RESUMO
Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.
RESUMO
Schistosoma japonicum is endemic in the Philippines. The Kato-Katz (KK) method was used to diagnose S. japonicum. This is impractical, particularly when the sample size is limited. Knowledge on point-of-care circulating cathodic antigen (CCA) test performance for S. japonicum is limited. Determining the sensitivity and specificity of new diagnostics is difficult when the gold standard test is less effective or absent. Latent class analysis (LCA) can address some limitations. A total of 484 children and 572 adults from the Philippines were screened for S. japonicum. We performed Bayesian LCA to estimate the infection prevalence, sensitivity and specificity of each test by stratifying them into two age groups. Observed prevalence assessed by KK was 50.2% and 31.8%, and by CCA was 89.9% and 66.8%, respectively. Using Bayesian LCA, among children, the sensitivity and specificity of CCA were 94.8% (88.7-99.4) and 21.5% (10.5-36.1) while those of KK were 66.0% (54.2-83.3) and 78.1% (61.1-91.3). Among adults, the sensitivity and specificity of CCA were 86.4% (76.6-96.9) and 62.8% (49.1-81.1) while those of KK were 43.6% (35.1-53.9) and 85.5% (75.8-94.6). Overall, CCA was more sensitive than KK, regardless of the age group at diagnosis, as KK was more specific. KK and CCA have different diagnostic performance, which should inform their use in the planning and implementation of S. japonicum control programs.
Assuntos
Schistosoma japonicum , Esquistossomose mansoni , Criança , Adulto , Animais , Humanos , Schistosoma mansoni , Antígenos de Helmintos , Teorema de Bayes , Análise de Classes Latentes , Sistemas Automatizados de Assistência Junto ao Leito , Fezes/química , Sensibilidade e Especificidade , PrevalênciaRESUMO
In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.
Assuntos
Vírus da Dengue , Dengue , Infecções por Flavivirus , Flavivirus , Infecção por Zika virus , Zika virus , Animais , Flavivirus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Zika virus/genética , Vírus da Dengue/genética , Estudos Soroepidemiológicos , Anticorpos Antivirais , Infecções por Flavivirus/diagnóstico , Infecções por Flavivirus/epidemiologia , Vírus da Febre Amarela , Reações CruzadasRESUMO
In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.
RESUMO
Introduction: Dengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9-45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016-2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections. Methods: We evaluated the performance of a candidate assay, the DENV1-4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines. Results: The sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher's exact test), demonstrating the feasibility of the assay and algorithms in clinical practice. Conclusion: The UH DENV1-4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.
Assuntos
Vírus da Dengue , Dengue , Criança , Animais , Humanos , Dengue/diagnóstico , Dengue/epidemiologia , Filipinas/epidemiologia , Anticorpos Antivirais , Imunoglobulina GRESUMO
Objectives: Fetal alcohol spectrum disorder (FASD) captures the broad range of emotional, cognitive, behavioral, and congenital abnormalities associated with maternal alcohol consumption, and women living in resource-limited settings may be higher risk. This study aims to examine knowledge, attitudes, practices, and beliefs (KAPB) of women in Leyte, The Philippines regarding prenatal alcohol consumption. Methods: One hundred postpartum women were recruited from a birth cohort in Leyte. A prenatal alcohol use KAPB survey was constructed in Waray, the local language. The survey was administered in June-September 2019. Descriptive statistics, chi-squared test, and Fisher's exact test were used to analyze responses. Results: Seventy-five percent of subjects reported drinking tuba, a local palm wine, during pregnancy. Most participants (75%) did not believe tuba contained alcohol. Women who believed tuba contains no alcohol were more likely to drink tuba during pregnancy (81.3%) than women who believed tuba contains alcohol (56.0%), X2(1, N = 100) = 6.41, p = .011. Women who drank tuba during pregnancy were more likely to believe tuba has health benefits (60%) than women who did not drink tuba during pregnancy (12%), Fisher's exact p < .05, citing increased red blood cell count and unproven antiparasitic qualities. Fifteen percent of subjects reported having fed their babies tuba. Nearly all (98%) were willing to attenuate tuba/alcohol consumption if told that this practice negatively impacts pregnancies. Conclusion: Misinformation about tuba appears widespread in Leyte. Educating women of reproductive age in Leyte regarding prenatal tuba use may lead to a reduction in tuba use.
RESUMO
BACKGROUND: We compared individuals' self-reported water contact from a questionnaire to direct observation of water contact. Questionnaires that accurately capture water contact are necessary to risk-stratify individuals and communities at high risk for schistosomiasis. METHODS: Individuals (N=677) ages 7-30 y were included from three Schistosoma japonicum-endemic villages in Leyte, The Philippines. Each individual was observed for 12 d over the course of the 18-month study and the questionnaire was administered six times. A questionnaire index was derived that captured the number of self-reported contacts with water bodies for any purpose. An exposure index was created based on the sum of contacts that was weighted by the percentage of body surface area (BSA) exposed and exposure duration. RESULTS: Of 16 water contact activities, only bathing and washing clothes exhibited a significant, positive correlation between self-reported contacts and the observed exposure index related to those contacts. CONCLUSIONS: We found that only the reported frequencies of bathing and washing clothes were significantly related to an individual's overall observed exposure index, while use of all reported contacts was not related to the observed exposure. This study further supports the need for questionnaires to be augmented by some measure of how much BSA is exposed and/or time is spent in the water on average for a specific activity.
Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Adolescente , Adulto , Animais , Criança , Humanos , Filipinas/epidemiologia , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/prevenção & controle , Autorrelato , Água , Adulto JovemRESUMO
In the past decade, ecological surveys emphasized rats and dogs as the most significant animal reservoirs for Schistosoma japonicum (S.j) in the Philippines. However, recent studies demonstrated 51-91% prevalence of schistosomiasis among water buffalo using qPCR in the Sj endemic regions in the Philippines. In order to resolve the inconsistency of reported surveys regarding Sj endemicity among carabao, a domestic water buffalo that is the most important draught animal, we introduced 42 schistosome negative water buffalo to Macanip, Jaro municipality, Leyte, the Philippines, a subsistence rice-farming village that has been the focus of schistosomiasis japonica studies of our group for the past 20 years. We conducted perfusion to the remaining 34 buffalo that survived 10 months of nature exposure and Typhoon Haiyan. Thirty-three water buffalo were found to be positive with at least 1 pair of worms from the mesenteric vein. The infection rate is 97%, with the worm burden of 94 (95% confidence interval, 49-138 worms) worms. To our knowledge, this is the first report about S. japonicum worm burden in naturally infected water buffalo in the Philippines. The fact that with less than one-year of exposure, in this human schistosomiasis endemic area, only 1 out of 34 water buffalo was uninfected is striking. Urgent attention is needed for a cost-effective technique for monitoring Sj infection in animals and humans. Meanwhile, intervention implementation, including water buffalo treatment and vaccination, should be taken into consideration.
Assuntos
Búfalos , Perfusão/efeitos adversos , Schistosoma japonicum , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/veterinária , Animais , Bovinos , Doenças dos Bovinos , Fezes/parasitologia , Humanos , Filipinas/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo RealRESUMO
In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.
Assuntos
Citocinas/metabolismo , Imunidade Materno-Adquirida , Praziquantel/administração & dosagem , Complicações Parasitárias na Gravidez/tratamento farmacológico , Esquistossomose Japônica/tratamento farmacológico , Animais , Antiprotozoários/administração & dosagem , Criança , Estudos de Coortes , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Modelos Lineares , Masculino , Análise Multivariada , Filipinas , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Schistosoma japonicum/efeitos dos fármacos , Esquistossomose Japônica/imunologia , Resultado do TratamentoRESUMO
The World Health Organization Western Pacific Region (WPR) set a hepatitis B virus (HBV) control target to achieve HBV surface antigen (HBsAg) prevalence of <1% among children aged 5 years by 2017. The estimated HBsAg prevalence in the Philippines among adults was 16.7% during the pre-vaccine era. We estimated the HBsAg seroprevalence among children aged 5-7 years to measure the impact of vaccination. We conducted a household serosurvey, using a three-stage cluster survey methodology (provinces, clusters, and households). We estimated HBsAg prevalence using a rapid, point-of-care HBsAg test and calculated vaccination coverage by reviewing vaccination records or by caregiver recall. A questionnaire was administered to assess demographic variables for the child and family. We assessed the association between chronic HBV infection, vaccination coverage, and demographic variables, accounting for the complex survey design. Of the 2178 children tested, HBsAg was detected in 15 children [0.8%, 95% confidence interval (CI): 0.4, 1.7]. Only two of the HBsAg-positive children had been fully vaccinated against HBV. Based on documented vaccination or caregiver recall for the survey population, hepatitis B vaccine birth dose (HepB-BD) coverage was 53%, and the third dose hepatitis B vaccination (HepB3) coverage was 73 percent. Among the 1362 children with documented HepB-BD, timely HepB-BD coverage (given within 24 h of birth) was 43%; children born outside a health facility were less likely to receive a timely HepB-BD than those born in a health facility (adjusted odds ratio 0.10, 95% CI: 0.04, 0.23). HBsAg prevalence among children in the Philippines has decreased compared to the prevalence among adults in the pre-vaccination era. Strategies to further reduce HBsAg prevalence include ensuring that all children, whether born in health facilities or at home, receive a timely HepB-BD, and increasing HepB-BD and HepB3 coverage to reach the WPR goals of ≥95% coverage.
Assuntos
Vacinas contra Hepatite B , Hepatite B , Adulto , Criança , Pré-Escolar , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B , Humanos , Filipinas/epidemiologia , Estudos Soroepidemiológicos , VacinaçãoRESUMO
Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum-endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (Nâ =â 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.
Assuntos
Anticorpos Anti-Helmínticos , Schistosoma japonicum , Esquistossomose Japônica , Vacinas , Animais , Anticorpos Anti-Helmínticos/imunologia , Resistência à Doença , Humanos , Recidiva Local de Neoplasia , Praziquantel/uso terapêutico , Proteoma , Reinfecção/prevenção & controle , Schistosoma japonicum/genética , Esquistossomose Japônica/prevenção & controleRESUMO
Schistosomiasis is a chronic but preventable disease that affects 260 million people worldwide. In the Philippines, 860,000 people are afflicted with Schistosoma japonicum annually, and another 6.7 million live in endemic areas. The disease's complex epidemiology as well as the influence of poverty in endemic areas demand an integrated, multi-sectoral approach to disease control. Results from behavioral or sociocultural studies on schistosomiasis could improve the content and impact of schistosomiasis control in rural villages in the Philippines. We investigated knowledge, attitudes and practices related to schistosomiasis transmission and control in an endemic village in Leyte Province, Philippines. We administered a questionnaire to 219 participants covering 1) knowledge and attitudes related to schistosomiasis, its symptoms, and its transmission; 2) attitudes and practices in relation to schistosomiasis prevention; 3) willingness to comply with public health control programs; and 4) whether the respondent had previously contracted schistosomiasis. Responses revealed fairly high measures of schistosomiasis knowledge (mean 17.0 out of 23 questions, range 6-23), but also inconsistent disease prevention behavior. A high proportion of participants (72.6%, n = 159) reported previous disease. Participant belief in the preventability of schistosomiasis was revealed to be a key attitude, as carabao owners who believed in prevention were over five times more likely to be willing to vaccinate their carabaos (OR = 5.24, 95% CI 1.20-27.68, P = 0.04). Additionally, participants who did not believe in prevention were about twice as likely to report previous disease (OR = 2.31, 95% CI 1.02-5.63, P = 0.05). Our results suggest that future public health interventions should address barriers to disease-preventing behavior, as well as maintaining community belief in disease prevention. Comprehensive disease control programs should be supplemented by sociocultural and behavioral context in order to improve their impact in endemic communities.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Esquistossomose/psicologia , Esquistossomose/transmissão , Adulto , Idoso , Animais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas/epidemiologia , População Rural/estatística & dados numéricos , Schistosoma japonicum/fisiologia , Esquistossomose/parasitologia , Esquistossomose/prevenção & controle , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Schistosomiasis japonica is a zoonosis and presents significant public health problems in China and the Philippines. Vaccines targeting domestic animals constitute attractive control measures. METHODS: We conducted three vaccine trials to evaluate the protective efficacy of recombinant full-length paramyosin (rSj97) in water buffalo. Animals were immunized with 3 doses of rSj97 adjuvanted with ISA206 at 250µg/dose or 500µg/dose at 4wk intervals before challenge with 1000 Schistosoma japonicum cercariae. The primary outcome was worm burden assessed by portal perfusion 8-10weeks post challenge. Safety measures included weight, temperature, body condition score, hemogram and routine assays for hepatic and renal function. RESULTS: The three-dose regimen was well tolerated in all three trials. In the first trial, vaccinated buffalo had 51.5% lower worm burden post challenge compared to controls. In the second trial, buffalo immunized with 500µg/dose of rSj97 had 57.8% lower worm burden compared to controls (p=0.026). A similar but not significant reduction (60.9%) was observed with animals administered with 250ug rSj97/dose. In the third trial, buffalo immunized with a 500µg/dose of rSj97 had 57.8% lower worm burden compared to controls (p=0.014). CONCLUSIONS: These findings indicated that rSj97 is a safe and promising vaccine candidate for schistosomiasis japonica in water buffalo.
Assuntos
Búfalos , Doenças dos Bovinos/prevenção & controle , Proteínas de Helminto/administração & dosagem , Esquistossomose Japônica/veterinária , Tropomiosina/administração & dosagem , Vacinas/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Feminino , Proteínas de Helminto/imunologia , Masculino , Carga Parasitária , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Esquistossomose Japônica/prevenção & controle , Tropomiosina/imunologia , Vacinação/veterináriaRESUMO
Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies. We conclude with a proposed developmental plan to move Pmy toward Phase I clinical trials.
RESUMO
The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis) have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD) technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle) from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively) and carabao (80.00% and 55.24%, respectively). The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively). The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines.
Assuntos
Doenças dos Bovinos/epidemiologia , Fasciola/isolamento & purificação , Fasciolíase/veterinária , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/veterinária , Zoonoses/epidemiologia , Animais , Búfalos/parasitologia , Bovinos , Doenças dos Bovinos/transmissão , China/epidemiologia , Fasciolíase/epidemiologia , Fasciolíase/transmissão , Fezes/parasitologia , Humanos , Filipinas/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/transmissão , Zoonoses/parasitologia , Zoonoses/transmissãoRESUMO
BACKGROUND: Schistosomes infect 200 million individuals annually and cause significant hepatic fibrosis in up to 20%. Little is known regarding the mechanisms of schistosome-associated hepatic fibrosis in humans, and few biomarkers for risk of fibrosis have been identified. METHODS: We treated 611 Schistosoma japonicum-infected Filipinos with praziquantel (PZQ) and performed ultrasound to quantify hepatic fibrosis at baseline and 12 months after PZQ treatment. We developed a multiplexed assay (FibroPlex) that quantifies predictors and effect modifiers of fibrosis. We measured FibroPlex analytes produced by peripheral blood mononuclear cells stimulated with schistosome egg antigen 4 weeks after PZQ treatment and related these levels to risk of fibrosis 1 year after PZQ treatment. RESULTS: After adjusting for potential confounders, including baseline grade of fibrosis, individuals with detectable tissue inhibitor of matrix-metalloprotease-1 (TIMP-1) had a 3.5-fold greater risk of fibrosis 1 year after PZQ treatment, compared with individuals with undetectable levels (odds ratio, 3.48; 95% confidence interval, 1.41-8.43; P = .007). DISCUSSION: Because TIMP-1 inhibits most matrix metalloproteases, which are responsible for collagen degradation, these data suggest that schistosome-associated hepatic fibrosis results, in part, from excessive inhibition of collagen remodeling. These data further suggest that TIMP-1 is a promising biomarker for assessing risk of hepatic fibrosis in schistosomiasis and, potentially, other infectious and noninfectious causes of liver disease.
Assuntos
Cirrose Hepática/sangue , Cirrose Hepática/parasitologia , Esquistossomose Japônica/sangue , Esquistossomose Japônica/complicações , Inibidor Tecidual de Metaloproteinase-1/sangue , Adolescente , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Biomarcadores/sangue , Criança , Estudos de Coortes , Colágeno/metabolismo , Fezes/parasitologia , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Masculino , Filipinas , Praziquantel/uso terapêutico , Prognóstico , Análise de Regressão , Fatores de Risco , Schistosoma japonicum , Esquistossomose Japônica/diagnóstico por imagem , Esquistossomose Japônica/tratamento farmacológico , Ultrassonografia , Adulto JovemRESUMO
One small previous study found that praziquantel reduced hookworm infection. In this study, 607 subjects were enrolled in a longitudinal study. At enrollment and every 3 months for 18 months, three stool samples were collected, and the intensity of infection with Schistosoma japonicum and soil-transmitted helminths (STHs) was quantified. All subjects were treated with 60 mg/kg praziquantel at baseline. Three months post-treatment, the percent of subjects who were hookworm-infected decreased to 46.5% from 61% at baseline. The putative cure rate was 23.7%. The 95% confidence interval around the change in hookworm egg counts from baseline to 6 and 12 months post-treatment was negative and did not include zero. The percent reduction in hookworm egg counts from baseline to 3 months post-treatment was 40.8%. Praziquantel treatment did not decrease the infection intensity of STHs. Control programs using praziquantel may have the added benefit of reducing hookworm infection and anemia in areas of coendemnicity.
Assuntos
Anti-Helmínticos/uso terapêutico , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/epidemiologia , Praziquantel/uso terapêutico , Adolescente , Adulto , Animais , Criança , Fezes/parasitologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Contagem de Ovos de Parasitas , Papagaios , Filipinas/epidemiologia , Schistosoma japonicum , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/epidemiologia , Adulto JovemRESUMO
Cysticercosis is a significant public health problem in countries where pigs are raised for consumption and remains an important cause of neurological disease worldwide. The Philippines is considered an endemic area for cysticercosis because cases in both humans and pigs have been reported; however, epidemiologic information stays limited. We conducted a pilot survey of the seroprevalence of human cysticercosis in a village in Leyte, the Philippines, by measuring antibody specific for Taenia solium cyst-fluid antigen. There were 497 subjects aged 7-30 years in our study and most subjects were infected with one or more helminths. The overall cysticercosis seroprevalence in this population was 24.6% (95% CI: 20.82% ~ 28.58%) with no significant difference based on age, sex, or other helminth coinfection status. Although the sample may not be representative of the whole community, the findings suggest that cysticercosis is a significant, but underrecognized public health concern in the Philippines.
RESUMO
BACKGROUND: Many studies have addressed the relationship between iron deficiency anemia (IDA) and cognitive impairment, but none have evaluated the role of non-iron deficiency anemia (NIDA). One of the main causes of NIDA in developing countries is AI, largely due to infectious diseases, whereby iron is shunted away from bio-available forms to storage forms, making it less accessible for use by host tissues. The objective of this study was to determine the effect of NIDA, due largely to AI in this context, on cognitive function after adjustment for potential confounders. METHODOLOGY: This cross-sectional study was conducted in Leyte, The Philippines among 322 children ages 7-18 years. Blood samples were collected and analyzed at the time of cognition testing. Three stool samples were collected and evaluated by the Kato Katz method for quantitative assessment for Schistosoma japonicum and geo-helminth infection. Socio-economic status (SES) was evaluated by survey. Linear regression models were used to quantify the adjusted relationship between performance in different cognitive domains and both IDA and NIDA. PRINCIPAL FINDINGS: After adjusting for age, sex, SES and nutritional status, children in the NIDA had lower scores on the PNIT (P = <0.05) and the WRAML memory domain (P<0.05) compared to children in the non-anemic group. Children in the IDA had lower performance on the PNIT compared to the non-anemic group after controlling for potential confounders (P<0.05). CONCLUSIONS: NIDA, predominantly due to AI in this context, was related to lower performance on two tests of cognitive function. This is likely due to decreased delivery of iron to host tissues in this context, including the CNS.
Assuntos
Anemia/psicologia , Cognição , Adolescente , Anemia/imunologia , Anemia/metabolismo , Criança , Estudos Transversais , Feminino , Humanos , Ferro/metabolismo , Masculino , Estado Nutricional , Filipinas , Classe SocialRESUMO
Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatment-based control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n = 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P = 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n = 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n = 274), even after adjusting for potential confounders (P = 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.