A paleoepidemiological approach to the challenging differential diagnosis of an isolated 1500-year-old anomalous molar from Panamá.

OBJECTIVE: This study seeks to quantify the presence and prevalence of specific genetic and infectious diseases in the pre-Colombian Panamanian population and uses these data to consider the plausibility of these diseases as causative factors in the development of an abnormal supernumerary cusp morphology in a 1500-year-old isolated molar recovered from Cerro Juan Díaz (Los Santos, Panama). MATERIALS: 267 individuals from pre-Columbian sites throughout Panama. METHODS: The anomalous tooth was analyzed through macroscopic, odontometric, and radiographic means. Tentative differential diagnosis was performed using inferences from paleopathological features of the broader regional population. RESULTS: The regional sample showed evidence of treponemal infection and developmental anomalies in 10.1% and 10.9% of individuals, respectively. CONCLUSIONS: While not able to rule out three potential genetic conditions, more evidence was found to support the differential diagnosis of congenital syphilis as the causative agent leading to the development of abnormal supernumerary cusps in the isolated molar. SIGNIFICANCE: This study demonstrates how characterizing disease experience in the population can assist in differential diagnoses at the individual level and cautions against the assumption that any one lesion in isolation is unique to only one specific pathological condition. LIMITATIONS: The timing discrepancy between clinical descriptions of congenital syphilis and genetic disorders, lack of knowledge on pathophysiological mechanisms of the former, poor preservation of Treponema pathogen ancient DNA, and deficiencies in modern public health data from Panama limit the differential diagnosis. SUGGESTIONS FOR FURTHER RESEARCH: Inclusion and serious contemplation of genetic diseases in paleopathological differential diagnoses is necessary.

Weaving Mitochondrial DNA and Y-Chromosome Variation in the Panamanian Genetic Canvas.

The Isthmus of Panama was a crossroads between North and South America during the continent's first peopling (and subsequent movements) also playing a pivotal role during European colonization and the African slave trade. Previous analyses of uniparental systems revealed significant sex biases in the genetic history of Panamanians, as testified by the high proportions of Indigenous and sub-Saharan mitochondrial DNAs (mtDNAs) and by the prevalence of Western European/northern African Y chromosomes. Those studies were conducted on the general population without considering any self-reported ethnic affiliations. Here, we compared the mtDNA and Y-chromosome lineages of a new sample collection from 431 individuals (301 males and 130 females) belonging to either the general population, mixed groups, or one of five Indigenous groups currently living in Panama. We found different proportions of paternal and maternal lineages in the Indigenous groups testifying to pre-contact demographic events and genetic inputs (some dated to Pleistocene times) that created genetic structure. Then, while the local mitochondrial gene pool was marginally involved in post-contact admixtures, the Indigenous Y chromosomes were differentially replaced, mostly by lineages of western Eurasian origin. Finally, our new estimates of the sub-Saharan contribution, on a more accurately defined general population, reduce an apparent divergence between genetic and historical data.

An isthmus of isolation: The likely elevated prevalence of genetic disease in ancient Panama and implications for considering rare diseases in paleopathology.

OBJECTIVE: This study considers the evidence for elevated frequencies of "rare" diseases in ancient Panama. Indications of population isolation by multidisciplinary sources allow for the possibility that rare inherited conditions may have been maintained at relatively high prevalences in the region due to gene flow restriction. MATERIALS: A sample of 267 skeletal human remains with diverse demographical characteristics from Pre-Columbian archaeological sites throughout Panama. METHODS: Remains were analyzed macroscopically and hard tissue developmental anomalies were documented. RESULTS: Frequencies of developmental anomalies and hard tissue changes consistent with specific rare genetic diseases, such as osteogenesis imperfecta, on the comparatively few human remains recovered from pre-Columbian archaeological sites are elevated as compared with global averages. CONCLUSIONS: The paleopathological evidence is concordant with a scenario of isolation in Pre-Columbian times and with an increased presence of genetic disorders in the population. SIGNIFICANCE: This study advocates for the special consideration of rare diseases by paleopathologists in regions where populations may have experienced prolonged geographical or social isolation in the past. LIMITATIONS: A dearth of local modern epidemiological data and low sample sizes of preserved human remains in certain regions of the country limited the possibilities of spatiotemporal comparisons of rare disease prevalence. SUGGESTIONS FOR FURTHER RESEARCH: Further scrutiny of developmental anomalies of genetic origin on ancient Panamanian remains and biomolecular testing of remains for specific disorders should be pursued to confirm the findings of this study.

Cold-water diving in the tropics? External auditory exostoses among the pre-Columbian inhabitants of Panama.

OBJECTIVES: The appearance of external auditory exostoses archaeologically has been attributed to aquatic activities in middle latitudes. However, recent clinical research implicates low sea surface temperatures, especially below a threshold of 19°C, as a stronger predictor of ear exostosis development than latitude. Here, we examine the frequency of external auditory exostoses in human remains from nine pre-Columbian archaeological sites in Panama, representing individuals from a warm, tropical region. MATERIALS AND METHODS: External auditory exostoses were recorded as present when an abnormal bony growth was observed macroscopically within the ear canal. The presence of exostoses was compared by right and left side, geographical region, sex, and degree of stenosis. RESULTS: A total of 125 adult individuals made up the observable sample analyzed in this study. Exostoses were observed in seven males and one female. All individuals affected by this pathology were excavated from mortuary contexts along the Gulf of Panama-a region characterized by intense cold water upwelling in the dry season. DISCUSSION: This study suggests that external auditory exostoses in pre-Columbian Panama affected individuals involved in habitual aquatic activities in the cold, upwelled waters of the Gulf of Panama. These activities appear to be almost exclusively dominated by male individuals. Ethnohistorical and archaeological records point to marine shell resource acquisition by deep-water diving as the activity driving exostosis development in pre-Columbian Panama.

A probable primary malignant bone tumor in a pre-Columbian human humerus from Cerro Brujo, Bocas del Toro, Panamá.

We present a rare case of primary bone cancer principally affecting the right humerus of a skeleton from the pre-Columbian site of Cerro Brujo (1265-1380 CE) in Bocas del Toro, on the Caribbean coast of Panamá, excavated in the early 1970s. The humerus contains a dense, calcified sclerotic mass with associated lytic lesions localized around the midshaft of the diaphysis. Evidence of systemic inflammation and anemia, likely caused by the cancer, are visible in the form of severe porotic hyperostosis of the cranial vault and bilateral periosteal reactions in the tibiae. Differential diagnosis and future probes of the tumor are discussed. A tooth from the individual yielded a radiocarbon date 150 years later than those of the domestic occupation at the site. Given that it was the only formal burial recovered from the site, and as the individual had such a visible, painful, and rare pathology, this likely constitutes a ritual burial.

The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections.

OBJECTIVES: Recent studies in paleopathology have shown promise in associating some skeletal lesions with malarial infection. However, malaria's skeletal manifestation has never been confirmed using a large clinical reference sample from an endemic area for malaria with known individual causes of death. MATERIALS AND METHODS: To pinpoint evidence of malaria infection on ancient skeletal remains, this study uses an epidemiological approach to compare skeletal lesions in a modern reference sample of 98 individuals from Uganda, where malaria is holoendemic, to a similar modern sample of 106 individuals from a malaria-free area. RESULTS: Five porous skeletal lesions are identified that appear more frequently in the endemic area population, especially in anemic individuals. These appear on the cranium, vertebral column, and humeral and femoral necks. Periostitis also associates strongly with individuals in the endemic population; however, linear enamel hypoplasias show an inverse association. The identified lesions are tested for their association with each other, and then tested individually for their diagnostic power through measures of sensitivity and specificity. A diagnostic outcome algorithm is formed from the remaining skeletal lesions and their inter-lesion associations. DISCUSSION: Several etiological explanations for the characteristic malarial skeletal lesions are explored, including severe malarial anemia, an imbalance in bone remodeling, and extramedullary erythropoiesis. The importance of careful differential diagnoses between other infectious and noninfectious causes of these lesions is discussed, including the potential for coinfection of malaria with other infectious diseases. The findings of this study are pivotal in establishing diagnostic criteria by which we can identify the prevalence and impact of malaria on past populations.

Cribra orbitalia in the ancient Nile Valley and its connection to malaria.

Cribra orbitalia is a common skeletal lesion found on ancient human remains excavated from the Nile Valley. Recent etiological research implicates hemolytic anemia as a main factor leading to the formation of cribra orbitalia. Further, an association between the hemolytic anemia caused by malaria and cribra orbitalia has been demonstrated. The presence of malaria in the ancient Nile Valley has been verified directly through genetic and immunologic studies of Egyptian mummies, but its prevalence and spread remain unknown. As some models have pointed to the Nile Valley as the pathway of malarial dispersion during the Egyptian Dynastic period, variability in cribra orbitalia rates should provide a way to track the disease spread. This study surveyed cribra orbitalia frequencies at 29 ancient Nile Valley sites, representing 4760 individuals ranging from prehistoric to Christian periods and situated between the 3rd Cataract and Nile Delta. Results showed high cribra orbitalia rates, with an overall mean of 42.8% of the total population affected. Over time and space, the data showed no significant correlation, suggesting high levels of anemia affected individuals in the Nile Valley equally from late pre-dynastic to Christian periods. These findings suggest widespread endemic malaria in the Nile Valley before Dynastic Egypt.