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1.
PLoS Negl Trop Dis ; 14(9): e0008486, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976501

RESUMO

In most endemic sub-Saharan African countries, repeated infections with soil-transmitted helminth (STH) occur as early as six weeks after the end of mass drug administration (MDA) with albendazole. In this study, we designed a new health educational board game Worms and Ladders and evaluated its potential to complement MDA with albendazole and reduce reinfection rates through the promotion of good hygiene practices among school-aged children. The evaluation employed a randomized control trial (RCT) design. Baseline knowledge, attitude and practices (KAP) relating to STH were obtained using a questionnaire from 372 pupils across six schools in Abeokuta, Nigeria. Schools were randomly assigned into intervention and control group, with the former and latter receiving Worms and Ladders and the common Snake and Ladder board game respectively. Fresh stool samples were also collected at baseline for STH diagnosis before administering 400mg single dose albendazole. Follow-up assessments of STH burden and KAP were conducted three and six months' post-intervention. Data generated from the study were analyzed using SPSS 20.0 software, with confidence interval set at 95%. Prevalence of STH dropped from 25.0% to 10.4% in the intervention group and 49.4% to 33.3% in the control group at three months' post-intervention. The prevalence further dropped to 5.6% in the intervention group at six months' post-intervention. However, it increased to 37.2% in the control group at six months' post-intervention. There was a significant difference (p<0.05) in prevalence after intervention among the groups. KAP on transmission, control and prevention of STH significantly improved (p<0.05) from 5.2% to 97.9% in the intervention group compared to 6.2% to 7.1% in the control group. The Worms and Ladders board game shows the potential to teach and promote good hygiene behavior among SAC. These findings posit the newly developed game as a reliable tool to complement mass drug administration campaigns for STH control.


Assuntos
Jogos Recreativos , Educação em Saúde/métodos , Helmintíase/prevenção & controle , Adolescente , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Helmintíase/tratamento farmacológico , Humanos , Masculino , Administração Massiva de Medicamentos , Nigéria/epidemiologia , Prevalência , Instituições Acadêmicas
2.
BMC Infect Dis ; 20(1): 718, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993559

RESUMO

BACKGROUND: Schistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants. METHODS: A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time. DISCUSSION: The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines. TRIAL REGISTRATION: The registration number of this study is NCT03779347 ( clinicaltrials.gov , date of registration: 19 December 2018).


Assuntos
Antígenos de Helmintos/análise , Testes Imunológicos/métodos , Schistosoma haematobium/imunologia , Esquistossomose Urinária/diagnóstico , Esquistossomose Urinária/epidemiologia , Animais , Anti-Helmínticos/uso terapêutico , Pré-Escolar , Estudos Transversais , Confiabilidade dos Dados , Feminino , Seguimentos , Gabão/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Praziquantel/uso terapêutico , Gravidez , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma haematobium/genética , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/parasitologia
3.
PLoS Negl Trop Dis ; 14(9): e0008649, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976496

RESUMO

Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual's response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug-drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver's capacity to metabolise PZQ and observed drug-drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ's metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver's capacity to metabolise PZQ as well as drug-drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans.


Assuntos
Anti-Helmínticos/uso terapêutico , Praziquantel/uso terapêutico , Esquistossomose/tratamento farmacológico , Animais , Anti-Helmínticos/farmacocinética , Modelos Animais de Doenças , Humanos , Praziquantel/farmacocinética , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Esquistossomose/parasitologia
4.
PLoS Negl Trop Dis ; 14(9): e0008619, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32966290

RESUMO

BACKGROUND: Despite the reported success in reducing morbidity, praziquantel alone is insufficient for the control and elimination of schistosomiasis, partly due to its poor efficacy against the juvenile worms. Artemisinin derivatives are effective against juvenile worms but are less effective against adult worms. We compared the safety and efficacy of praziquantel and Dihydroartemisinin-piperaquine combination against the standard praziquantel alone for treatment of intestinal schistosomiasis. METHODS: In this randomized, open-label, non-inferiority trial, 639 Schistosoma mansoni infected children were enrolled and randomized to receive either praziquantel alone or praziquantel plus Dihydroartemisinin-piperaquine combination. Two stool samples were collected on consecutive days at baseline, 3 and 8 weeks post-treatment and analyzed using thick smear Kato Katz method. Efficacy was assessed by cure and egg reduction rates at 3 and 8 weeks post-treatment. Adverse events were assessed within four hours of drugs intake. The primary outcome was cure rates at 8 weeks of post-treatment. Secondary outcomes were egg reduction rates at 8 weeks of post-treatment and treatment-associated adverse events. RESULTS: At 3 weeks of post-treatment, cure rates were 88.3% (263/298, 95% CI = 84.1%- 91.4%) and 81.2% (277/341, 95% CI = 76.7%- 85.0%) for the combination therapy and praziquantel alone, respectively (p < 0.01, odds ratio (OR) = 1.74, 95% CI of OR = 1.11 to 2.69). At 8 weeks, there was a significant drop in the cure rates in praziquantel alone group to 63.9% (218/341, 95% CI = 58.7%- 68.8%) compared to 81.9% (244/298, 95% CI = 77.1%- 85.8%) in the combination therapy group (p < 0.0001, OR = 2.55, 95%CI of OR = 1.75 to 3.69). Egg reduction rates at 8 weeks post-treatment were significantly higher in the combination therapy group 93.6% (95% CI = 90.8%- 96.4%) compared to 87.9% (95% CI = 84.4%- 91.4%) in the praziquantel only group (p = 0.01). On both Univariate and Multivariate regression analysis, type of treatment received was a significant predictor of cure at week 8 post-treatment. Overall, 30.8% (95% CI = 27.2%- 34.4%) of the study participants experienced mild and transient treatment-associated adverse events, post-treatment abdominal pain (27.1%) being the most common adverse event observed. There was no significant difference in the overall occurrence of adverse events between the two treatment groups. CONCLUSION: Praziquantel and Dihydroartemisinin piperaquine combination therapy is safe, and more efficacious compared to praziquantel alone for the treatment of intestinal schistosomiasis. Further studies are needed to explore if the combination therapy can be considered as an option for mass drug administration to control and eventually eliminate schistosomiasis.


Assuntos
Anti-Helmínticos/uso terapêutico , Artemisininas/uso terapêutico , Praziquantel/uso terapêutico , Quinolinas/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Adolescente , Animais , Anti-Helmínticos/efeitos adversos , Artemisininas/efeitos adversos , Criança , Quimioterapia Combinada , Fezes/parasitologia , Feminino , Humanos , Intestinos/parasitologia , Masculino , Praziquantel/efeitos adversos , Quinolinas/efeitos adversos , Schistosoma mansoni/efeitos dos fármacos , Tanzânia , Resultado do Tratamento
5.
Infect Dis Poverty ; 9(1): 121, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867849

RESUMO

BACKGROUND: Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed. METHODS: During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations. RESULTS: In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by 'positive' urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% confidence interval [CI]: 27.5-35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (relative risk [RR] = 1.7, 95% CI: 1.4-2.2) and Mchoka (RR = 2.7, 95% CI: 1.7-4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0 to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI: 20.3-27.7). CONCLUSIONS: We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control.


Assuntos
Surtos de Doenças , Esquistossomose Urinária/epidemiologia , Esquistossomose mansoni/epidemiologia , Anti-Helmínticos/uso terapêutico , Criança , Estudos Transversais , Humanos , Lagos , Malaui/epidemiologia , Morbidade , Praziquantel/uso terapêutico , Prevalência , Fatores de Risco , Esquistossomose Urinária/complicações , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose mansoni/complicações , Esquistossomose mansoni/tratamento farmacológico , Instituições Acadêmicas
6.
Exp Parasitol ; 218: 107980, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32877640

RESUMO

Acacia farnesiana pods are rich in secondary metabolites and their biological activities have been recorded as antibacterial, antioxidant and anthelmintic. Previously, an in vitro bioguided study showed the important ovicidal and larvicidal effects of an organic fraction (EtOAc-F) from a hydroalcoholic extract of A. farnesiana pods against Haemonchus contortus. The present study aimed to assess the in vivo anthelmintic effect of EtOAc-F from A. farnesiana pods on the H. contortus faecal egg elimination in female lambs and on the infective larvae (L3) population reduction in coprocultures. The EtOAc-F was obtained from a hydroalcoholic extract from A. farnesiana pods through chromatographic procedures; additionally, some secondary compounds were identified using high-performance liquid chromatography (HPLC). Twenty-one 'Katahdin' crossbred female lambs ranging from three to four months of age, with body weights 21.9 ± 0.39 kg were used. Animals were orally infected with H. contortus (L3) by a single dose of 350 L3/kg BW. Three experimental groups (n = 7) were assigned as follows: 1) Control (untreated), 2) Albendazole, as a positive control (at 7.5 mg/kg BW, unique dose) and 3) EtOAc-F (at 100 mg/kg BW, once every third day, with three applications in total). Individual faecal samples were collected once a week for 5 weeks (at days 38, 45, 52, 59 and 66) post-treatment, to measure the faecal egg counts (FEC) and to obtain the H. contortus (L3) population from faecal cultures. The highest FEC reduction caused by EtOAc-F was 67.7%; meanwhile, albendazole showed a total FEC reduction after the second week post-treatment (day 45). On the other hand, the fraction caused an important reduction in the larval population in coprocultures (54.3-68.5%). The phytochemical analysis revealed the presence of galloyl derivatives and flavonoids as major compounds. The A. farnesiana pods could serve as a natural anthelmintic for the control of H. contortus, and perhaps for controlling other parasites of veterinary importance.


Assuntos
Acacia/química , Anti-Helmínticos/uso terapêutico , Hemoncose/veterinária , Extratos Vegetais/uso terapêutico , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Fezes/parasitologia , Feminino , Flavonoides/química , Ácido Gálico/química , Hemoncose/tratamento farmacológico , Hemoncose/parasitologia , Haemonchus/efeitos dos fármacos , Haemonchus/isolamento & purificação , Hematócrito/veterinária , Contagem de Ovos de Parasitas/veterinária , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/parasitologia
8.
BMC Infect Dis ; 20(1): 691, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957922

RESUMO

BACKGROUNDS: The incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests. CASE PRESENTATION: A 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations. CONCLUSIONS: The case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.


Assuntos
Angiostrongylus cantonensis/genética , Helmintíase do Sistema Nervoso Central/parasitologia , Sequenciamento de Nucleotídeos em Larga Escala , Infecções por Strongylida/parasitologia , Adulto , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Helmintíase do Sistema Nervoso Central/tratamento farmacológico , Helmintíase do Sistema Nervoso Central/etiologia , Líquido Cefalorraquidiano/parasitologia , Humanos , Masculino , Metagenoma , Metilprednisolona/uso terapêutico , Reação em Cadeia da Polimerase , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/etiologia
9.
PLoS Negl Trop Dis ; 14(8): e0008551, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804925

RESUMO

BACKGROUND: The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation. METHODOLOGY: We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses. PRINCIPAL FINDINGS: We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries. CONCLUSIONS AND SIGNIFICANCE: Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.


Assuntos
Demografia , Inquéritos Epidemiológicos , Organização Mundial da Saúde , Anti-Helmínticos/uso terapêutico , Burundi , Pré-Escolar , Bases de Dados Factuais , Feminino , Helmintíase/transmissão , Humanos , Lactente , Masculino , Mianmar , Filipinas
10.
PLoS Negl Trop Dis ; 14(8): e0008600, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853225

RESUMO

Helminth infections are among the World Health Organization's top neglected diseases with significant impact in many Less Economically Developed Countries. Despite no longer being endemic in Europe, the widespread presence of helminth eggs in archaeological deposits indicates that helminths represented a considerable burden in past European populations. Prevalence of infection is a key epidemiological feature that would influence the elimination of endemic intestinal helminths, for example, low prevalence rates may have made it easier to eliminate these infections in Europe without the use of modern anthelminthic drugs. To determine historical prevalence rates we analysed 589 grave samples from 7 European sites dated between 680 and 1700 CE, identifying two soil transmitted nematodes (Ascaris spp. and Trichuris trichiura) at all locations, and two food derived cestodes (Diphyllobothrium latum and Taenia spp.) at 4 sites. The rates of nematode infection in the medieval populations (1.5 to 25.6% for T. trichiura; 9.3-42.9% for Ascaris spp.) were comparable to those reported within modern endemically infected populations. There was some evidence of higher levels of nematode infection in younger individuals but not at all sites. The genetic diversity of T. trichiura ITS-1 in single graves was variable but much lower than with communal medieval latrine deposits. The prevalence of food derived cestodes was much lower (1.0-9.9%) than the prevalence of nematodes. Interestingly, sites that contained Taenia spp. eggs also contained D. latum which may reflect local culinary practices. These data demonstrate the importance of helminth infections in Medieval Europe and provide a baseline for studies on the epidemiology of infection in historical and modern contexts. Since the prevalence of medieval STH infections mirror those in modern endemic countries the factors affecting STH decline in Europe may also inform modern intervention campaigns.


Assuntos
Helmintíase/epidemiologia , Intestinos/parasitologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Helmínticos/uso terapêutico , Ascaríase/epidemiologia , Ascaríase/transmissão , Ascaris , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Variação Genética , Helmintíase/tratamento farmacológico , Helmintíase/transmissão , Helmintos/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/epidemiologia , Nematoides , Prevalência , Solo/parasitologia , Toaletes , Tricuríase/epidemiologia , Tricuríase/transmissão , Trichuris , Adulto Jovem
11.
Am J Trop Med Hyg ; 103(4): 1590-1592, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32830642

RESUMO

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.


Assuntos
Infecções por Coronavirus/parasitologia , Diabetes Mellitus/parasitologia , Hipertensão/parasitologia , Doenças do Sistema Nervoso Periférico/parasitologia , Pneumonia Viral/parasitologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/parasitologia , Corticosteroides/administração & dosagem , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus/patogenicidade , Coinfecção , Connecticut , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/virologia , Equador , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/virologia , Fatores Imunológicos/administração & dosagem , Masculino , Pandemias , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Estrongiloidíase/virologia
12.
PLoS Negl Trop Dis ; 14(8): e0008494, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32833994

RESUMO

Helminth control at the national level is currently based on mass drug administration (MDA) programs. Perception of the MDA programs for helminth control by the affected populations influences compliance and future designs of the programs. We determined the perception of Zimbabwe's National Helminth Control Program (2012-2017) with a specific focus on schistosomiasis in the school children treated with praziquantel, schoolteachers and village health workers (VHW). The study enrolled 409 children from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017. Thirty-six schoolteachers and 22 VHW serving the schools were also recruited. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to the children and the adults. The questions focused on the perceived impact on health, school attendance and performance and Knowledge Attitudes and Practice (KAP) among the school children. Data were captured electronically on android platforms using the Open Data Kit. Overall, 84% of the children responded that their awareness of schistosomiasis (transmission, disease, treatment and infection avoidance) had improved because of participating in the MDAs. Of the 151 children self-diagnosed with schistosomiasis, 74% reported that their health had improved following treatment with praziquantel. This included resolution of haematuria, painful urination, sore stomach, tiredness and falling asleep during class lessons. The children and teachers reported improvements in both pupil school attendance and performance at school while the VHW and teachers reported an increase in health-seeking behaviour amongst the school children for schistosomiasis treatment in-between MDAs. The majority of VHW (96%) reported improvement in handwashing behaviour, schistosomiasis awareness (96%) and treatment uptake (91%) within the communities where the school children belonged. However, only 59% of the VHW reported improvement in toilet use while only 50% of the VHW reported improvement in clean water use within their communities. This study indicated that the surveyed children perceived the MDA program had improved their health, school attendance, school performance and awareness of schistosomiasis. The VHW also perceived that the MDA program had improved the community KAP.


Assuntos
Albendazol/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Administração Massiva de Medicamentos , Praziquantel/uso terapêutico , Esquistossomose/prevenção & controle , Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Criança , Serviços de Saúde Comunitária , Feminino , Humanos , Masculino , Praziquantel/administração & dosagem , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Instituições Acadêmicas , Zimbábue/epidemiologia
13.
PLoS Negl Trop Dis ; 14(8): e0008473, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841228

RESUMO

Despite growing evidence that infants and very young children can be infected with schistosomes, the epidemiological features and risk factors are not well described in this age group. We aimed to assess the prevalence of S. mansoni infection in children under two years of age from a population with a known high burden of infection in school-aged children and adults and thus inform the need for interventions in this potentially vulnerable age group. In a cross-sectional study in Mbita Sub-county, along the east coast of Lake Victoria, Western Kenya, we enrolled 361 children aged 6-23 months. The prevalence of S. mansoni infection was detected using the Kato-Katz stool examination and a point-of-care test for urinary circulating cathodic antigen (POC-CCA) (Rapid Medical Diagnostics, Pretoria, South Africa). Three-hundred and five (305) children had complete data of whom 276 (90.5%, 95%CI: 86.6-93.5) children were positive for S. mansoni by the POC-CCA test, while 11 (3.6%, 95%CI: 1.8-6.4) were positive by the Kato-Katz method. All Kato-Katz positive cases were also positive by the POC-CCA test. In multivariable analysis, only geographical area, Rusinga West (AOR = 7.1, 95%CI: 1.4-35.2, P = 0.02), was associated with S. mansoni infection using Kato-Katz test. Independent associations for POC-CCA positivity included age, (12-17 months vs 6-11 months; AOR = 7.8, 95%CI: 1.8-32.6, P = 0.002) and breastfeeding in the previous 24 hours (AOR = 3.4, 95%CI: 1.3-9.0, P = 0.009). We found a potentially very high prevalence of S. mansoni infection among children under two years of age based on POC-CCA test results in Mbita Sub-county, Kenya, which if confirmed strongly supports the need to include infants in public health strategies providing universal prophylactic treatment in high burden settings. Further research is required to determine the accuracy of diagnostic tools to detect light infection among very young children and possible long-term health impacts.


Assuntos
Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/parasitologia , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Feminino , Humanos , Lactente , Quênia/epidemiologia , Masculino , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Prevalência , Fatores de Risco , Esquistossomose mansoni/prevenção & controle
14.
PLoS Negl Trop Dis ; 14(8): e0008505, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776942

RESUMO

Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low- and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infections, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infections, resulting in an important reduction in STH-attributable morbidity in children, while additional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved.


Assuntos
Anti-Helmínticos/uso terapêutico , Saúde Global/tendências , Helmintíase/prevenção & controle , Solo/parasitologia , Organização Mundial da Saúde , Anti-Helmínticos/administração & dosagem , Humanos , Fatores Socioeconômicos
15.
Life Sci ; 258: 118189, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781060

RESUMO

Origin of drug and radio-refractory clones, cancer stem-like cells, and rapid angiogenesis and metastasis are among the primary concerns that limit the efficacy of anticancer treatments, emphasizing the urgency of developing new therapeutics. Factors like high attrition rates, huge investments, patients' heterogeneity, and diverse molecular subtypes have challenged the rapid development of anticancer drugs. Treatment with repurposing pleiotropic benzimidazole antihelminthics, like mebendazole, albendazole, and flubendazole has recently opened a new window, owing to their easy access, low cost as a generic drug, and long track record of safe use in the human population. This review highlights the outcomes of preclinical and clinical studies of these drugs as a potent anticancer agent(s) conducted in the last two decades. Substantial preclinical studies, as well as limited clinical trials, suggest noteworthy anticancer potency of these pleiotropic benzimidazoles, particularly as potent microtubule disrupting, anti-angiogenic, and anti-metastatic agents, inhibitors of the immune checkpoint, hypoxia-inducible factor, epithelial-mesenchymal transition, cancer stemness, and multidrug resistance protein 1, and inducers of apoptosis and M1 polarization. These anticancer effects are attributed to multiple action points, including intrinsic apoptosis, canonical Wnt/ß-catenin, JAK/STAT-3, JNK, MEK/ERK, and hedgehog signaling pathways. The effective anticancer properties of mebendazole, albendazole, and flubendazole either alone or synergistically with frontline drugs, warrant their validation through controlled clinical trials to use them as promising avenues to anticancer therapy.


Assuntos
Anti-Helmínticos/uso terapêutico , Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Reposicionamento de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Humanos
17.
BMC Infect Dis ; 20(1): 470, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615937

RESUMO

BACKGROUND: Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis. Digestive symptoms such as diarrhea and abdominal pain are the main manifestation, but serious infections such as septicemia, purulent meningitis, and bacterial pneumonia may occur in individuals harboring human T-lymphotropic virus type 1 (HTLV-1) or who are immunocompromised. Although coinfection with Strongyloides stercoralis and HTLV-1 can lead to chronic strongyloidiasis and a disseminated form of the disease, there is a high rate of response to the anthelmintic ivermectin. CASE PRESENTATION: We report a case of strongyloidiasis infection syndrome that was difficult to differentiate from immune reconstitution inflammatory syndrome (IRIS) for various reasons. The patient had been treated with the corticosteroids tacrolimus (Tac) and mycophenolate mofetil (MMF) for systemic lupus erythematosus (SLE) with lupus nephritis and pancytopenia. When the steroid was reduced, she developed cytomegalovirus (CMV) enteritis, and her respiratory status rapidly deteriorated immediately after the withdrawal of Tac and MMF. It was difficult to distinguish immune reconstitution inflammatory syndrome from strongyloidiasis infection syndrome because stool cultures were negative and eosinophils were not increased. Bronchoscopy revealed viable Strongyloides, leading to a diagnosis of strongyloidiasis infection syndrome, but the patient died despite treatment. CONCLUSIONS: Both corticosteroid therapy and HTLV-1 infection can be associated with a decrease of eosinophils, despite the presence of parasitic infection. In conclusion, even if multiple culture tests are negative, the risk of parasitic infection should be assessed in patients receiving immunosuppressants and steroids even in non-endemic areas.


Assuntos
Infecções por Citomegalovirus/complicações , Citomegalovirus/imunologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Evolução Fatal , Feminino , Ganciclovir/uso terapêutico , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/tratamento farmacológico , Infecções por HTLV-I/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Ivermectina/uso terapêutico , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologia , Síndrome
18.
PLoS Negl Trop Dis ; 14(7): e0008427, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628671

RESUMO

A major impediment to eliminate lymphatic filariasis and onchocerciasis is the lack of effective short-course macrofilaricidal drugs or regimens that are proven to be safe for both infections. In this study we tested oxfendazole, an anthelmintic shown to be well tolerated in phase 1 clinical trials. In vitro, oxfendazole exhibited modest to marginal motility inhibition of adult worms of Onchocerca gutturosa, pre-adult worms of Onchocerca volvulus and Onchocerca lienalis microfilariae. In vivo, five days of oral treatments provided sterile cure with up to 100% macrofilaricidal efficacy in the murine Litomosoides sigmodontis model of filariasis. In addition, 10 days of oral treatments with oxfendazole inhibited filarial embryogenesis in patent L. sigmodontis-infected jirds and subsequently led to a protracted but complete clearance of microfilaremia. The macrofilaricidal effect observed in vivo was selective, as treatment with oxfendazole of microfilariae-injected naïve mice was ineffective. Based on pharmacokinetic analysis, the driver of efficacy is the maintenance of a minimal efficacious concentration of approximately 100 ng/ml (based on subcutaneous treatment at 25 mg/kg in mice). From animal models, the human efficacious dose is predicted to range from 1.5 to 4.1 mg/kg. Such a dose has already been proven to be safe in phase 1 clinical trials. Oxfendazole therefore has potential to be efficacious for treatment of human filariasis without causing adverse reactions due to drug-induced microfilariae killing.


Assuntos
Benzimidazóis/farmacologia , Filariose Linfática/tratamento farmacológico , Filarioidea/efeitos dos fármacos , Animais , Anti-Helmínticos/uso terapêutico , Modelos Animais de Doenças , Filariose Linfática/parasitologia , Feminino , Filarioidea/embriologia , Gerbillinae/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microfilárias/efeitos dos fármacos , Onchocerca/efeitos dos fármacos , Onchocerca volvulus/efeitos dos fármacos , Oncocercose/tratamento farmacológico
19.
Parasitol Res ; 119(8): 2371-2382, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32607709

RESUMO

After almost 50 years of praziquantel (PZQ) research, Park and Marchant (Trends Parasitol 36:182-194, 2020) described the Ca++-permeable transient receptor potential (TRP) channel Sm.TRPMPZQ in Schistosoma mansoni as target of PZQ. Here we describe the deadly cascade in schistosomes which is induced by the (R)-PZQ enantiomer that includes contemporaneous stereoselective activation of Sm.TRPMPZQ-mediated Ca++ influx, disturbed Ca++ homeostasis, Ca++-dependent spastic paralysis, and Ca++- and PZQ-dependent disruption of parasitic teguments. Under normal conditions, there is a reversible balance between bilayer, isotropic, and HII phases in biological membranes (Jouhet 2013). In vitro, we could observe an irreversible but not stereoselective transition to the HII phase in liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS), two naturally occurring phospholipids in schistosomes, by the concerted action of Ca++ and PZQ (Harder 2013). HII structures are a prerequisite for induction of fusion processes (Jouhet 2013), which, indeed, become visible as blebs, vacuolation processes, and large balloon-like surface exudates in a large variety of PZQ-sensitive parasitic flukes and cestodes after PZQ treatment. These tegument damages are irreversible. As homologs of Sm.TRPMPZQ are also present in the other trematodes S. japonicum, S. haematobium, or Clonorchis sinensis and cestodes Taenia solium, Echinococcus multilocularis, or Hymenolepis microstoma (Park and Marchant, Trends Parasitol 36:182-194, 2020), it is suggested that a similar deadly cascade will be operating generally in PZQ-sensitive parasites.


Assuntos
Cestoides/efeitos dos fármacos , Praziquantel/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Trematódeos/efeitos dos fármacos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Canais de Cátion TRPM/efeitos dos fármacos
20.
Medicine (Baltimore) ; 99(22): e20226, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481388

RESUMO

RATIONALE: Sparganosis is an infectious disease caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissues. Pulmonary and pleural involvement due to sparganum has been rarely reported previously. PATIENT CONCERNS: We herein described a case of recurrent eosinophilic pleuritis in a 24-year-old woman. She was admitted with persistent cough and shortness of breath for more than 1 month. Initial chest computed tomography scan suggested right pleural effusion and diffuse pleural thickening. Slightly elevated eosinophil counts were found in both the peripheral blood and pleural fluid. She underwent right pleurectomy but histological examination failed to obtain an etiological diagnosis. Moreover, eosinophilic pleural effusion re-appeared in the contralateral thoracic cavity one month later. After re-admission, we reviewed her medical history meticulously and found she had a history of ingesting raw snake gallbladders before hospitalization. The final diagnosis was confirmed by the markedly positive reaction against sparganum antigen in both serum and pleural fluid sample. DIAGNOSIS: Eosinophilic pleuritis caused by sparganum infection. INTERVENTIONS: After the diagnosis, the patient was treated with praziquantel at 75 mg/kg/d for 3 days. OUTCOMES: Pleural effusion absorbed completely and eosinophil count in peripheral blood returned to normal range. No evidence of recurrent pleural effusion had been observed in over one year of follow-up. LESSONS: Clinicians need to be aware the possibility of sparganum infection in cases of eosinophilic pleuritis. The specific enzyme-linked immunosorbent assay remains a useful method in acquiring a rapid diagnosis, especially when histological examination is unable to detect the larvae in the thoracic cavity.


Assuntos
Eosinofilia/parasitologia , Pleurisia/parasitologia , Esparganose/diagnóstico , Anti-Helmínticos/uso terapêutico , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Eosinofilia/tratamento farmacológico , Feminino , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Pleurisia/tratamento farmacológico , Praziquantel/uso terapêutico , Recidiva , Esparganose/tratamento farmacológico , Adulto Jovem
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