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1.
S Afr Med J ; 110(7): 657-660, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880343

RESUMO

BACKGROUND: The World Health Organization recommends praziquantel (PZQ) (40 mg/kg body weight) for treating schistosomiasis. However, drug failure has been reported, prompting use of 60 mg/kg, for which results have been inconsistent. OBJECTIVES: To compare the efficacy of PZQ 40 mg/kg and 60 mg/kg in treating schoolchildren infected with Schistosoma haematobium. METHODS: The study was conducted during November 2017 - August 2018 in the Ingwavuma area, uMkhanyakude District, KwaZulu-Natal Province, South Africa. Children aged 10 - 15 years were screened for S. haematobium using a filtration technique. Infected children were randomly assigned to a dose of PZQ of 40 mg/kg or 60 mg/kg. Side-effects were recorded within 24 hours after treatment using questionnaires and direct observation. Four weeks after treatment, participants were retested for S. haematobium infection. Baseline and post-treatment mean egg counts were calculated. Cure rate (CR) and egg reduction rate (ERR) were used to determine PZQ efficacy, while repeated-measures analysis of variance determined the effect of both doses on infection intensity. A χ2 test was used to determine the association of side-effects with treatment, with a p-value ≤0.05. RESULTS: Forty-three and 36 children were treated with PZQ 40 mg/kg and 60 mg/kg, respectively. The 40 mg/kg group had a CR of 79.0% and an ERR of 97.2%, and the 60 mg/kg group a CR of 83.0% and an ERR of 98.3%. The effect of dose on infection intensity was not significantly different between the two groups (p>0.05). Abdominal pains, dizziness and fatigue were common among children who received PZQ 40 mg/kg, while headache, dizziness and nausea were common in the 60 mg/kg group. CONCLUSIONS: The efficacy of PZQ at 60 mg/kg was similar to that at 40 mg/kg. A dose >40 mg/kg therefore does not add value in treating S. haematobium infection. Transient side-effects (mostly dizziness) were observed more in the 60 mg/kg group than in the 40 mg/kg group. We recommend continued use of 40 mg/kg body weight for treating schistosomiasis.


Assuntos
Anti-Helmínticos/administração & dosagem , Praziquantel/administração & dosagem , Esquistossomose Urinária/tratamento farmacológico , Dor Abdominal , Adolescente , Animais , Anti-Helmínticos/efeitos adversos , Criança , Tontura , Relação Dose-Resposta a Droga , Doenças Endêmicas , Fadiga , Feminino , Cefaleia , Humanos , Masculino , Náusea , Praziquantel/efeitos adversos , Schistosoma haematobium , África do Sul
2.
Life Sci ; 261: 118458, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961231

RESUMO

AIM: Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetamide-induced hepatocellular carcinoma (HCC) in rats. We evaluated its antitumor effect through regulating Wnt/ß-catenin and Notch signaling pathways and apoptosis. MAIN METHODS: Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/ß-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and ß-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3. KEY FINDING: The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/ß-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation. SIGNIFICANCE: We conclude that NIC acts by inhibiting Wnt/ß-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.


Assuntos
Anti-Helmínticos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niclosamida/uso terapêutico , Receptores Notch/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Anti-Helmínticos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Portadores de Fármacos/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Micelas , Nanopartículas/química , Niclosamida/administração & dosagem , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
3.
PLoS Negl Trop Dis ; 14(9): e0008566, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941434

RESUMO

Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted "cyclic" treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically "off-label", and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent "out-of-stock" situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.


Assuntos
Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Equinococose/tratamento farmacológico , Animais , Echinococcus/efeitos dos fármacos , Echinococcus/fisiologia , Humanos
4.
Korean J Parasitol ; 58(4): 421-430, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32871636

RESUMO

This study aimed to investigate whether mass drug administration (MDA) intervention has an equivalent effect on reducing the prevalence and intensity of Schistosoma haematobium infection regardless of the baseline values. A repeated cross-sectional survey was performed targeting students of 12 primary schools in Al Jabalain and El Salam districts of White Nile State, Sudan, at both 1 week before and 8 months after the MDA. Prior to the baseline survey, school-aged children in Al Jabalain had received MDA interventions twice in 4 years, while those in El Salam had not. The baseline prevalence was 9.1% in Al Jabalain and 35.2% in El Salam, which were reduced to 1.8% and 5.5% at 8 months after the MDA, respectively. The corresponding reduction rates were 80.3% and 84.4%, not significant difference between both districts. However, changes in the geometric mean intensity (GMI) of egg counts were significantly different between both districts. The baseline GMIs were 14.5 eggs per 10 ml of urine (EP10) in Al Jabalain and 18.5 EP10 in El Salam, which were reduced to 7.1 and 11.2 EP10 after treatment, respectively. The corresponding reduction rates were 51.0% and 39.5%. In conclusion, MDA interventions were found to bring about similar relative reduction in prevalence regardless of the baseline value; however, the relative reduction in infection intensity was more salient in the district with a low baseline value for both prevalence and intensity. This clearly points to the importance of repeated MDA interventions in endemic areas, which will eventually contribute to schistosomiasis elimination.


Assuntos
Anti-Helmínticos/administração & dosagem , Administração Massiva de Medicamentos , Esquistossomose Urinária/epidemiologia , Esquistossomose Urinária/prevenção & controle , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Instituições Acadêmicas , Sudão/epidemiologia , Inquéritos e Questionários
5.
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
6.
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
7.
PLoS One ; 15(8): e0236143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790679

RESUMO

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance.


Assuntos
Criação de Animais Domésticos/métodos , Anti-Helmínticos/administração & dosagem , Infecções por Nematoides/veterinária , Doenças dos Ovinos/tratamento farmacológico , Ovinos/parasitologia , Animais , Anti-Helmínticos/farmacocinética , Fazendas , Fezes/parasitologia , Feminino , Meia-Vida , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Ivermectina/farmacocinética , Larva , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Nematoides/isolamento & purificação , Infecções por Nematoides/diagnóstico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Período Pós-Parto , Gravidez , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/parasitologia
8.
Exp Parasitol ; 217: 107938, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768560

RESUMO

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.


Assuntos
Antígenos CD34/sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/terapia , Animais , Anti-Helmínticos/administração & dosagem , Fezes/parasitologia , Sangue Fetal/citologia , Citometria de Fluxo , Granuloma/prevenção & controle , Granuloma/terapia , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Fígado/patologia , Hepatopatias Parasitárias/prevenção & controle , Hepatopatias Parasitárias/terapia , Masculino , Células-Tronco Mesenquimais , Camundongos , Fator 3 de Transcrição de Octâmero , Contagem de Ovos de Parasitas , Praziquantel/administração & dosagem , Coloração e Rotulagem , Fator de Crescimento Transformador beta
9.
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
10.
Parasitol Res ; 119(9): 3099-3104, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627079

RESUMO

The first case of feline ocular Thelazia callipaeda infection and two new canine imported infections in West Germany are here described. The three animals had a history of recent travel to/from other countries. The young adult cat imported from Spain presented an intermittent unilateral ocular discharge. During in-depth ophthalmic examination, a single alive nematode was removed from the conjunctival compartment of the affected eye. Referring to the canine cases, an adult female dog originated from Kenya presented epiphora and mucous whitish-grey discharge of the right eye. During flushing of the nasolacrimal duct two small, thin and long nematodes were removed. Furthermore, a male Borzoi racing dog with regular visit to racing tracks in different countries presented ocular mucous discharge. At ophthalmologic examination, two transparent-whitish vital nematodes were removed. All nematode specimens of the three cases were morphologically identified as adult T. callipaeda parasites. The animals were treated orally with milbemycin oxime (2.0 mg/kg; cat) or milbemycin oxime/praziquantel (0.5 mg/kg and 5.0 mg/kg; dogs) twice with 1-week interval resulting in complete resolution of symptoms. The repeated introduction of patent T. callipaeda-infected animals, especially from southern and eastern endemic countries, will ease the establishment of ophthalmic thelaziosis in Northern Europe. The male fruit fly, Phortica variegata, an intermediate host of T. callipaeda, is endemic within European countries. Considering the clinical and zoonotic relevance of ophthalmic thelaziosis, enhanced disease awareness of European medical and veterinarian doctors and in-depth eye examination for proper detection of T. callipaeda are crucial for appropriate anthelmintic treatments and to limit spreading of the infection.


Assuntos
Doenças do Gato/parasitologia , Doenças do Cão/parasitologia , Infecções Oculares Parasitárias/parasitologia , Infecções por Spirurida/veterinária , Thelazioidea/isolamento & purificação , Animais , Anti-Helmínticos/administração & dosagem , Doenças do Gato/tratamento farmacológico , Gatos , Cães , Infecções Oculares Parasitárias/tratamento farmacológico , Feminino , Alemanha , Macrolídeos/administração & dosagem , Masculino , Infecções por Spirurida/tratamento farmacológico , Infecções por Spirurida/parasitologia , Thelazioidea/genética , Thelazioidea/fisiologia
12.
PLoS One ; 15(6): e0232867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497049

RESUMO

INTRODUCTION: The Neglected Tropical Diseases Roadmap of the WHO set targets for potential elimination as a "public health problem" for the period 2012-2020 in multiple countries in Africa, with the aim of global elimination of schistosomiasis as a "public health problem" by 2025. AIM: The purpose of the study was to estimate the cost from a provider's perspective of the Department of Health's Schistosomiasis Mass Drug Administration (MDA) in Ugu District, KwaZulu-Natal in 2012, with a view to project the costs for the entire KwaZulu Natal Province. METHODS: A total of 491 public schools and 16 independent schools in Ugu District, a predominantly rural district in KwaZulu-Natal with a total of 218 242 learners, were included in the schistosomiasis control programme. They were randomly selected from schools situated below an altitude of 300 meters, where schistosomiasis is endemic. A retrospective costing study was conducted using the provider's perspective to cost. Cost data were collected by reviewing existing records including financial statements, invoices, receipts, transport log books, equipment inventories, and information from personnel payroll, existing budget, and the staff diaries. RESULTS: A total of 15571 children were treated in 2012, resulting in a total cost of the MDA programme of ZAR 2 137 143 and a unit cost of ZAR 137. The three main cost components were Medication Costs (37%), Human Resources Cost (36%) and Capital items (16%). The total cost for treating all eligible pupils in KwaZulu-Natal will be ZAR 149 031 888. However, should the capital cost be excluded, then the unit cost will be ZAR 112 per patient and this will translate to a total cost of ZAR 121 836 288. CONCLUSIONS: Low coverage exacerbates the cost of the programme and makes a decision to support such a programme difficult. However, a normative costing study based on the integration of the programme within the Department of Health should be conducted.


Assuntos
Anti-Helmínticos/economia , Custos Diretos de Serviços/estatística & dados numéricos , Administração Massiva de Medicamentos/economia , Praziquantel/economia , Esquistossomose/tratamento farmacológico , Serviços de Saúde Escolar/economia , Adolescente , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Gastos de Capital/estatística & dados numéricos , Criança , Custos de Medicamentos/estatística & dados numéricos , Doenças Endêmicas/economia , Doenças Endêmicas/prevenção & controle , Feminino , Humanos , Masculino , Folhetos , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Estudos Retrospectivos , População Rural , Amostragem , Esquistossomose/economia , Esquistossomose/epidemiologia , África do Sul/epidemiologia
13.
Lancet Infect Dis ; 20(7): e165-e172, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32595046

RESUMO

Although preventive chemotherapy has been instrumental in reducing schistosomiasis incidence worldwide, serious challenges remain. These problems include the omission of certain groups from campaigns of mass drug administration, the existence of persistent disease hotspots, and the risk of recrudescent infections. Central to these challenges is the fact that the diagnostic tools currently used to establish the burden of infection are not sensitive enough, especially in low-endemic settings, which results in underestimation of the true prevalence of active Schistosoma spp infections. This central issue necessitates that the current schistosomiasis control strategies recommended by WHO are re-evaluated and, possibly, adapted. More targeted interventions and novel approaches have been used to estimate the prevalence of schistosomiasis, such as establishing infection burden by use of precision mapping, which provides high resolution spatial information that delineates variations in prevalence within a defined geographical area. Such information is instrumental in guiding targeted intervention campaigns. However, the need for highly accurate diagnostic tools in such strategies is a crucial factor that is often neglected. The availability of highly sensitive diagnostic tests also opens up the possibility of applying strategies of sample pooling to reduce the cost of control programmes. To interrupt the transmission of, and eventually eliminate, schistosomiasis, better local targeting of preventive chemotherapy, in combination with highly sensitive diagnostic tools, is crucial.


Assuntos
Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Erradicação de Doenças , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Humanos , Administração Massiva de Medicamentos
14.
PLoS Negl Trop Dis ; 14(6): e0008277, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569275

RESUMO

BACKGROUND: Better knowledge of the efficacy and safety of single-dose 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group. METHODOLOGY: We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6-14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs). PRINCIPAL FINDINGS: Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up. CONCLUSIONS/SIGNIFICANCE: There is no indication that single-dose 40 mg/kg oral praziquantel would be less efficacious and less safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety.


Assuntos
Anti-Helmínticos/administração & dosagem , Quimioprevenção/métodos , Praziquantel/administração & dosagem , Esquistossomose Urinária/prevenção & controle , Esquistossomose mansoni/prevenção & controle , Administração Oral , Adolescente , Animais , Anti-Helmínticos/efeitos adversos , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Humanos , Modelos Lineares , Masculino , Contagem de Ovos de Parasitas , Praziquantel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Schistosoma haematobium , Schistosoma mansoni , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Resultado do Tratamento
16.
Trop Doct ; 50(3): 216-221, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356671

RESUMO

Repeated praziquantel treatment for schistosomiasis is an effective method to reduce disease burden. Ultrasonographic methods were used to assess the severity of schistosoma mansoni-related liver disease and demonstrate improvement following treatment. We compared data from 733 children in 2010 and 972 children in 2018 to determine the effect of repeated praziquantel treatment on prevalence of liver disease. Three age groups were compared across three liver disease classifications (normal, mild, severe). From 2010 to 2018, there was a significant reduction in prevalence of severe liver disease in all age groups (P = 0.03 for 5-10 years, P < 0.001 for 11-15 years and 16-20 years). In both male and female students, the proportion having a normal liver significantly increased (P < 0.001) from 2010 to 2018, in the 11-15-year-olds and 16-20-year-olds, demonstrating that liver disease significantly reduced in these age groups. This study demonstrates a reduction in schistosomiasis-related morbidity with repeated praziquantel treatment.


Assuntos
Anti-Helmínticos/administração & dosagem , Hepatopatias Parasitárias/prevenção & controle , Praziquantel/administração & dosagem , Esquistossomose/prevenção & controle , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Humanos , Hepatopatias Parasitárias/diagnóstico por imagem , Hepatopatias Parasitárias/epidemiologia , Hepatopatias Parasitárias/patologia , Masculino , Prevalência , População Rural , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/diagnóstico por imagem , Esquistossomose/epidemiologia , Esquistossomose/patologia , Ultrassonografia , Adulto Jovem , Zâmbia/epidemiologia
17.
Vet Parasitol ; 281: 109121, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32361524

RESUMO

The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ±â€¯0.07 µg/mL and 3.63 ±â€¯1.21 µg.h/mL) compared with those that received ABZ alone (0.45 ±â€¯0.15 µg/mL and 9.50 ±â€¯2.84 µg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.


Assuntos
Albendazol/administração & dosagem , Resistência a Medicamentos/efeitos dos fármacos , Gastroenteropatias/tratamento farmacológico , Helmintíase Animal/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Timol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Quimioterapia Combinada , Gastroenteropatias/parasitologia , Helmintíase Animal/parasitologia , Compostos Fitoquímicos/farmacologia , Ovinos , Doenças dos Ovinos/parasitologia , Resultado do Tratamento
18.
BMC Infect Dis ; 20(1): 323, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375658

RESUMO

BACKGROUND: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. METHODS: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. RESULTS: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. CONCLUSION: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.


Assuntos
Anti-Helmínticos/administração & dosagem , Praziquantel/administração & dosagem , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose Urinária/tratamento farmacológico , Adolescente , Adulto , Alanina Transaminase/sangue , Animais , Anti-Helmínticos/uso terapêutico , Aspartato Aminotransferases/sangue , Estudos de Casos e Controles , Criança , Estudos de Coortes , Esquema de Medicação , Feminino , Gana , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Fígado/efeitos dos fármacos , Fígado/fisiologia , Masculino , Contagem de Ovos de Parasitas , Praziquantel/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
19.
BMC Infect Dis ; 20(1): 376, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460712

RESUMO

BACKGROUND: Despite the existence of a population-based control program using single dose albendazole or mebendazole as a preventive chemotherapy, hookworm transmission remains high. It causes a negative impact on the growth and school performance of children. In connection to this preventive chemotherapy, different studies produced conflicting results. This study aimed at evaluating the efficacy of single (500 mg) versus multiple doses (100 mg twice a day during three consecutive days) of mebendazole against hookworm infections among school-aged children. METHODS: This randomized open-label clinical trial took place among school-aged children (6-14 years old) in Burie and Debre Elias towns, Northwest Ethiopia. Using simple randomization, eligible hookworm-positive children were allocated (1:1) to either a single or multiple dose treatment arms. Stool samples were collected and processed using McMaster method at baseline and follow-up period (14-21 days after treatment). Only laboratory technicians were blinded. The cure and egg reduction rates were the primary and secondary therapeutic outcome measures against hookworm infections, respectively. An independent t-test was used to compare group means, and logistic regression was used to calculate odds ratio (OR). P-value < 0.05 at 95% CI was considered statistically significant. RESULT: One hundred eight children, 54 in each treatment arm had completed baseline data and received allocated treatment. One hundred three children had completed follow-up data records and included for the final efficacy analysis. Cure rate against hookworm was significantly higher in the multiple dose (96.1%) than in the single dose (30.8%) with OR = 55.125; 95% CI: 11.92-254.9; P < 0.001. The egg reduction rate in the multiple dose treatment arm (99.5%) was also significantly higher than in the single dose arm (68.9%) with difference t (101) =5.38; 95% CI 230.95-505.36; P < 0.001. CONCLUSION: The single dose regimen of mebendazole for the treatment of hookworm infections showed poor cure and egg reduction rates, while the multiple doses revealed satisfactory. Although multiple dose regimen administration is a bit more complex than the single dose, we strongly encourage replacing it with multiple dose regimen during deworming programs in hookworm endemic areas. TRIAL REGISTRATION: This trial is retrospectively registered in www.pactr.org, number PACTR201911466695052 on November 26, 2019.


Assuntos
Anti-Helmínticos/administração & dosagem , Infecções por Uncinaria/prevenção & controle , Mebendazol/administração & dosagem , Adolescente , Albendazol/administração & dosagem , Ancylostomatoidea/efeitos dos fármacos , Ancylostomatoidea/fisiologia , Animais , Criança , Pré-Escolar , Protocolos Clínicos , Esquema de Medicação , Etiópia , Feminino , Infecções por Uncinaria/parasitologia , Humanos , Modelos Logísticos , Masculino , Estudantes/estatística & dados numéricos
20.
PLoS Negl Trop Dis ; 14(4): e0007973, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32339185

RESUMO

BACKGROUND: This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana. METHOD: From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence. RESULTS: Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9-4.7) to 19% (114/632; 95% CI = 15.8-22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5-33.5) to 78.3% (409/536; 95% CI = 74.7-81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8-1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7-3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1-2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8-3.5) times more likely to occur in school age children than in adults. Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3-3.2). CONCLUSION: The communities targeted by this study showed a range of Schistosoma prevalence's of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC.


Assuntos
Esquistossomose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Helmínticos/administração & dosagem , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/métodos , Demografia , Transmissão de Doença Infecciosa/prevenção & controle , Fezes/parasitologia , Gana/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Administração Massiva de Medicamentos/métodos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Esquistossomose/prevenção & controle , Urina/parasitologia , Adulto Jovem
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