Invest Clin 60(1): 53 - 78, 2019 https://doi.org/10.22209/IC.v60n1a06 Blastocystosis: Epidemiological, clinical, pathogenic, diagnostic, and therapeutic aspects. José Ramón Vielma Decanato de Ingeniería de Producción Animal, Universidad Rafael Urdaneta (URU). Maracaibo, Venezuela. Laboratorio de Análisis Químico (LAQUNESUR), Universidad Nacional Experimental Sur del Lago “Jesús María Semprum” (UNESUR). Santa Bárbara de Zulia, Venezuela. Laboratorio Clínico del Hospital del Instituto Venezolano de los Seguros Sociales (IVSS) “Dr. Adolfo Pons”. Maracaibo, Venezuela. Key words: Blastocystis spp.; genotypes; epidemiology; irritable bowel syndrome; urticaria; metronidazole. Abstract. Blastocystis is a nonmoving pleomorphic stramenopile or chromist. Nineteen subtypes of this organism have been identified. It has a worldwide distribu- tion. The prevalence rates in humans are lower than 1% in developed countries and up to 100% in developing countries. It is possible to recognize the fecal-oral transmission, through ingestion of contaminated food and water, and zoonotic spreads. The diagnosis is carried out by direct fecal examination, culture and molecular techniques. Blastocystis has virulence factors such as cysteine proteases, serine proteases and legumains, mostly secreted to the pathogen-host interface. This stramenopile has been linked to gastroin- testinal symptoms, irritable bowel syndrome, urticarial and arthritis. However, there is not any conclusive evidence of association with the disease. Recently, the hypothesis of the opportunistic pathogen has emerged. Treatment has traditionally been based on met- ronidazole and other imidazoles. The recent obtaining of the nuclear genome will allow the rational development of new effective drugs. The aim of this review is to highlight the main epidemiological, clinical, pathogenic, diagnostic and therapeutic aspects of the Blastocystis infection. Corresponding author: José Ramón Vielma Guevara. Decanato de Ingeniería de Producción Animal. Apartado Pos- tal 4001, Maracaibo, República Bolivariana de Venezuela. Tel: +58-261-749-0444. Fax: +58-261-759-7247. E-mail: [email protected] 54 Vielma Blastocistosis: Aspectos epidemiológicos, clínicos, patogénicos, diagnósticos y terapéuticos. Invest Clin 2019; 60 (1): 53-78 Palabras clave: Blastocystis spp.; genotipos; epidemiología; síndrome de intestino irritable; urticaria; metronidazol. Resumen. Blastocystis es un stramenopile o cromista, pleomórfico, no mó- vil. Se han identificado diecinueve subtipos (genotipos) de este organismo. Tie- ne una distribución mundial. Las tasas de prevalencia en humanos son inferio- res al 1% en los países desarrollados, y hasta el 100% en los países en desarrollo. Se reconoce la transmisión fecal-oral, a través de la ingestión de alimentos y aguas contaminadas y la transmisión zoonótica. El diagnóstico se lleva a cabo mediante examen fecal directo, cultivo y técnicas moleculares. Blastocystis tie- ne factores de virulencia tales como proteasas de cisteína, proteasas de serina y legumaínas, principalmente secretadas a la interface patógeno-hospedador. Este stramenopile se ha relacionado con síntomas gastrointestinales, síndrome de intestino irritable, urticaria y artritis. Sin embargo, no hay pruebas conclu- yentes de asociación con la enfermedad. Recientemente, ha surgido la hipótesis de patógeno oportunista. El tratamiento tradicionalmente se ha basado en me- tronidazol y otros imidazoles relacionados. La reciente obtención del genoma nuclear permitirá el desarrollo racional de nuevas drogas efectivas. El objetivo de esta revisión es destacar los principales aspectos epidemiológicos, clínicos, patogénicos, diagnósticos y terapéuticos de la infección por Blastocystis. Recibido 06-06-2018 Aceptado 25-01-2019 INTRODUCTION 1% in developed countries to 100% in devel- oping countries (8, 9). The relatively recent Blastocystis spp. is a polymorphic organ- interest on Blastocystis, despite its descrip- ism; the vacuolar, granular, amoeboid, and tion a century ago is due to the belief that it cystic forms are the most frequent. Avacu- causes intestinal disease (10-13). olar, multivacuolar, and with filamentous in- The taxonomic classification of Blasto- clusions are also recognized forms (1-4). Al- cystis has been very controversial and wrong- though some authors consider that the cyst ly considered as plant material, fungus, flag- designation is not adequate because it is a ellate and protozoan (14, 15). In 1996, the chromist, other authors maintain that desig- molecular analysis of the small sub-unit of nation, which will be used in this review (4). the rRNA (SSU-rRNA) and elongation fac- However, its life cycle, sources, and trans- tor 1α, showed that Blastocystis could be in- mission mechanisms are not well known. cluded in the heterokontophyta (strameno- Its transmission occurs through a fecal-oral pile or chromista) category of eukaryotic route, by ingestion of contaminated water phylum, (16, 17). Later studies, using mul- and food, and zoonotic spread (5-7). This in- tiple molecular sequences of eight genes of fectious agent has a worldwide distribution Blastocystis, confirmed its taxonomic status and is the most prevalent stramenopile in as a stramenopile (18). This heterogeneous humans with prevalence rates from less than group includes unicellular and multicellular Investigación Clínica 60(1): 2019 Blastocystosis: Epidemiological, clinical, pathogenic, diagnostic, and therapeutic aspects 55 organisms, such as brown algae, diatoms, vis- countries where water and sewage treat- cous or mucilaginous elements, oomycetes ment systems, sanitary facilities, and stan- and aquatic molds (17, 18). One of the dis- dard housing developments are insufficient tinguishing features of stramenopile is the or lacking (31-34). Under these condi- presence of a flagellum, which gives mobility tions, Blastocystis cysts could spread readily at some stage of their life cycle; contradicto- through water supplies and distribution sys- rily, Blastocystis has no flagellum and is the tems and food (31-33). only stramenopile implicated as a causative Up to date, few epidemiological studies on agent of human disease (13, 19). the prevalence of Blastocystis in humans from Nineteen genotypes of Blastocystis have developed countries have been conducted. been identified (2). Denoeud et al. in 2011 Table I shows some of these reports (8, 30, 35- (20) obtained the nuclear genomic sequence 55) with prevalence values from 0.08% in Ger- of subtype 7 (ST7). This is the smallest stra- many (8) to 70.3% in the United States (35). menopile genome that has been sequenced, In many cases, participants included tourists, with 18.8 Mb. Blastocystis has a total of 6,020 immigrants, and refugees. These reports are genes, equivalent to 42% of its genome, very interesting because they evaluate the risk 24,580 exons or coding regions, 18,560 in- of the population of non-endemic areas for in- trons and 2,730 repeat regions. The genome fection. In a study of 7,677 patients in Paris, is compact and 25% of the information con- the prevalence of Blastocystis varied according sists of repetitions. The organism has a ma- to the population group studied: 17.4% in sub- nily anaerobic metabolism (20,21). jects free of any digestive tract disorders, 19.8% Blastocystis has been linked to human in adults with digestive tract disorders, and gastrointestinal disease, known as Blastocis- 13.8% in children (p<0.01) (56). tosis or Zierdt-Garavelli´s disease (11, 12). Table II summarizes some of the stud- In addition, this infectious agent has been as- ies conducted about the prevalence of Blas- sociated with irritable bowel syndrome (IBS), tocystis in humans from developing countries urticaria, ulcerative colitis, cancer and arthri- from 1990 to 2017. (9, 29, 31, 57-94), these tis (13, 22-25). Nevertheless, its pathogenic- values ranged from 3.4% in Nigeria (60) to ity is controversial (15, 26-28). In this sense, 100% in Senegal (9). it is important to highlight that until now, Cekin et al., conducted a study in 2012 most studies refer to a possible link and not (95) where 2334 patients with gastrointestinal a causal relationship. The statistical analyses symptoms composed the study group, which are based on statistics of independence and included 335 patients with diagnosed inflam- association between variables, without an matory bowel disease (IBS) and 877 with ir- adequate number of observations; therefore, ritable bowel syndrome (IBS). Patients with- they are partially conclusive. It is also impor- out any gastrointestinal symptoms or disease tant to clarify that there are well-designed (n =192) composed the control group. The studies that suggest a pathogenic role of Blas- mean ± standard deviation age of patients tocystis. The aim of this review is to highlight with IBS, patients with IBD, patients with gas- the most important epidemiological, clinical, trointestinal complaints and the control group pathogenic, diagnostic, and therapeutic as- were 45.8 ± 16.2, 45.2 ± 13.2, 47.3 ± 16.1, pects of the Blastocystis infection. and 45.5 ± 15.2 years old respectively with no statistically significant difference between EPIDEMIOLOGY groups (p =0.597). The groups were also com- parable to each other in terms of gender. In Prevalence in humans patients with gastrointestinal complaints, gen- The infection is widespread (7-9, 29, der distribution was homogenous in patients 30). The prevalence is higher in developing with (n =134; 83 (62%) females and 51 (38%) Vol. 60(1):