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1.
Bull World Health Organ ; 102(4): 265-275, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562204

RESUMO

Objective: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. Methods: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.


Assuntos
Esquistossomose , Criança , Adulto , Humanos , Côte d'Ivoire/epidemiologia , Prevalência , Teorema de Bayes , Quênia/epidemiologia , Tanzânia/epidemiologia , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Fezes
2.
Sex Transm Dis ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687328

RESUMO

ABSTRACT: We determined the in vitro minimum lethal concentration (MLC) of secnidazole (SEC) and assessed correlation with clinical susceptibility among T. vaginalis isolates obtained from 71 women, of whom 66 were successfully treated with this medication. An MLC ≤12.5 µg/ml correlated with clinical susceptibility in this study.

3.
Clin Infect Dis ; 76(3): e849-e856, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35639875

RESUMO

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. RESULTS: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Humanos , Masculino , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Sêmen , Libéria/epidemiologia , Estudos Retrospectivos , Antígenos HLA-C , Sobreviventes , Fatores de Risco
4.
Sex Transm Dis ; 50(6): 370-373, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36849257

RESUMO

BACKGROUND: The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined. We conducted a study using T. vaginalis isolates from women with reported treatment success or failure to determine these values. METHODS: We measured MLCs of 47 isolates obtained from women who had failed metronidazole treatment, 33 isolates from women who had failed tinidazole treatment, and 48 isolates from women successfully cured with metronidazole. The cutoff was calculated as the 95th percentile of MLCs of susceptible isolates for each drug. RESULTS: Our data confirmed that the MLC previously associated with metronidazole treatment failure is ≥50 µg/mL and identified the MLC associated with tinidazole treatment failure as ≥6.3 µg/mL. For metronidazole, the agreement between laboratory result and treatment outcome was 93.7%; for tinidazole, this agreement was 88.9%. CONCLUSIONS: The T. vaginalis susceptibility assay is useful for determining whether 5-nitroimidazole treatment failure in persons with trichomoniasis can be attributed to drug resistance. These results are useful for establishing interpretive guidance of test results, and MLC levels can help guide appropriate patient treatment.


Assuntos
Tricomoníase , Vaginite por Trichomonas , Trichomonas vaginalis , Feminino , Humanos , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Tinidazol/uso terapêutico , Vaginite por Trichomonas/tratamento farmacológico , Preparações Farmacêuticas , Resistência a Medicamentos , Tricomoníase/tratamento farmacológico , Falha de Tratamento , Técnicas In Vitro
5.
Proc Natl Acad Sci U S A ; 117(37): 23174-23181, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868437

RESUMO

Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs.


Assuntos
Formação de Anticorpos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose/imunologia , Animais , Pré-Escolar , Fezes/parasitologia , Feminino , Humanos , Lactente , Quênia , Masculino , Prevalência , Esquistossomose/parasitologia , Esquistossomose mansoni/parasitologia
6.
Clin Infect Dis ; 74(Suppl_2): S152-S161, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416973

RESUMO

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.


Assuntos
Infecções por HIV , Nascimento Prematuro , Infecções Sexualmente Transmissíveis , Tricomoníase , Vaginite por Trichomonas , Trichomonas vaginalis , Centers for Disease Control and Prevention, U.S. , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recém-Nascido , Masculino , Metronidazol/uso terapêutico , Gravidez , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Infecções Sexualmente Transmissíveis/epidemiologia , Tricomoníase/diagnóstico , Tricomoníase/tratamento farmacológico , Tricomoníase/epidemiologia , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/tratamento farmacológico , Vaginite por Trichomonas/epidemiologia , Estados Unidos/epidemiologia
7.
J Immunol ; 201(1): 124-133, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29752313

RESUMO

Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guérin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated. Gene ontology pathway analysis identified inhibition of IFN-γ signaling, cellular proliferation, and the Th1 pathway. Targeted real-time quantitative PCR after methyl-specific endonuclease digestion confirmed DNA hypermethylation of the transcription factors BATF3, ID2, STAT5A, IRF5, PPARg, RUNX2, IRF4, and NFATC1 and cytokines or cytokine receptors IFNGR1, TNFS11, RELT (TNF receptor), IL12RB2, and IL12B (p < 0.001; Sidak-Bonferroni). Functional blockage of the IFN-γ signaling pathway was confirmed, with helminth-infected individuals having decreased upregulation of IFN-γ-inducible genes (Mann-Whitney p < 0.05). Hypomethylation of the IL-4 pathway and DNA hypermethylation of the Th1 pathway was confirmed by Ag-specific multidimensional flow cytometry demonstrating decreased TB-specific IFN-γ and TNF and increased IL-4 production by CD4+ T cells (Wilcoxon signed-rank p < 0.05). In S. haematobium-infected individuals, these DNA methylation and immune phenotypic changes persisted at least 6 mo after successful deworming. This work demonstrates that helminth infection induces DNA methylation and immune perturbations that inhibit TB-specific immune control and that the duration of these changes are helminth specific.


Assuntos
Ascaríase/imunologia , Ascaris lumbricoides/imunologia , Vacina BCG/imunologia , Metilação de DNA/genética , Schistosoma haematobium/imunologia , Esquistossomose/imunologia , Células Th1/imunologia , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/biossíntese , Interleucina-4/genética , Receptores de Citocinas/genética , Fatores de Transcrição/genética , Tuberculose/imunologia
8.
Parasitology ; 147(13): 1383-1391, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32729451

RESUMO

BACKGROUND: Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance. METHODS: PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded. RESULTS: The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2-9.6%) than TDZ (0-2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations. DISCUSSION: 5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.


Assuntos
Antiprotozoários/farmacologia , Resistência a Medicamentos , Metronidazol/farmacologia , Tinidazol/farmacologia , Trichomonas vaginalis/efeitos dos fármacos
9.
Clin Infect Dis ; 69(12): 2170-2176, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30768180

RESUMO

BACKGROUND: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kilo-base pair (kbp), double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine the TVV prevalence in US Trichomonas vaginalis isolates and TVV's associations with patient demographics, clinical outcomes, and metronidazole resistance. METHODS: Archived T. vaginalis isolates from the enrollment visits of 355 women participating in a T. vaginalis treatment trial in Birmingham, Alabama, were thawed and grown in culture. Their total RNA was extracted using a Trizol reagent. Contaminating, single-stranded RNA was precipitated using 4.0 M Lithium Chloride and centrifugation. The samples were analyzed by gel electrophoresis to visualize a 4.5 kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates obtained from the women's test of cure visits. RESULTS: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV-positive (TVV+) isolates were significantly older (P = .01), more likely to smoke (P = .04), and less likely to report a history of gonorrhea (P = .04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infections with TVV+ isolates (P = .14 and P = .44, respectively). Of 25 test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance, while 2/15 TVV-negative isolates demonstrated mild to moderate resistance (P = .23). CONCLUSIONS: Of 355 T. vaginalis isolates tested for TVV, T. vaginalis isolates tested for TVV, the prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be commensal to T. vaginalis.


Assuntos
Coinfecção , Infecções por Vírus de RNA/epidemiologia , Infecções por Vírus de RNA/virologia , Vírus de RNA , Vaginite por Trichomonas/epidemiologia , Vaginite por Trichomonas/microbiologia , Trichomonas vaginalis/virologia , Adulto , Resistência a Medicamentos , Feminino , Humanos , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Testes de Sensibilidade Parasitária , Avaliação de Resultados da Assistência ao Paciente , Vigilância em Saúde Pública , Infecções por Vírus de RNA/diagnóstico , Vírus de RNA/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/tratamento farmacológico , Adulto Jovem
10.
MMWR Morb Mortal Wkly Rep ; 67(25): 701-706, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29953425

RESUMO

Outbreaks associated with untreated recreational water can be caused by pathogens, toxins, or chemicals in fresh water (e.g., lakes, rivers) or marine water (e.g., ocean). During 2000-2014, public health officials from 35 states and Guam voluntarily reported 140 untreated recreational water-associated outbreaks to CDC. These outbreaks resulted in at least 4,958 cases of disease and two deaths. Among the 95 outbreaks with a confirmed infectious etiology, enteric pathogens caused 80 (84%); 21 (22%) were caused by norovirus, 19 (20%) by Escherichia coli, 14 (15%) by Shigella, and 12 (13%) by Cryptosporidium. Investigations of these 95 outbreaks identified 3,125 cases; 2,704 (87%) were caused by enteric pathogens, including 1,459 (47%) by norovirus, 362 (12%) by Shigella, 314 (10%) by Cryptosporidium, and 155 (5%) by E. coli. Avian schistosomes were identified as the cause in 345 (11%) of the 3,125 cases. The two deaths were in persons affected by a single outbreak (two cases) caused by Naegleria fowleri. Public parks (50 [36%]) and beaches (45 [32%]) were the leading settings associated with the 140 outbreaks. Overall, the majority of outbreaks started during June-August (113 [81%]); 65 (58%) started in July. Swimmers and parents of young swimmers can take steps to minimize the risk for exposure to pathogens, toxins, and chemicals in untreated recreational water by heeding posted advisories closing the beach to swimming; not swimming in discolored, smelly, foamy, or scummy water; not swimming while sick with diarrhea; and limiting water entering the nose when swimming in warm freshwater.


Assuntos
Doenças Transmissíveis/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Água Doce , Recreação , Praias/estatística & dados numéricos , Água Doce/microbiologia , Água Doce/parasitologia , Água Doce/virologia , Humanos , Lagos/microbiologia , Lagos/parasitologia , Lagos/virologia , Parques Recreativos/estatística & dados numéricos , Lagoas/microbiologia , Lagoas/parasitologia , Lagoas/virologia , Rios/microbiologia , Rios/parasitologia , Rios/virologia , Fatores de Tempo , Estados Unidos/epidemiologia , Purificação da Água
11.
J Infect Dis ; 216(11): 1425-1433, 2017 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-28968877

RESUMO

Background: Persistent hotspots have been described after mass drug administration (MDA) for the control of schistosomiasis, but they have not been studied during the course of a multiyear MDA program. Methods: In data from a 5-year study of school-based and village-wide preventive chemotherapy strategies for Schistosoma mansoni, spatial scan statistics were used to find infection hotspots in 3 populations: 5- to 8-year-olds, 9- to 12-year-olds, and adults. Negative binomial regression was used to analyze changes from baseline, and receiver operating characteristic analyses were used to predict which villages would reach prevalence and intensity endpoints. Results: We identified a persistent hotspot, not associated with study arm, where S. mansoni infection prevalence and intensity did not decrease as much as in villages outside the hotspot. Significant differences from baseline were realized after 1 year of MDA: we did not identify factors that moderated this relationship. Villages meeting specified endpoints at year 5 were predicted from prior year data with moderately high sensitivity and specificity. Conclusions: The MDA strategies were less effective at reducing prevalence and intensity in the hotspot compared with other villages. Villages that reached year 5 endpoints could be detected earlier, which may provide the opportunity to amend intervention strategies.


Assuntos
Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Adulto , Animais , Criança , Pré-Escolar , Estudos Transversais , Mapeamento Geográfico , Humanos , Quênia , Praziquantel/administração & dosagem , Prevalência , Schistosoma mansoni/patogenicidade , Esquistossomose/tratamento farmacológico , Instituições Acadêmicas , Topografia Médica
12.
Infect Immun ; 84(5): 1371-1386, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26883596

RESUMO

Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucα3GalNAcß4(Fucα3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core ß-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis.


Assuntos
Antígenos de Helmintos/imunologia , Polissacarídeos/imunologia , Schistosoma mansoni/imunologia , Zigoto/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/química , Antígenos de Helmintos/isolamento & purificação , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Macaca mulatta , Espectrometria de Massas , Camundongos , Análise em Microsséries , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ligação Proteica
13.
BMC Infect Dis ; 16: 229, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27230666

RESUMO

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. METHODS: Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. RESULTS: These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. CONCLUSIONS: We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. TRIAL REGISTRATION: The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).


Assuntos
Anti-Helmínticos/administração & dosagem , Praziquantel/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Esquistossomose/epidemiologia , África/epidemiologia , Animais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prevalência , Serviços Preventivos de Saúde , Schistosoma haematobium , Schistosoma mansoni , Esquistossomose/prevenção & controle
14.
Clin Infect Dis ; 61 Suppl 8: S837-48, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26602621

RESUMO

Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of this infection, which affects 11% of women aged ≥40 years and a disproportionately high percentage of black women. Particularly high prevalences have been identified among sexually transmitted disease (STD) clinic patients and incarcerated individuals. This article reviews and updates scientific evidence in key topic areas used for the development of the 2015 STD Treatment Guidelines published by the Centers for Disease Control and Prevention. Current evidence is presented regarding conditions associated with Trichomonas vaginalis infection, including human immunodeficiency virus (HIV) and pregnancy complications such as preterm birth. Nucleic acid amplification tests and point-of-care tests are newly available diagnostic methods that can be conducted on a variety of specimens, potentially allowing highly sensitive testing and screening of both women and men at risk for infection. Usually, trichomoniasis can be cured with single-dose therapy of an appropriate nitroimidazole antibiotic, but women who are also infected with HIV should receive therapy for 7 days. Antimicrobial resistance is an emerging concern.


Assuntos
Antiprotozoários/uso terapêutico , Infecções Assintomáticas , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Tricomoníase/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Trichomonas vaginalis , Infecções Assintomáticas/epidemiologia , Centers for Disease Control and Prevention, U.S. , Farmacorresistência Bacteriana , Medicina Baseada em Evidências , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/microbiologia , Fatores de Risco , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/microbiologia , Vaginite por Trichomonas/epidemiologia , Vaginite por Trichomonas/microbiologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/genética , Estados Unidos/epidemiologia
15.
Lancet ; 383(9936): 2253-64, 2014 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-24698483

RESUMO

Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.


Assuntos
Esquistossomose/prevenção & controle , Esquistossomicidas/uso terapêutico , Adolescente , Adulto , Distribuição por Idade , Idoso , Animais , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/métodos , Efeitos Psicossociais da Doença , Feminino , Saúde Global , Humanos , Imunidade Celular , Lactente , Estágios do Ciclo de Vida/fisiologia , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Schistosoma/crescimento & desenvolvimento , Esquistossomose/diagnóstico , Esquistossomose/epidemiologia , Adulto Jovem
16.
Appl Environ Microbiol ; 81(12): 4207-15, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25862226

RESUMO

Cercarial dermatitis, also known as swimmer's itch, is an allergenic skin reaction followed by intense itching caused by schistosome cercariae penetrating human skin. Cercarial dermatitis outbreaks occur globally and are frequently associated with freshwater lakes and are occasionally associated with marine or estuarine waters where birds reside year-round or where migratory birds reside. In this study, a broadly reactive TaqMan assay targeting 18S rRNA gene (ribosomal DNA [rDNA]) sequences that was based on a genetically diverse panel of schistosome isolates representing 13 genera and 20 species (the 18S rDNA TaqMan assay) was developed. A PCR assay was also developed to amplify a 28S rDNA region for subsequent sequencing to identify schistosomes. When applied to surface water samples seeded with Schistosoma mansoni cercariae, the 18S rDNA TaqMan assay enabled detection at a level of 5 S. mansoni cercariae in 100 liters of lake water. The 18S rDNA TaqMan and 28S rDNA PCR sequencing assays were also applied to 100-liter water samples collected from lakes in Nebraska and Wisconsin where there were reported dermatitis outbreaks. Avian schistosome DNA was detected in 11 of 34 lake water samples using the TaqMan assay. Further 28S rDNA sequence analysis of positive samples confirmed the presence of avian schistosome DNA and provided a preliminary identification of the avian schistosomes in 10 of the 11 samples. These data indicate that the broadly schistosome-reactive TaqMan assay can be effective for rapid screening of large-volume water samples for detection of avian schistosomes, thereby facilitating timely response actions to mitigate or prevent dermatitis outbreaks. Additionally, samples positive by the 18S rDNA TaqMan assay can be further assayed using the 28S rDNA sequencing assay to both confirm the presence of schistosomes and contribute to their identification.


Assuntos
Aves/parasitologia , Água Doce/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Schistosomatidae/isolamento & purificação , Análise de Sequência de DNA/métodos , Animais , Sequência de Bases , Doenças das Aves/parasitologia , DNA Ribossômico/genética , Microbiologia Ambiental , Humanos , Limite de Detecção , Dados de Sequência Molecular , Nebraska , Filogenia , Schistosomatidae/genética , Alinhamento de Sequência , Dermatopatias Parasitárias/diagnóstico , Dermatopatias Parasitárias/prevenção & controle , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/veterinária , Wisconsin
17.
Glycobiology ; 24(7): 602-18, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24727442

RESUMO

Schistosomiasis is a debilitating parasitic disease of humans, endemic in tropical areas, for which no vaccine is available. Evidence points to glycan antigens as being important in immune responses to infection. Here we describe our studies on the comparative humoral immune responses to defined schistosome-type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and mice. Rhesus anti-glycan responses over the course of infection were screened on a defined glycan microarray comprising semi-synthetic glycopeptides terminating with schistosome-associated or control mammalian-type glycan epitopes, as well as a defined glycan microarray of mammalian-type glycans representing over 400 glycan structures. Infected rhesus monkeys generated a high immunoglobulin G (IgG) antibody response to the core xylose/core α3 fucose epitope of N-glycans, which peaked at 8-11 weeks post infection, coinciding with maximal ability to kill schistosomula in vitro. By contrast, infected humans generated low antibody levels to this epitope. At 18 months following praziquantel therapy to eliminate the parasite, antibody levels were negligible. Mice chronically infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc (GalNAcß1, 4(Fucα1, 3)GlcNAc) IgM antibodies, but lacked a robust response to the core xylose/core α3 fucose N-glycan antigens compared with other species studied, and their sera demonstrated an intermediate level of schistosomula killing in vitro. These differential responses to parasite glycan antigens may be related to the ability of rhesus monkeys to self-cure in contrast to the chronic infection seen in humans and mice. Our results validate defined glycan microarrays as a useful technology to evaluate diagnostic and vaccine antigens for schistosomiasis and perhaps other infections.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Imunoglobulina G/imunologia , Lactose/análogos & derivados , Esquistossomose mansoni/imunologia , Adulto , Animais , Epitopos , Humanos , Lactose/imunologia , Macaca mulatta , Camundongos , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Especificidade da Espécie
18.
Am J Trop Med Hyg ; 110(2): 250-253, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38190749

RESUMO

We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.


Assuntos
Doenças dos Genitais Femininos , Esquistossomose Urinária , Esquistossomose , Adulto , Feminino , Humanos , Praziquantel/uso terapêutico , Zâmbia/epidemiologia , Genitália Feminina , Esquistossomose Urinária/tratamento farmacológico
19.
Am J Trop Med Hyg ; 110(1): 90-97, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38011731

RESUMO

The first nationally representative, population-based study of schistosomiasis seroprevalence in Nigeria was conducted using blood samples and risk-factor data collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). Schistosomiasis seroprevalence was estimated by analyzing samples for reactivity to schistosome soluble egg antigen (SEA) in a multiplex bead assay; NAIIS survey data were assessed to identify potential risk factors for seropositivity. The SEA antibody data were available for 31,459 children aged 0 to 14 years. Overall seroprevalence was 17.2% (95% CI: 16.3-18.1%). Seropositive children were identified in every age group, including children < 5 years, and seroprevalence increased with increasing age (P < 0.0001). Several factors were associated with increased odds of seropositivity, including being a boy (odds ratio [OR] = 1.34, 95% CI: 1.24-1.45), living in a rural area (OR = 2.2, 95% CI: 1.9-2.5), and animal ownership (OR = 1.67, 95% CI: 1.52-1.85). Access to improved sanitation and drinking water sources were associated with decreased odds of seropositivity (OR = 0.52, 95% CI: 0.47-0.58 and OR = 0.53, 95% CI: 0.47-0.60, respectively) regardless of whether the child lived in a rural (sanitation: adjusted odds ratio [aOR] = 0.7, 95% CI: 0.6-0.8; drinking water: aOR = 0.7, 95% CI: 0.6-0.8) or urban area (sanitation: aOR = 0.6, 95% CI: 0.5-0.7; drinking water: aOR = 0.5, 95% CI: 0.4-0.6), highlighting the importance of these factors for schistosomiasis prevention and control. These results identified additional risk populations (children < 5 years) and a new risk factor (animal ownership) and could be used to monitor the impact of control programs.


Assuntos
Água Potável , Esquistossomose , Criança , Masculino , Animais , Humanos , Estudos Soroepidemiológicos , Nigéria/epidemiologia , Esquistossomose/epidemiologia , Fatores de Risco , Schistosoma
20.
Infect Immun ; 81(5): 1411-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23429535

RESUMO

Trichomonas vaginalis is an extracellular protozoan parasite that binds to the epithelium of the human urogenital tract during infection. In this study, we examined the propensities of 26 T. vaginalis strains to bind to and lyse prostate (BPH-1) and ectocervical (Ect1) epithelium and to lyse red blood cells (RBCs). We found that only three of the strains had a statistically significant preference for either BPH-1 (MSA1103) or Ect1 (LA1 and MSA1123). Overall, we observed that levels of adherence are highly variable among strains, with a 12-fold range of adherence on Ect1 cells and a 45-fold range on BPH-1 cells. Cytolysis levels displayed even greater variability, from no detectable cytolysis to 80% or 90% cytolysis of Ect1 and BPH-1, respectively. Levels of adherence and cytolysis correlate for weakly adherent/cytolytic strains, and a threshold of attachment was found to be necessary to trigger cytolysis; however, this threshold can be reached without inducing cytolysis. Furthermore, cytolysis was completely blocked when we prevented attachment of the parasites to host cells while allowing soluble factors complete access. We demonstrate that hemolysis was a rare trait, with only 4 of the 26 strains capable of lysing >20% RBCs with a 1:30 parasite/RBC ratio. Hemolysis also did not correlate with adherence to or cytolysis of either male (BPH-1)- or female (Ect1)-derived epithelial cell lines. Our results reveal that despite a broad range of pathogenic properties among different T. vaginalis strains, all strains show strict contact-dependent cytolysis.


Assuntos
Células Epiteliais/parasitologia , Trichomonas vaginalis/fisiologia , Adesão Celular/fisiologia , Linhagem Celular , Células Epiteliais/citologia , Feminino , Hemólise/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Próstata/parasitologia , Vagina/parasitologia
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