intestine of each goat recovered, counted, and identified to species. Feeding SL hay to goats significantly (P<0.01) reduced FEC and increased PCV compared with BG hay. In addition, a lower percentage of ova in feces from SL-fed goats developed into infective (L3) larvae. There was a direct effect of SL hay on adult worms, with significantly (P<0.01) lower numbers of both abomasal (H. contortus, Teladorsagia circumcincta) and small intestinal (Trichostrongylus colubriformis) nematodes compared with goats fed BG hay. Feeding SL hay to goats is an effective means of controlling parasitic nematodes and may be a potential supplement/replacement for chemical anthelmintics.

Abomasum↗
PubMed1999

Cost-effectiveness of malaria control in sub-Saharan Africa.

BACKGROUND: Information on the cost-effectiveness of malaria control is needed for the WHO Roll Back Malaria campaign, but is sparse. We used mathematical models to calculate cost-effectiveness ratios for the main prevention and treatment interventions in sub-Saharan Africa. METHODS: We analysed interventions to prevent malaria in childhood (insecticide-treated nets, residual spraying of houses, and chemoprophylaxis) and pregnancy (chloroquine chemoprophylaxis and sulfadoxine-pyrimethamine intermittent treatment), and to improve malaria treatment (improved compliance, improved availability of second-line and third-line drugs, and changes in first-line drug). We developed models that included probabilistic sensitivity analysis to calculate ranges for the cost per disability-adjusted life year (DALY) averted for each intervention in three economic strata. Data were obtained from published and unpublished sources, and consultations with researchers and programme managers. FINDINGS: In a very-low-income country, for insecticide treatment of existing nets, the cost-effectiveness range was US$4-10 per DALY averted; for provision of nets and insecticide treatment $19-85; for residual spraying (two rounds per year) $32-58; for chemoprophylaxis for children $3-12 (assuming an existing delivery system); for intermittent treatment of pregnant women $4-29; and for improvement in case management $1-8. Although some interventions are inexpensive, achieving high coverage with an intervention to prevent childhood malaria would use a high proportion of current health-care expenditure. INTERPRETATION: Cost-effective interventions are available. A package of interventions to decrease the bulk of the malaria burden is not, however, affordable in very-low-income countries. Coverage of the most vulnerable groups in Africa will require substantial assistance from external donors.

Adolescent↗
PubMed1998

Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog.

Resistance to ivermectin and related drugs is an increasing problem for parasite control. The mechanism of ivermectin resistance in nematode parasites is currently unknown. Some P-glycoproteins and multidrug resistance proteins have been found to act as membrane transporters which pump drugs from the cell. A disruption of the mdrla gene, which encodes a P-glycoprotein in mice, results in hypersensitivity to ivermectin. Genes encoding members of the P-glycoprotein family are known to exist in nematodes but the involvement of P-glycoprotein in nematode ivermectin-resistance has not been described. Our data suggest that a P-glycoprotein may play a role in ivermectin resistance in the sheep nematode parasite Haemonchus contortus. A full length P-glycoprotein cDNA from H. contortus has been cloned and sequenced. Analysis of the sequence showed 61-65% homology to other P-glycoprotein/multidrug resistant protein sequences, such as mice, human and Caenorhabditis elegans. Expression of P-glycoprotein mRNA was higher in ivermectin-selected than unselected strains of H. contortus. An alteration in the restriction pattern was also found for the genomic locus of P-glycoprotein derived from ivermectin-selected strains of H. contortus compared with unselected strains. P-glycoprotein gene structure and/or its transcription are altered in ivermectin-selected H. contortus. The multidrug resistance reversing agent, verapamil, increased the efficacy of ivermectin and moxidectin against a moxidectin-selected strain of this nematode in jirds (Meriones unguiculatus). These data indicate that a P-glycoprotein may be involved in resistance to ivermectin and other macrocyclic lactones in H. contortus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Potential for recombinant Babesia bovis antigens to protect against a highly virulent isolate.

Two antigens from Babesia bovis,12D3 and 11C5, were expressed and purified as recombinant proteins in Escherichia coli and used to vaccinate groups of six Babesia-susceptible cattle. These were subsequently challenged with a highly virulent strain of B. bovis. All cattle showed symptoms of disease and most required treatment. Cattle vaccination groups receiving either 12D3 or 11C5 or a combination of both, reduced parasitaemia by approximately fourfold and a number of individual animals appeared to control the parasite infection. Control of parasites correlated with high monocyte numbers late in infection. The results thus confirm the potential usefulness of both antigens but also demonstrate the limitations of current formulations.

Animals↗
PubMed2006

Ocular toxoplasmosis: in the storm of the eye.

Ocular toxoplasmosis (OT) can occur in the children of mothers infected with Toxoplasma gondii during pregnancy. It is not limited to the congenitally infected, but can also occur following adult-acquired infection or as a result of disease reactivation in immune-compromised and pregnant individuals. Many aspects of immune privilege in the eye, including constitutive TGF-beta expression and reduced MHC class 1 expression, would appear at first to favour parasite survival. Conversely, many of the mechanisms that control parasite multiplication in other anatomical sites, such as nitric oxide expression, IFN-gamma and TNF-alpha, are known to disrupt immune privilege and are associated with ocular damage. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction we review the pathogenesis of OT in the murine model.

Animals↗
PubMed1994

Financing mechanisms for village activities in The Gambia and their implications for financing insecticide for bednet impregnation.

The recent enthusiasm for impregnated bednets as a malaria control measure leaves unresolved the question of how to finance them. The National Impregnated Bednet Programme in The Gambia faced the question of how to obtain funds from villages to finance the cost of insecticide, but knew very little about current village fundraising for development purposes. A survey was conducted of such fundraising, and questions also asked about willingness to pay for insecticide and preferred means of paying. All 53 villages surveyed paid taxes/rates, but 34% of villages reported no voluntary fundraising. The most common reason for collecting money was for the maintenance of wells (40% of villages). Collective farming was used as a means of raising money in 32% of villages. There was some variation in the type and extent of fundraising by region and also by the predominant ethnic groups of the village. Villages with voluntary fundraising activities seemed to have well established collective mechanisms for agreeing on sums to be collected and their use, and for collecting and recording income and expenditure. Non-payment was rare, and misuse of funds was not reported. Respondents were asked how much compounds might be willing to pay for insecticide impregnantion: the most frequently cited maximum amounts were D5 and 10, and minimum D1 and 5 (D15 = 1 pound). The paper discusses payment options for insecticide, such as whether the village should be allowed to decide itself how to raise funds, and whether the payment should be made only by households with nets or by a village-wide mechanism such as collective farming.(ABSTRACT TRUNCATED AT 250 WORDS)

Agriculture↗
PubMed1994

Effects and control of highland malaria epidemic in Uasin Gishu District, Kenya.

This report documents the effects of malaria epidemic and how it was controlled in one highland district of Kenya. The effects of the epidemic are presented in terms of mortality, morbidity and school absenteeism; information is from routine and verbal reports. Treatment with chloroquine, amodiaquine and sulphonamide pyrimethamine combinations, limited vector control, and health education were used to control the epidemic. Hospital mortality per month increased by 8.6 times during the epidemic while morbidity went up by 3.7 times. Of the 103 deaths attributed to malaria, 64 (62.1%) occurred in hospital and 39 (37.9%) at home. Most of the home deaths (92.3%), occurred in areas that border the malaria endemic Lake Victoria Basin. The rate of pupil absenteeism ranged from 17.6% to 54.4% in primary schools. The policy implications of the report are discussed.

Absenteeism↗
PubMed1996

Knowledge, practices, and perceptions about malaria in rural communities of Zimbabwe: relevance to malaria control.

A survey of 411 household heads was undertaken in Gokwe district, Zimbabwe, to assess villagers' knowledge, practices and perceptions about malaria and their implications for malaria control. Our results show that although the government has sustained an annual indoor insecticide spraying programme for over four decades, about 50% of respondents did not adequately understand its purpose, with 26% believing that the programme was intended to kill domestic pests, not including mosquitos. During the 1991-92 spraying cycle, 72% of the villagers had their homes sprayed. However, 21% of such villagers refused to have some rooms in their homes sprayed. Householders' understanding of the function of the spraying programme was significantly related to their compliance with it (P < 0.05). A total of 82% of respondents reported not taking any measures to protect themselves from malaria. Taking preventive measures was significantly related to knowledge of the causes of malaria (P < 0.05). The study shows the importance of involving communities in a control programme intended to be to their benefit and of informing them about available options for protection against malaria.

Cooperative Behavior↗
PubMed1997

Mosques against malaria.

In a community-based malaria control project covering a predominantly Muslim population in the United Republic of Tanzania, difficulty was encountered in motivating people to have their mosquito nets reimpregnated with insecticide at six-monthly intervals. Education on this subject was therefore provided in mosques during Friday noon prayers. People who attended these services considered them an appropriate forum for discussing health concerns and viewed them as a credible source of information.

Adult↗
PubMed2006

Inflammatory lesion and parasite load are inversely associated in Leishmania amazonensis infected mice genetically selected according to oral tolerance susceptibility.

Two strains of mice selected according to extreme phenotypes of susceptibility and resistance to oral tolerance (TS and TR mice, respectively) were infected with 1 x 10(7) Leishmania amazonensis promastigotes and studied comparatively. TS mice developed a minor pathology while permitting parasite growth with the presence of increased IL-4, IL-10 and IFN-gamma, and lower NO and IL-2 levels and delayed-type hypersensitivity (DTH). In contrast, in TR mice, footpad swelling was increased but parasite growth was reduced. They produced lower IL-4, IL-10 and IFN-gamma but increased NO, IL-2 levels, DTH, activated spleen macrophages and periarteriolar lymphoid sheaths. The results suggest that the tolerogenic TS mouse profile, with higher IL-10 production, impaired lesion development but also avoided macrophage leishmanicidal activity, maintaining in this manner a silent parasite load. On the other hand, the TR mouse profile contributed to lesion progression with controlled parasite load. To directly address the influence of oral tolerance on infection, mice were gavaged with OVA, and 7 days afterwards were infected and challenged to bystander suppression with OVA in the same footpad. In TR mice gavaged with 25 mg OVA the inflammatory lesion was largely enhanced, while with 5 mg OVA the lesion was diminished. In TS mice the footpad swelling was always lower. However, the bystander effect did not modify the establishment of infection; and similarly to the control non-bystander mice, parasite clearance was maintained in TR and prevented in TS mice. Therefore, a better comprehension of immunoregulation of innate and adaptive immunity in the early stages of infection is necessary for the development of protocols preventing inflammation and contributing to the elimination of parasites.

Administration, Oral↗
PubMed2006

Mathematical models and lymphatic filariasis control: monitoring and evaluating interventions.

Monitoring and evaluation are crucially important to the scientific management of any mass parasite control programme. Monitoring enables the effectiveness of implemented actions to be assessed and necessary adaptations to be identified; it also determines when management objectives are achieved. Parasite transmission models can provide a scientific template for informing the optimal design of such monitoring programmes. Here, we illustrate the usefulness of using a model-based approach for monitoring and evaluating anti-parasite interventions and discuss issues that need addressing. We focus on the use of such an approach for the control and/or elimination of the vector-borne parasitic disease, lymphatic filariasis.

Animals↗
PubMed2001

[Predacious nematode-destroying fungi].

Gastrointestinal nematodes are considered a serious economic problem affecting the livestock industry around the world. Current methods of their control, relaying mainly on organic drugs, are not sustainable because parasites develop resistance to anthelmintic and bacause of increasing public concern about chemicals residues in livestock products and environment. Nematode-trapping fungi offer a very promissing, nonchemotherapeutic approach to nematode parasite control. Their potential in preventing nematodosis is well documented. In this paper we outline the present knowlege on mechanisms involved in trapping and killing nematodes by the predacious nematode-destroying fungi.

Animals↗
PubMed1999

[TH1 response in the experimental infection with Trypanosoma cruzi].

Specific antibodies and the activation of phagocytic cells by IFN-gamma are the key elements of the immune response involved in protection of the T. cruzi infected host. The central role of the IFN-gamma in vivo seems to be the activation of the inducible nitric oxide synthetase of macrophages (iNOS) and the production of nitric oxide (NO degree) for the intracellular destruction of the parasite. Interleukin 12 (IL-12), the cytokine that stimulates NK cells for IFN-gamma production, seems to trigger the TH1 response in the acute phase. Other cell types, such as lymphocytes Thy-1+CD4-CD8-, CD4+ and CD8+, are also involved in IFN-gamma production. The down regulation of the TH1 response could in part depend on the decrease in the macrophage activation, as a result of the controlled parasite burden, and on the production of IL-10 and transforming growth factor beta (TGF-beta). The protective TH1 immune response seems to be also related to both the tissue damage and the alterations of the immune response observed during the infection. We studied the kinetics of both NK cell activity, and the production of IL-12 and/IFN-gamma by spleen cells, as well as the seric levels of these cytokines, in BALB/c and C3H mice infected with T. cruzi, Tulahuén strain. In the spleen, we found that the production of IL-12 and the NK cell activity increased in the very early acute infection, and that in C3H the effect was higher than in BALB/c mice. IFN-gamma increased in C3H at the same time, but in the BALB/c strain it increased later in the acute phase. The infection induced a very early increase in the seric levels of IL-12, that remained high throughout the acute phase, in both mouse strains. However, the levels of IFN-gamma in the serum increased a few days before the peak of parasitemia, reaching higher values, and earlier, in BALB/c than in C3H mice. Surprisingly, in the chronic infection IL-12 production remained high in both mouse strains, but IFN-gamma production was only observed in BALB/c mice. The immune response was predominantly TH1 in both mouse strains, in spite of the higher susceptibility of BALB/c compared to C3H. The early control of the parasite burden could be evaluated as the expression of the TH1 response in spleen cells, while the seric levels of IL-12 and IFN-gamma would be related to the induction of tissue damage. Our data indicate that the protective TH1 immune response has a different expression according to the host-parasite relationship, and that the factors controlling the response are of primary importance to determine the quali- and quantitative expression of IL-12/NK/IFN-gamma as well as their involvement in resistance and tissue damage.

Animals↗
PubMed1996

Production of dairy replacement stock in relation to level of exposure to gastrointestinal nematode infection in the first grazing season: second-year calves and heifers.

In two experiments, groups of calves which had been exposed to different levels and patterns of infection with Ostertagia and Cooperia spp. in a simulated first grazing season (FGS), were followed throughout a natural second grazing season (SGS). Milk yields in the subsequent first lactation period were also recorded. The results suggest that although there had been differences in immune status among groups, which had been infected in the FGS, prior to the SGS, weight gain among these groups was not significantly different during the SGS. Apparently, resistance to the pathogenic effects of reinfection had developed more strongly and at lower levels of exposure to infection than resistance against establishment of larvae as shown after an experimental challenge. The groups of calves not infected during the FGS did gain less than all other groups during the SGS. Further, infection-induced differences in weight gain among the infected groups in the FGS appeared to be permanent, at least up to the end of the SGS. Finally, first lactation yield was positively correlated with body weight at calving. On average, approximately 10 kg less milk was produced for each kg of lower body weight at calving. With respect to the implications for preventive control strategies in the FGS, it is suggested that parasite control should not be applied beyond a level at which weight gain reduction is prevented.

Animal Feed↗
PubMed2005

Haemonchus contortus: molecular cloning, sequencing, and expression analysis of the gene coding for the small subunit of ribonucleotide reductase.

Gastro-intestinal (GI) parasites are of great agricultural importance, annually costing the livestock industry vast amounts in resources to control parasitism. One such GI parasite, Haemonchus contortus, is principally pathogenic to sheep; with the parasite's blood-feeding behaviour causing effects ranging from mild anaemia to mortality in young animals. Current means of control, which are dependent on repeated treatment with anthelmintic chemicals, have led to increasing drug resistance. Together with the growing concern over residual chemicals in the environment and food chain, this has led to attempts to better understand the biology of the parasite with the aim to develop alternate or supplementary means of control, including the development of molecular vaccines. As a first step towards the understanding of the synthesis of deoxyribonucleotides in H. contortus, and its potential application to therapeutic control of this economically important parasite, we report the cloning, sequencing, and mRNA expression analysis of the ribonucleotide reductase R2 gene.

Amino Acid Sequence↗
PubMed2005

Ex vivo and in vitro impairment of CD36 expression and tumor necrosis factor-alpha production in human monocytes in response to Plasmodium falciparum-parasitized erythrocytes.

Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.

Animals↗