Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.

The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans. Reports from 15 individuals have described RFX-associated phenotype as a neurobehavioural disease, manifesting primarily with global developmental delay and intellectual disability. Autism spectrum disorder and attention deficit hyperactivity disorder have also been described in some children. Here we report a case of a 19-month-old with a de novo missense variant in RFX7 resulting in severe global developmental delay including significant speech delay, microcephaly, dyskinetic movements, and failure to thrive. This is the first association between variants in RFX7 and failure to thrive, expanding the phenotype of this newly described gene. In this report we will also show RFX7 associated progressive central nervous system involvement through serial brain imaging.

Gastrointestinal infection in Italy during the Roman Imperial and Longobard periods: A paleoparasitological analysis of sediment from skeletal remains and sewer drains.

OBJECTIVE: This study aims to investigate parasitic infection in Italy during the Roman period (27 BCE-476 CE) and subsequent Longobard (Lombard) period (6th-8th CE). MATERIALS: Sediment samples from drains and burials from Roman Imperial-period sites in Italy (Lucus Feroniae, Oplontis, Vacone, and Vagnari), Late Antique and Longobard-period burials at Selvicciola (ca. 4th-8th CE), and Longobard-period burials at Vacone and Povegliano Veronese. METHODS: Microscopy was used to identify helminth eggs and enzyme-linked immunosorbent assay (ELISA) to detect protozoan antigens. RESULTS: Roundworm and whipworm were found in pelvic sediment from Roman-period burials, while roundworm and the protozoan Giardia duodenalis were identified in Roman-period drains. In pelvic sediment from the Late Antique through Longobard periods, roundworm and Taenia tapeworm eggs were identified. CONCLUSIONS: Fecal-oral parasites were found throughout Imperial Roman Italy, suggesting that gastrointestinal infections caused a significant disease burden. In the Longobard period we see continuity in transmission of fecal-oral parasites, and the appearance of zoonotic parasites acquired from eating undercooked meat. SIGNIFICANCE: A wealth of information exists about certain diseases in the Roman period, but relatively little is known about intestinal parasites in Italy during the Roman and Longobard periods. This is the first evidence for Giardia in Roman period Italy, and for any parasites in the Longobard period in Italy. LIMITATIONS: Low egg concentrations and lack of controls for some samples makes it difficult to differentiate true infections from environmental contamination in some cases. SUGGESTIONS FOR FUTURE RESEARCH: Continual study of samples from Roman and Longobard period Italy.

A comparative study of parasites in three latrines from Medieval and Renaissance Brussels, Belgium (14th-17th centuries).

The aim of this study is to determine the species of parasite that infected the population of Brussels during the Medieval and Renaissance periods, and determine if there was notable variation between different households within the city. We compared multiple sediment layers from cesspits beneath three different latrines dating from the 14th-17th centuries. Helminths and protozoa were detected using microscopy and enzyme-linked immunosorbent assay (ELISA). We identified Ascaris sp., Capillaria sp., Dicrocoelium dendriticum, Entamoeba histolytica, Fasciola hepatica, Giardia duodenalis, Taenia sp. and Trichuris sp. in Medieval samples, and continuing presence of Ascaris sp., D. dendriticum, F. hepatica, G. duodenalis and Trichuris sp. into the Renaissance. While some variation existed between households, there was a broadly consistent pattern with the domination of species spread by fecal contamination of food and drink (whipworm, roundworm and protozoa that cause dysentery). These data allow us to explore diet and hygiene, together with routes for the spread of fecal-oral parasites. Key factors explaining our findings are manuring practices with human excrement in market gardens, and flooding of the polluted River Senne during the 14th-17th centuries.

Intestinal parasites at the Late Bronze Age settlement of Must Farm, in the fens of East Anglia, UK (9th century B.C.E.).

Little is known about the types of intestinal parasites that infected people living in prehistoric Britain. The Late Bronze Age archaeological site of Must Farm was a pile-dwelling settlement located in a wetland, consisting of stilted timber structures constructed over a slow-moving freshwater channel. At excavation, sediment samples were collected from occupation deposits around the timber structures. Fifteen coprolites were also hand-recovered from the occupation deposits; four were identified as human and seven as canine, using fecal lipid biomarkers. Digital light microscopy was used to identify preserved helminth eggs in the sediment and coprolites. Eggs of fish tapeworm (Diphyllobothrium latum and Diphyllobothrium dendriticum), Echinostoma sp., giant kidney worm (Dioctophyma renale), probable pig whipworm (Trichuris suis) and Capillaria sp. were found. This is the earliest evidence for fish tapeworm, Echinostoma worm, Capillaria worm and the giant kidney worm so far identified in Britain. It appears that the wetland environment of the settlement contributed to establishing parasite diversity and put the inhabitants at risk of infection by helminth species spread by eating raw fish, frogs or molluscs that flourish in freshwater aquatic environments, conversely the wetland may also have protected them from infection by certain geohelminths.

Intestinal parasites in six Islamic medieval period latrines from 10th-11th century Córdoba (Spain) and 12th-13th century Mértola (Portugal).

OBJECTIVE: To investigate the types of intestinal parasites that infected people living in Islamic period southern Iberia (al-Andalus), and compare with other regions of Europe. MATERIALS: Four cesspits from 10th-11th century CE Córdoba (Spain), and two from 12th-13th century Mértola (Portugal). METHODS: Sediment from each cesspit was analyzed using digital light microscopy and enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis revealed eggs of roundworm (Ascaris lumbricoides) in every cesspit analyzed, but no evidence of other species of helminth or protozoal parasites. CONCLUSION: Differences were noted between parasite species found in Mediterranean Europe and northern Europe, where a range of zoonotic parasites were endemic alongside sanitation-related parasites. We suggest that the scarcity of zoonotic parasites in southern Europe in the medieval period may reflect contrasts in climate between northern and southern Europe. SIGNIFICANCE: The repeated identification of roundworm eggs suggests that al-Andalus was less hygienic than historically depicted. We did not note a difference between parasites found in Muslim and Christian regions of Iberia, and the predominance of parasites spread by fecal contamination of food is consistent with past research. LIMITATIONS: The eggs of some species of parasite are fragile, so may theoretically have been present in the population but did not survive for us to identify them. SUGGESTIONS FOR FURTHER RESEARCH: To further investigate the role of climate upon the parasites that affected past human populations.

Intestinal Parasites in an Ottoman Period Latrine from Acre (Israel) Dating to the Early 1800s CE.

The aim of this study is to determine the species of parasites that affected the inhabitants of the city of Acre on the coast of the eastern Mediterranean during the Ottoman Period. This is the first archaeological study of parasites in the Ottoman Empire. We analysed sediment from a latrine dating to the early 1800s for the presence of helminth eggs and protozoan parasites which caused dysentery. The samples were examined using light microscopy and enzyme-linked immunosorbent assay (ELISA) kits. We found evidence for roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), fish tapeworm (Dibothriocephalus sp.), Taenia tapeworm (Taenia sp.), lancet liver fluke (Dicrocoelium dendriticum), and the protozoa Giardia duodenalis and Entamoeba histolytica. The parasite taxa recovered demonstrate the breadth of species present in this coastal city. We consider the effect of Ottoman Period diet, culture, trade and sanitation upon risk of parasitism in this community living 200 years ago.

Intestinal parasites from the 2nd-5th century AD latrine in the Roman Baths at Sagalassos (Turkey).

The aim of this research was to determine the species of intestinal parasite present in a Roman Imperial period population in Asia Minor, and to use this information to improve our understanding of health in the eastern Mediterranean region in Roman times. We analyzed five samples from the latrines of the Roman bath complex at Sagalassos, Turkey. Fecal biomarker analysis using 5ß-stanols has indicated the feces were of human origin. The eggs of roundworm (Ascaris) were identified in all five samples using microscopy, and the cysts of the protozoan Giardia duodenalis (which causes dysentery) were identified multiple times in one sample using ELISA. The positive G. duodenalis result at Sagalassos is particularly important as it represents the earliest reliable evidence for this parasite in the Old World (i.e. outside the Americas). As both these species of parasite are spread through the contamination of food and water by fecal material, their presence implies that Roman sanitation technologies such as latrines and public baths did not break the cycle of reinfection in this population. We then discuss the evidence for roundworm in the writings of the Roman physician Galen, who came from Pergamon, another town in western Asia Minor.