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Purpose of Review: Giardia lamblia is a common intestinal parasite worldwide, mainly in children from low- and middle-income countries (LMIC). Also, it has been associated with increased intestinal permeability, stunting, and cognitive impairment. Nonetheless, the pathogenesis of long-term consequences is difficult to elucidate. Recent Findings: Recent studies try to understand the long-term consequences of Giardia infections. First, well-characterized studies associate Giardia with intestinal damage and child growth. Second, infections appear not to be associated with inflammation, but "lack of inflammation" may not, however, entirely exclude a pro-inflammatory pathway. Finally, some important amino acids are lower and could contribute to prolongate stunting and cognitive deficit. Summary: Giardia infections in LMIC used to be associated with child growth shortfalls, gut permeability, and cognitive deficits. Multifactorial effects could be associated with Giardia, including nutritional, altered microbiota, and generation of potentially toxic microbial metabolic byproducts, all together increasing risk of long-term outcomes.
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Histone post-translational modifications are extensively studied for their role in regulating gene transcription and cellular environmental adaptation. Research into these modifications has recently begun in the protozoan parasite Giardia lamblia, focusing on histone-modifying enzymes and specific post-translational changes. In the transformation from the trophozoite to the cyst form in the life cycle of this parasite, significant morphological and genetic alterations occur, culminating in the synthesis of cyst wall proteins responsible for forming the protective cyst wall. It has been previously demonstrated that histone deacetylation is required during encystation and that the enzyme lysine methyltransferase 1 is involved in the upregulation of encystation. Our study aims to extend the analysis to lysine methyltransferase 2 (GlKMT2) function. For this, two constructs were generated: one that downregulate the expression of GLKMT2 via antisense (glkmt2-as transgenic cells) and the other overexpressing GlKMT2 (glkmt2-ha transgenic cells). We found that the glktm2-as transgenic cells showed an arrest in progress at the late encystation stage. Consequently, the number of cysts produced was lower than that of the control cells. On the other hand, we found that the overexpression of GlKMT2 acts as a negative mutant of the enzyme. In this way, these glktm2-ha transgenic cells showed the same behavior during growth and encystation as glkmt2-as transgenic cells. This interplay between different enzymes acting during encystation reveals the complex process behind the differentiation of the parasite. Understanding how these enzymes play their role during the encystation of the parasite would allow the design of inhibitors to control the parasite.
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Giardia lamblia , Encistamento de Parasitas , Proteínas de Protozoários , Giardia lamblia/enzimologia , Giardia lamblia/genética , Giardia lamblia/crescimento & desenvolvimento , Giardia lamblia/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Encistamento de Parasitas/fisiologia , Encistamento de Parasitas/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Processamento de Proteína Pós-TraducionalRESUMO
Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.
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Antiprotozoários , Giardia lamblia , Giardíase , Simulação de Acoplamento Molecular , United States Food and Drug Administration , Giardíase/tratamento farmacológico , Giardia lamblia/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/química , Estados Unidos , Humanos , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/antagonistas & inibidores , Simulação de Dinâmica MolecularRESUMO
Giardiasis is the most common intestinal parasitic disease worldwide. Clinical presentation ranges from asymptomatic to abdominal pain, diarrhea, and iron deficiency anemia. Treatment modalities include tinidazole, metronidazole, and paromomycin. We present a case of an adult man with anemia and suspected gastrointestinal bleeding who was found to have a duodenal nodule consistent with Brunner gland hyperplasia, and biopsy also showed Giardia. Limited case reports of Giardia diagnosed by duodenal biopsy are found in the literature. To the best of our knowledge, this is the first report of giardiasis presenting as Brunner gland hyperplasia.
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Las infecciones parasitarias intestinales son comunes a nivel mundial, especialmente en naciones en desarrollo, y conllevan una significativa carga de morbilidad. Objetivo. Estimar la prevalencia de parasitismo intestinal en los niños y niñas en edad escolar de 6 a 12 años que residen en el centro poblado Jancao (Huánuco) Perú. Materiales y métodos. Se desarrolló mediante un estudio observacional de cohorte transversal. Se calculó una muestra con un nivel de confianza del 95%, un error estimado del 5% y una proporción esperada de enfermos de 0.2. La muestra calculada fue de 186 personas. Los criterios de inclusión considerados fueron varon o hembra, de 6 a 12 años. Resultados. Fueron positivos 27% de los indviduos muestreados. La Giardía lambia y la Tenia solium tuvieron los mayores porcentajes de prevalencia en la población estudiada 24% y 18% respectivamente, ambos porcentajes difieren significativamente con los de Entoameba histolytica y Enterobius vermicularis para p<2.2e-16. La distribución por sexos de la prevalencia de las parasitosis identíficadas no mostró diferencias significativas en ninguna de las variantes analizadas. La distribución de parasitosis intestinales según tres estratos etareos de forma general no generó diferencias significativas entre los valores observados. Conclusiones. La parasitosis de mayor prevalencia en niños entre las edades comprendidas de 6 a 7 años, 8 a 9 años, 10 a 12 años en el centro poblado Jancao de Huánuco en Perú corresponden a Giardia lambia y Tenia solium.
Intestinal parasitic infections are common worldwide, especially in developing nations, and carry a significant burden of disease. Objective. To estimate the prevalence of intestinal parasitism in school-aged children aged 6 to 12 years residing in the Jancao population center (Huánuco) Peru. Materials and methods. It was developed by means of a cross-sectional observational cohort study. A sample was calculated with a confidence level of 95%, an estimated error of 5% and an expected proportion of patients of 0.2. The calculated sample was 186 persons. The inclusion criteria considered were male or female, aged 6 to 12 years. Results. Twenty-seven percent of the sampled individuals were positive. Giardia lambia and Taenia solium had the highest prevalence percentages in the studied population 24% and 18% respectively, both percentages differed significantly with those of Entoameba histolytica and Enterobius vermicularis for p<2.2e-16. The distribution by sex of the prevalence of identeric parasitosis did not show significant differences in any of the variants analyzed. The distribution of intestinal parasitosis according to three age strata in general did not generate significant differences between the values observed. Conclusions. The most prevalent parasitosis in children between the ages of 6 to 7 years, 8 to 9 years, 10 to 12 years in the Jancao de Huánuco population center in Peru corresponds to Giardia lambia and Taenia solium.
As infecções parasitárias intestinais são comuns em todo o mundo, especialmente nos países em desenvolvimento, e representam uma carga significativa de doenças. Objetivo. Estimar a prevalência de parasitismo intestinal em crianças em idade escolar, com idades entre 6 e 12 anos, residentes no centro da aldeia de Jancao (Huánuco), Peru. Materiais e métodos. Este foi um estudo de coorte observacional transversal. Foi calculada uma amostra com um nível de confiança de 95%, um erro estimado de 5% e uma proporção esperada de doentes de 0,2. A amostra calculada foi de 186 pessoas. Os critérios de inclusão considerados foram: sexo masculino ou feminino, com idades compreendidas entre os 6 e os 12 anos. Resultados. Vinte e sete por cento dos indivíduos da amostra foram positivos. Giardia lambia e Taenia solium apresentaram as taxas de prevalência mais elevadas na população estudada, 24% e 18%, respetivamente, diferindo significativamente das taxas de Entoameba histolytica e Enterobius vermicularis, com p<2,2e-16. A distribuição por sexo da prevalência de parasitoses identéricas não apresentou diferenças significativas em nenhuma das variantes analisadas. A distribuição das parasitoses intestinais segundo os três estratos etários, em geral, não gerou diferenças significativas entre os valores observados. Conclusões. As parasitoses mais prevalentes em crianças de 6 a 7 anos, 8 a 9 anos e 10 a 12 anos no centro populacional de Jancao de Huánuco, no Peru, correspondem a Giardia lambia e Taenia solium.
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Humanos , Masculino , Feminino , CriançaRESUMO
INTRODUCTION: The multifactorial etiology of gastroenteritis emphasizes the need for different laboratory methods to identify or exclude infectious agents and evaluate the severity of diarrheal disease. OBJECTIVE: To diagnose the infectious etiology in diarrheic children and to evaluate some fecal markers associated with intestinal integrity. MATERIALS AND METHODS: The study group comprised 45 children with diarrheal disease, tested for enteropathogens and malabsorption markers, and 76 children whose feces were used for fat evaluation by the traditional and acid steatocrit tests. RESULTS: We observed acute diarrhea in 80% of the children and persistent diarrhea in 20%. Of the diarrheic individuals analyzed, 40% were positive for enteropathogens, with rotavirus (13.3%) and Giardia duodenalis (11.1%) the most frequently diagnosed. Among the infected patients, occult blood was more evident in those carrying pathogenic bacteria (40%) and enteroviruses (40%), while steatorrhea was observed in infections by the protozoa G. duodenalis (35.7%). Children with diarrhea excreted significantly more lipids in feces than non-diarrheic children, as determined by the traditional (p<0.0003) and acid steatocrit (p<0.0001) methods. Moreover, the acid steatocrit method detected 16.7% more fecal fat than the traditional method. CONCLUSIONS: Childhood diarrhea can lead to increasingly severe nutrient deficiencies. Steatorrhea is the hallmark of malabsorption, and a stool test, such as the acid steatocrit, can be routinely used as a laboratory tool for the semi-quantitative evaluation of fat malabsorption in diarrheic children.
Introducción. La etiología multifactorial de la gastroenteritis enfatiza la necesidad de usar diferentes métodos de laboratorio para identificar o excluir agentes infecciosos y evaluar la gravedad de la enfermedad diarreica. Objetivo. Diagnosticar la etiología infecciosa de la diarrea en niños y evaluar algunos marcadores fecales asociados con la integridad intestinal. Materiales y métodos. Se estudiaron 45 niños con enfermedad diarreica, en los cuales se evaluaron la presencia de enteropatógenos y los marcadores de malabsorción. Se analizaron las muestras fecales de 76 niños, mediante las pruebas de esteatocrito tradicional y esteatocrito ácido, para la cuantificación de la grasa. Resultados. Se observó diarrea aguda en el 80 % de los niños y diarrea persistente en el 20 %. De los individuos con diarrea, el 40 % fue positivo para enteropatógenos; los más diagnosticados fueron rotavirus (13,3 %) y Giardia duodenalis (11,1 %). Entre los pacientes infectados, la sangre oculta fue más evidente en aquellos portadores de bacterias patógenas (40 %) o enterovirus (40%), mientras que la esteatorrea se observó en infecciones por el protozoo G. duodenalis (35,7 %). Los niños con diarrea excretaron significativamente más lípidos en las heces que aquellos sin diarrea, según lo determinado por los métodos de esteatocrito tradicional (p<0,0003) y esteatocrito ácido (p<0,0001). Conclusiones. La diarrea infantil puede provocar deficiencias graves de nutrientes. La esteatorrea es distintiva de la malabsorción intestinal y puede detectarse mediante la estimación del esteatocrito ácido. Esta prueba podría utilizarse de forma rutinaria como una herramienta de laboratorio para la evaluación semicuantitativa de la malabsorción de grasas en niños con diarrea.
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Diarreia , Fezes , Síndromes de Malabsorção , Humanos , Diarreia/parasitologia , Diarreia/etiologia , Diarreia/microbiologia , Fezes/parasitologia , Pré-Escolar , Lactente , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/etiologia , Masculino , Feminino , Criança , Giardíase/complicações , Esteatorreia/etiologia , Gastroenterite/complicações , Gastroenterite/parasitologia , Gastroenterite/microbiologia , Sangue OcultoRESUMO
In this study, the Quantitative Microbial Risk Assessment (QMRA) methodology was applied to estimate the annual risk of Giardia and Cryptosporidium infection associated with a water treatment plant in southern Brazil. The efficiency of the treatment plant in removing protozoa and the effectiveness of the Brazilian legislation on microbiological protection were evaluated, emphasizing the relevance of implementing the QMRA in this context. Two distinct approaches were employed to estimate the mechanical removal of protozoa: The definitions provided by the United States Environmental Protection Agency (USEPA), and the model proposed by Neminski and Ongerth. Although the raw water collected had a higher concentration of Giardia cysts than Cryptosporidium oocysts, the estimated values for the annual risk of infection were significantly higher for Cryptosporidium than for Giardia. From a general perspective, the risk values of protozoa infection were either below or very near the limit set by the World Health Organization (WHO). In contrast, all the risk values of Cryptosporidium infection exceeded the threshold established by the USEPA. Ultimately, it was concluded that the implementation of the QMRA methodology should be considered by the Brazilian authorities, as the requirements and guidelines provided by the Brazilian legislation proved to be insufficient to guarantee the microbiological safety of drinking water. In this context, the QMRA application can effectively contribute to the prevention and investigation of outbreaks of waterborne disease.
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Criptosporidiose , Cryptosporidium , Estados Unidos , Humanos , Criptosporidiose/epidemiologia , Brasil/epidemiologia , Monitoramento Ambiental , Giardia , Medição de RiscoRESUMO
Giardiasis is a parasitosis caused by Giardia lamblia with significant epidemiological and clinical importance due to its high prevalence and pathogenicity. The lack of optimal therapies for treating this parasite makes the development of new effective chemical entities an urgent need. In the search for new inhibitors of the adenylyl cyclase gNC1 obtained from G. lamblia, 14 extracts from Argentinian native plants were screened. Lepechinia floribunda and L. meyenii extracts exhibited the highest gNC1 inhibitory activity, with IC50 values of 9 and 31 µg/mL, respectively. In silico studies showed rosmarinic acid, a hydroxycinnamic acid present in both mentioned species, to be a promising anti-gNC1 compound. This result was confirmed experimentally, with rosmarinic acid showing an IC50 value of 10.1 µM. Theoretical and experimental findings elucidate the molecular-level mechanism of rosmarinic acid, pinpointing the key interactions stabilizing the compound-enzyme complex and the binding site. These results strongly support that rosmarinic acid is a promising scaffold for developing novel compounds with inhibitory activity against gNC1, which could serve as potential therapeutic agents to treat giardiasis.
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Giardiasis, caused by the protozoan Giardia intestinalis, affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health, especially in children. Prolonged giardiasis in childhood can lead to intellectual deficits and other complications. A variety of diagnostic tools, including microscopic, immunological, and molecular methods, are available for detecting G. intestinalis infection. Choosing the most suitable method can be challenging due to the abundance of options. This systematic review assesses the reliability and applicability of these diagnostic modalities. Utilizing the Dimensions and Wordart platforms for data analysis, we focus on relevant literature addressing diagnostic methods for human giardiasis. Microscopic techniques, particularly Ritchie's method, emerge as the primary choice, followed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). PCR's limited use is attributed to its high cost and infrastructure challenges in developing nations. In conclusion, our analysis supports microscopic methods as the gold standard for giardiasis diagnosis. However, in cases where symptoms persist despite a negative diagnosis, employing more sensitive diagnostic approaches is advisable.
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BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.