Evidence of tungiasis in pre-Hispanic America.

Ancient parasites of the genus Tunga originated in America and, during the first half of the 19th century, were transported to the Eastern Hemisphere on transatlantic voyages. Although they were first documented by Spanish chroniclers after the arrival of Columbus, little is known about their presence in pre-Hispanic America. To evaluate the antiquity of tungiasis in America, we assessed several kinds of early documentation, including written evidence and pre-Incan earthenware reproductions. We identified 17 written documents and 4 anthropomorphic figures, of which 3 originated from the Chimu culture and 1 from the Maranga culture. Tungiasis has been endemic to Peru for at least 14 centuries. We also identified a pottery fragment during this study. This fragment is the fourth representation of tungiasis in pre-Hispanic America identified and provides explicit evidence of disease endemicity in ancient Peru.

Triclabendazole for the treatment of human fascioliasis and the threat of treatment failures.

INTRODUCTION: The only drug effective against the infection caused by Fasciola hepatica or F. gigantica is triclabendazole (TCBZ), recommended by the WHO and recently approved by the FDA. Here, we describe the evolution of TCBZ regimens and the emergence of TCBZ failure to Fasciola infection. AREAS COVERED: The present review focuses on the evidence of TCBZ for the treatment of fascioliasis. For acute fascioliasis, there is a lack of studies to measure the presence of eggs of Fasciola in stool samples on the follow-up after initial TCBZ treatment. For chronic fascioliasis, WHO recommends a single oral dose of TCBZ 10 mg/kg whereas CDC recommends two doses of TCBZ 10 mg/kg 12 h apart. Incremental number of treatment failures have been documented worldwide. There are currently no therapeutic alternatives for the treatment of fascioliasis in humans. EXPERT OPINION: Most cases of human fascioliasis are successfully treated with TCBZ, but some continue excreting eggs in the stools despite 1-2 standard of care regimens of TCBZ. A precise regimen is unclear for those patients who fail the initial treatment with TCBZ. Further clinical trials are needed to address the possible TCBZ emerging resistance.

Observational study on the effectiveness and safety of multiple regimens of triclabendazole in human fascioliasis after failure to standard-of-care regimens.

OBJECTIVES: Triclabendazole (TCBZ) is the recommended anthelmintic against Fasciola hepatica at a dose of 10 mg/kg body weight administered as a single or double dose. However, treatment failures to TCBZ standard-of-care (SOC) doses have been reported in humans. The aim of this study was to describe the effectiveness and tolerability of alternative TCBZ regimens in those patients who failed the SOC regimen for fascioliasis in Peru. METHODS: A retrospective study was conducted at a major referral centre for fascioliasis in Peru between 2002 and 2018. Inclusion criteria were cases with chronic F. hepatica infection who failed the SOC regimen for human fascioliasis with TCBZ at 10 mg/kg orally as single dose with food. RESULTS: A total of 27 cases (59% female; mean age 39.4 years, range 6-71 years) with chronic fascioliasis failed at least once the current SOC regimen of TCBZ. Of 27 cases, 21 failed a second treatment regimen. Multiple regimens of TCBZ were given to these patients until three consecutive stool examinations were negative for Fasciola eggs. The overall cure rate was 74%. TCBZ was well tolerated with minimal side effects. CONCLUSION: According to the results of this study, patients labelled as having 'TCBZ resistance' may respond to multiple regimens of TCBZ with a cure rate of 74%. Thus, the term 'TCBZ resistance' should be re-evaluated using biomarkers.

Human herpesvirus 8 genotype E in patients with Kaposi sarcoma, Peru.

To determine human herpesvirus 8 (HHV-8) K1 genotypes in patients with Kaposi sarcoma (KS) from Peru, we characterized HHV-8 in 25 KS biopsy samples. Our findings of 8 A, 1 B, 14 C, and 2 E subtypes showed high HHV-8 diversity in these patients and association between E genotype and KS development.

Evaluation of Fas2-ELISA for the serological detection of Fasciola hepatica infection in humans.

The performance of Fas2-ELISA for the diagnosis of Fasciola hepatica infection in children living in areas of high endemicity for fascioliasis in the Peruvian Andes is analyzed. Fas2-ELISA is based on the detection of circulating IgG antibodies elicited in infected individuals against a F. hepatica antigen termed Fas2. The study was conducted in three Andean localities, Huertas-Julcan in Junin, Asillo in Puno, and Cajamarca, with a total population of 634 children in an age range 1 to 16 years old. Child fascioliasis prevalence was 21.1% in Huertas-Julcan, 25.4% in Asillo, and 24% in Cajamarca, estimated by coprological inspection. The seroprevalence of F. hepatica infection, determined by Fas2-ELISA, was 27.8% in Huertas-Julcan, 44.6% in Asillo, and 29.1% in Cajamarca. The overall sensitivity of Fas2-ELISA was 92.4%, the specificity 83.6%, and the negative predictive value 97.2%. No association between OD(450) Fas2-ELISA and infection intensity measured by egg counting was observed. Results show that Fas2-ELISA is a highly sensitive immunodiagnostic test for the detection of F. hepatica infection in children living in human fascioliasis endemic areas.

Preliminary antigenic characterisation of an adult worm vomit preparation of Fasciola hepatica by infected human sera.

Fascioliasis is an emerging/re-emerging vector-borne disease with the widest known distribution. Approximately 17 million people are infected around the world, being the Andean region the most affected area. There is an important necessity to develop sensitive and specific diagnostic tools to treat patients early and to avoid complications. In this paper we evaluated the immune response of infected humans against two antigenic preparations: the total soluble extract (FhTSE) and the adult worm vomit (FhAWV) in order to identify antigenic fractions specific for Fasciola hepatica. Both preparations were processed by SDS-PAGE and Western blot with human sera with fascioliasis (F), other parasitosis and healthy individuals. In the immunoblot of FhTSE, sera F recognised 16 bands with MW between eight and 110 kDa, from which those of 8, 9, 10, 38, 45 and 57 kDa were specific. In the preparation FhAWV, sera F recognised nine bands with MW from eight to 85 kDa, from which those of 8, 12, 15 and 24 kDa were specific. Some bands of cross-reaction were evident with sera from patients with other parasitoses, more frequent with the FhTSE. Bands within the MW mentioned, particularly that of eight kDa, have been shown to be specific by others, and deserve additional characterisation for their potential use in immunodiagnosis.

Is classic Kaposi's sarcoma endemic in Peru?: report of a case in an indigenous patient.

Kaposi's sarcoma (KS) has been classified in four clinical variants (classic or Mediterranean; endemic or African; epidemic or AIDS-related; iatrogenic or immunosuppression-related). Human herpesvirus 8 (HHV-8), has been found in all these variants. We herein discuss the unusual presentation of a 53-year-old indigenous patient with purplish-brown nodular lesions on lower extremities, and miliary tuberculosis. ELISA-HIV tests were negative and immunohistochemistry (IHC) of the tumor tissue was positive for HHV-8. This is the first reported case in which the presence of HHV-8 was evidenced by means of IHC techniques in Peru. We also review all available Peruvian literature of classic KS, a disease that has been frequently reported in indigenous population of Peru since 1968, making this country a possible endemic zone of classic KS.

Risk factors for Fasciola hepatica infection in children: a case-control study.

We conducted a case-control study to clarify the risk factors for human fascioliasis in the Northern Peruvian Altiplano. Cases (n=61) were individuals who were diagnosed as having chronic fascioliasis by faecal and/or serologic (Fas2-ELISA) studies. Controls (n=61) had negative serologic and coprological results for Fasciola hepatica. We identified an association between fascioliasis and four variables (40 analysed): the habit of drinking alfalfa juice (OR=4.5; 95% CI 1.8-11.1; P<0.001); familiarity with aquatic plants (OR=4.3; 95% CI 1.8-10.6; P<0.001); dog ownership (OR=5; 95% CI 1.7-15.1; P=0.002); and raising more than five sheep (OR=0.3; 95% CI 0.1-0.8; P=0.01). According to clinical presentation and laboratory studies, dizzy spells (P=0.01), history of jaundice (P=0.01), peripheral eosinophilia (P=0.005) and Ascaris lumbricoides in stools (P=0.001) were associated with fascioliasis. The principal exposure factor for F. hepatica infection was drinking alfalfa juice. In conclusion, we suggest that human fascioliasis in Peru should be suspected in patients from livestock-rearing areas, who present with recurrent episodes of jaundice and who have a history of consumption of alfalfa juice or aquatic plants, or who have eosinophilia.

Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review.

BACKGROUND: Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. METHODOLOGY AND PRINCIPAL FINDINGS: A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. CONCLUSIONS: Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans.

Epidemiology and clinical characteristics of classic Kaposi's sarcoma, seroprevalence, and variants of human herpesvirus 8 in South America: a critical review of an old disease.

OBJECTIVE: To review the current South American literature on classic Kaposi's sarcoma (KS) and human herpesvirus 8 (HHV-8), and point the way for studies that still need to be performed. MATERIALS AND METHODS: The authors performed an exhaustive search in LILACS, SCIELO and PUBMED databases for classic KS and HHV-8 in South America. The relevant material was evaluated and reviewed. RESULTS: More than 250 cases have been reported with three big case series (Argentina, Colombia and Peru). The classic KS form seen in Colombia resembles the type of disease seen among African communities; the same unusual presentation with confluent exophytic nodules or eroded lesions has been noticed in Peru. Low rates of HHV-8 antibodies have been found in blood donors from Chile, Argentina and Brazil (3%, 4%, 2.8-7.4%, respectively); whereas high rates of HHV-8 antibodies have been found in Amerindians from Brazil and Ecuador. Five specimens from Argentina were subtyped: (three classic KS and two AIDS KS); the identified strains fell into subtypes A and C. AIDS-related KS specimens from Brazil and Venezuela were subtyped: (43 and nine respectively); analysis grouped them predominantly into subgroups A, B and C. A new HHV-8 subtype E was found endemic in Brazilian and Ecuadorian Amerindians. In French Guiana ten endemic KS and six AIDS-related KS specimens were subtyped; analysis grouped them predominantly into subgroups A, B and C. CONCLUSION: Classic KS in South America has a very similar clinical presentation but not the same as the classic KS variety described in the Mediterranean. Initial seroprevalence studies performed in the general population and in blood donors showed low seroprevalence of HHV-8, whereas high seroprevalence rates were seen in Amerindian population. The existing serological assays, nonetheless, need to be further refined, and new assays need to be developed. Finally, the key to understanding the precise molecular epidemiology and phylogenetic distribution of HHV-8 in South America would be to perform more subtyping of classic KS cases.

Fascioliasis in relatives of patients with Fasciola hepatica infection in Peru.

High prevalence rates of human fascioliasis have been described in several regions of Peru. We surveyed 20 families in an endemic area of Peru in order to determine the proportion of infection with F. hepatica in relatives of diagnosed subjects and in order to identify associated risk factors. The study included feces and blood samples of 93 subjects. Ages ranged from one to 53 (mean = 18.6; SD = 14.2). The overall prevalence of fascioliasis by fecal examinations was 33.3% (n = 83) and by serology, 51.9% (n = 86). The prevalence in age group I (< or = 19 years old) by coprological and serological tests was 61.4% and 75.9%, respectively; in group II (> 19 years old) 15.4% and 37.5%. The main associated risk factor with fascioliasis was eating salads (OR = 3.29, CI = 1.2 - 9.0, p = 0.02). In conclusion, human fascioliasis is highly prevalent in the relatives of index cases and the most significant risk factor of acquiring fascioliasis in the family is eating salads in endemic areas.

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children.

INTRODUCTION: The therapeutic scheme of triclabendazole (TCBZ), the recommended anthelmintic against Fasciola hepatica , involves 10mg/kg of body weight administered in a single dose; however, clinical trials in children are scarce. We evaluated the efficacy and tolerability of 2 schemes of TCBZ. METHODS: Eighty-four Peruvian children with F. hepatica eggs in their stools were allocated into 2 groups: 44 received 2 dosages of 7.5mg/kg each with a 12-h interval (Group I), and 40 received a single 10-mg/kg dose (Group II). Evaluation of efficacy was based on the presence of eggs in stools, and tolerability was based on the presence of symptoms and signs post-treatment. RESULTS: A parasitological cure was obtained in 100% of individuals from Group I and 95% of individuals from Group II. The most common adverse event was biliary colic. CONCLUSIONS: The tested scheme was efficacious and tolerable, and it might be an optimal scheme in the region. To the best of our knowledge, this represents the largest series of children treated with TCBZ in a non-hospital setting.

Carrion's disease (Bartonellosis bacilliformis) confirmed by histopathology in the High Forest of Peru.

Bartonellosis or Carrion's disease is endemic in some regions of Peru, classically found in the inter-Andean valleys located between 500 and 3200 meters above sea level. We report the case of a 43 year-old male patient, farmer, who was born in the Pichanaki district (Chanchamayo, Junin), located in the High Forest of Peru. He presented with disseminated, raised, erythematous cutaneous lesions, some of which bled. The distribution of these lesions included the nasal mucosa and penile region. Additionally subcutaneous nodules were distributed over the trunk and extremities. Hematologic exams showed a moderate anemia. Serologic studies for HIV and Treponema pallidum were negative. The histopathologic results of two biopsies were compatible with Peruvian wart. Oral treatment with ciprofloxacin (500 mg BID) was begun. Over 10 days, the patient showed clinical improvement. This is the first report of a confirmed case of bartonellosis in the eruptive phase originating from the Peruvian High Forest, showing the geographical expansion of the Carrion's disease.

Histopathological features of tungiasis in Peru.

Tungiasis is an ectoparasitic skin disease caused by Tunga penetrans and Tunga trimamillata. There is a lack of histopathological studies that evaluate the recognition of this flea in tissues. We describe the ex vivo dermoscopic and the histopathological patterns of six cases and relate the findings to the developmental stage of the parasite as defined by the Fortaleza classification: two were classified as Fortaleza 3b, 3 as 4a, and 1 as 4b. Two dermoscopic patterns were observed: a brown pigmented ring and a radial crown with a central pore. The most common histopathological findings were an eosinophilic cuticle, eggs in different stages of development, tracheal rings (parasite), and basal hyperplasia (host). The eosinophilic cuticle, eggs in different stages of evolution, and tracheal rings can help to establish the diagnosis when other parts of the parasite are lacking. The Fortaleza staging may represent a tool for pathology reporting purposes.

Fasciola hepatica phenotypic characterization in Andean human endemic areas: valley versus altiplanic patterns analysed in liver flukes from sheep from Cajamarca and Mantaro, Peru.

Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica. Of both species, F. hepatica is the only one described in the Americas, mainly transmitted by lymnaeid snail vectors of the Galba/Fossaria group. Human fascioliasis endemic areas are mainly located in high altitude areas of Andean countries. Given the necessity to characterize F. hepatica populations involved, the phenotypic features of fasciolid adults infecting sheep present in human fascioliasis endemic areas were analysed in the Cajamarca Valley and Mantaro Valley (valley transmission patterns) and the northern Bolivian Altiplano (altiplanic transmission pattern). A computer image analysis system (CIAS) was applied on the basis of standardized measurements. The aforementioned highland populations were compared to standard lowland natural and experimental populations of European origin. Liver fluke size was studied by multivariate analyses. Two phenotypic patterns could be distinguished in F. hepatica adult size: the valley pattern (Cajamarca and Mantaro, Peru) and the altiplanic pattern (northern Altiplano, Bolivia). Results showed that the Andean valley population and European standard populations presented a phenotypic homogeneity. The Altiplano population showed a large size range with a pronouncedly lower minimum size indicating that uterus gravidity is reached at a smaller size than in valley populations. The results of this study demonstrate that there is no apparent relationship between the shape of fasciolid adults with regard to altitudinal difference or geographical origin and that allometry-free shape appears as a more stable trait than size in fasciolid species. Results are analysed in terms of intensity/crowding effect aspects and permanent/seasonal transmission characteristics.

An ectopic case of Tunga spp. infection in Peru.

Tungiasis is a neglected ectoparasitism of impoverished areas in South America and sub-Saharan Africa. The sand flea Tunga spp. preferably infests the soles and the periungueal and interdigital regions of the feet. Ectopic tungiasis is rare, even in highly endemic areas. We describe a case of an indigenous patient in Peru who presented with a nodular lesion in the extensor aspect of the knee and whose biopsy was compatible with Tunga spp. This is the first documented case of knee tungiasis in an endemic country. The historical, clinical, histological, and current epidemiological aspects of tungiasis in Peru are discussed here.

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children

The therapeutic scheme of triclabendazole (TCBZ), the recommended anthelmintic against Fasciola hepatica , involves 10mg/kg of body weight administered in a single dose; however, clinical trials in children are scarce. We evaluated the efficacy and tolerability of 2 schemes of TCBZ.