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Pharmacogenomic diversity in Amazonian Indigenous populations: implications for Berlin-Frankfurt-Münster acute lymphoblastic leukemia therapy.

PURPOSE: This study aimed to characterize pharmacogenomic variation in genes involved in the metabolism and transport of drugs used in Berlin-Frankfurt-Münster-based therapy in Amazonian Indigenous individuals and to compare allele frequencies with major continental populations. METHODS/PATIENTS: Whole-exome sequencing data previously generated from 64 healthy Indigenous individuals from 12 Amazonian ethnic groups were analyzed. A total of 120 genes associated with drugs used in Berlin-Frankfurt-Münster protocols were selected. Variants were annotated and filtered using bioinformatic quality-control criteria, and allele frequencies were compared with African, Admixed American, East Asian, European, and South Asian populations from the 1000 Genomes Project. Multidimensional scaling was used to assess population-level genetic similarity. RESULTS: After quality control, 648 variants were identified. Twenty-eight variants were observed exclusively in the Indigenous study population, including four nonsynonymous coding variants with moderate predicted impact. Significant allele-frequency differences were observed for ADA rs11555566, CBR3 rs881711, and CYP2B6 rs3745274; rs881711 and rs3745274 differed from all five reference populations. Multidimensional scaling showed a distinct Indigenous pharmacogenomic profile, with greater similarity to the Admixed American population. CONCLUSIONS: Amazonian Indigenous populations exhibit substantial pharmacogenomic diversity in genes relevant to Berlin-Frankfurt-Münster-based therapy. These findings identify candidate variants for functional and clinical validation and reinforce the importance of including underrepresented populations in pharmacogenomic research.

Acute lymphoblastic leukemia↗

Health and demography of native Amazonians: historical perspective and current status.

Native Amazonians have been the victims of two massive historical assaults, one at the time of the Conquest and the other during the Twentieth century. Due to epidemic disease and environmental destruction, many tribes have gone from contact to displacement, decimation, and extinction in a single generation. Deculturation and the construction of large development projects have had catastrophic effects on native populations. In many ways, native Amazonians have experienced a reverse of the "Epidemiologic Transition". Paradoxically, one of the effects of cultural disruption for some native Amazonians has been the loss of cultural controls on fertility with the result that high fertility has become a major health problem. Combined with rapid growth of non-indigenous Amazonian populations, deforestation, and urbanization, native Amazonians face grave obstacles to long-term survival.

Journal Article↗

Prevalence of pterygium and cataract in indigenous populations of the Brazilian Amazon rain forest.

PURPOSE: To compare the prevalence of pterygium and cataract in four indigenous populations of the Brazilian Amazonian rain forest (Arawak, Tukano, Maku, and Yanomami) with different ethnic and social behaviour backgrounds. METHODS: A cross-sectional pterygium and cataract survey was performed in 624 adult Indians of the Brazilian rain forest belonging to four different ethnic groups. The Indians were classified according to their social behaviour in two groups: Arawak and Tukano (group 1) and Maku and Yanomami (group 2). Slit-lamp biomicroscopy was employed to examine the entire sample. All subjects were classified as 1 or 0 according to the presence or absence pterygium and cataract. Sex and age were also recorded. RESULTS: chi(2)-tests revealed that the prevalence of pterygium and cataract differed significantly between groups 1 and 2. For pterygia: 36.6% (97/265) and 5.0% (18/359), respectively (chi(2)=101.2, P<0.0001), and for cataracts: 24.5% (65/265) and 13.7% (49/359) respectively (chi(2)=12.09, P=0.0005). Gender was not associated with pterygium (P=0.1326) and cataract (P=0.2263) in both groups. Elderly subjects showed a significantly higher prevalence of cataract (P<0.0001). The prevalence of pterygia did not increase with age (P=0.8079) in both groups. CONCLUSION: Indians of group 1 have higher prevalence of pterygia and cataract than Indians of group 2. Social behaviour, especially the rate of sun exposure, appears to be the main factor for the different rates of pterygium and cataract displayed by these indigenous people of the Brazilian rain forest.

Adult↗

Beriberi in a well-nourished Amazonian population.

Beriberi is an endemic disease among the Naporuna indigenous people of Ecuadorean Amazonia (annual morbidity rate of 1.5%). A total of 47 patients with dry beriberi were seen at the Franklin Tello Hospital, Napo, during 1995-1996; a similar incidence was observed in previous years. No wet beriberi was found. Although the diagnosis of the disease was made clinically, an effective and quick response to thiamine treatment excluded other differential diagnoses, such as tropical ataxic neuropathy. Although indigenous people have several possible dietetic risk factors, none of them adequately explain the disease's high incidence. Some suggestions are made for the high incidence of beriberi among this Amazonian people but its cause remains unknown.

Adolescent↗

[The national census and indigenous Amazonian groups].

The author uses data from the 1981 Peruvian census to determine the size and characteristics of the indigenous population of the Amazon region. "The document includes a series of graphs and tables comparing ethnic group, province and district categories, which could constitute a first data base and an important source of comparison with information coming from the recent (1993) census." (SUMMARY IN ENG)

Americas↗

Tuberculin reactivity and tuberculosis epidemiology in the Pakaanóva (Wari') Indians of Rondônia, south-western Brazilian Amazon.

OBJECTIVE: To investigate the characteristics of tuberculin skin test reactivity in the Pakaanóva Indians, in Amazonia, Brazil, after revaccination of all study participants with bacille Calmette-Guerin (BCG). METHODS: The investigation was designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data included PPD readings, age, sex, nutritional status, place of residence, previous tuberculosis, physical examinations and BCG status. Bivariate and multivariate logistic regression analyses were conducted. RESULTS: About 90% (n = 505) of the total population participated. One third (32.1%) of the subjects presented induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation with age; differences between sexes were not observed. Skin reaction was not associated with nutritional status. Individuals with a history of tuberculosis were six times more likely to test positive. History of tuberculosis, age, and previous BCG vaccination were significantly associated with PPD reactivity in the multivariate analyses. CONCLUSION: The Pakaanóva showed a high proportion (58.4%) of non-reactors, even with a recent BCG booster. Sex differences in PPD reactivity were either not present or could not be demonstrated. The association between age and PPD reactivity resembles that observed in other Amazonian populations. The authors discuss the potential of PPD testing as a screening tool to enhance tuberculosis detection, especially in indigenous populations in Amazonia with limited access to health services.

Adolescent↗

[Demographic aspects in indigenous communities of 3 regions of Colombia].

OBJECTIVE: To obtain demographic indicators for some indigenous communities in Colombia situated in three different regions of the country: the Caribbean, the Amazonian basin and the Andes. MATERIAL AND METHODS: Demographic variables gathered in a KAP (knowledge, attitude and practices) survey among the indigenous population in 1993 and 1994 were analyzed. The survey included 11,522 Indian. RESULTS: 45% of the population is under age 15; overall rate of fertility is 6.5 children per woman, and death rate in 1990 was 63.3 children per 1,000 live births. Life expectancy at birth was 57.8 years for women and 55.4 years for men. CONCLUSIONS: The indicators differ substantially from the national figures. Although the indigenous population seems to be undergoing a process of demographic transition, there are marked differences between regions, with significantly higher fertility and infant mortality rates for the Caribbean region.

Adolescent↗

[Infection by hepatitis virus among the indigenous populations of South America: a review of the problem].

After the report of the epidemic outbreak of delta hepatitis among the Yukpa amerindians in the early 80s, the viral hepatitis arose as an important health problem in all the Amerindian communities from the north of South America and the Amazonian Basin. Despite the few data available, the results obtained in different communities from Venezuela (Yukpa, Barí, Yanomami) have shown a high endemicity of hepatitis B and D virus infections and a significant prevalence of hepatitis E virus-specific antibody among their members. By contrast, the infection by hepatitis C virus, which is present in all the urban areas from South America, seems uncommon, or even absent among some Amerindian populations. At the moment, a satisfactory explanation for this findings has not yet been arised. However, it could be possible that the margination of these populations regarding the health care system has been keeping them free of an infection largely linked worldwide to iatrogeny. Vaccination of Amerindian populations against hepatitis B should be taken as a priority of the health care programs. Moreover, such programs should consider the iatrogenic transmission of the HCV as a matter of concern regarding such populations, since parenterally transmitted hepatitis viruses seems to spread quickly among their members once they are introduced, giving rise to serious health problems.

Adult↗

Postmarital residence and within-sex genetic diversity among the Urubu-Ka'apor Indians, Brazilian Amazon.

The analysis of biologic variation in prehistoric human populations separately by sex has been used as a tool to recover post-marital residential rules. These studies, which focus on the sexual distribution of skeletal traits, assume that the degree of intragroup or intergroup biologic diversity is higher in one sex with regard to unilocality (uxori- or virilocality). Despite a recent attempt to interpret this phenomenon in terms of population genetics (Konigsberg 1988), the main assumption has never been tested in situations in which the real residential practice of an indigenous population is known and in which genetic rather than phenotypic data are available. We investigated the within-group and between-group genetic variability among males and females from 4 villages of an uxorilocal Amazonian tribe, the Urubu-Ka'apor, on the basis of 20 polymorphic loci. The results were only partly concordant with the expected. Individual mean per locus heterozygosities were not different between the sexes, and the analysis of genetic heterogeneity showed similar gene frequencies for males and females in all villages. On the other hand, the intergroup approach detected a level of variation significantly greater among females than among males. The ethnographic evidence shows that three of the four subgroups studied belong to the same gamic unity, with the fourth subgroup belonging to another gamic network. Within-sex differences in intergroup analysis turned out to be more evident; yet, when those 3 villages were investigated separately, the female FST (0.0609) proved to be significantly higher than the male FST (0.0218). Such results suggest that the intergroup analysis is more sensitive to the genetic effects of differential migration rates between the sexes. In prehistoric contexts, therefore, an intergroup genetic approach can provide more reliable grounds for sociocultural inferences.

Brazil↗

Amazonia 1492: pristine forest or cultural parkland?

Archaeology and indigenous history of Native Amazonian peoples in the Upper Xingu region of Brazil reveal unexpectedly complex regional settlement patterns and large-scale transformations of local landscapes over the past millennium. Mapping and excavation of archaeological structures document pronounced human-induced alteration of the forest cover, particularly in relation to large, dense late-prehistoric settlements (circa 1200 to 1600 A.D.). The findings contribute to debates on human carrying capacity, population size and settlement patterns, anthropogenic impacts on the environment, and the importance of indigenous knowledge, as well as contributing to the pride of place of the native peoples in this part of the Amazon.

Agriculture↗

Amazonian ethnobotany and the search for new drugs.

Tropical rain forests offer enormous prospects for the discovery of new drugs for use in Western medicine. The Amazon supports 80,000 species of higher plants and a diverse Indian population. Focusing attention on those plants used as medicines by indigenous peoples is the most efficient way of identifying the plants that contain bioactive compounds. There is an urgent need for more ethnobotanists and ethnopharmacologists to be trained to document as much information as possible before it and the plants are lost through destruction of the rain forest and acculturation of the indigenous peoples. Ethnobotanical studies have identified plants documented by early travellers; these include Paullinia yoco and Ilex guayusa which are used as stimulants and have been shown to be rich in caffeine. Studies of the hallucinogen prepared from Banisterioposis caapi have shown that the native people know which plants to add to the mixture to lengthen and intensify the intoxication produced by the beta-carboline alkaloids in the plant. Three major snuffs are used in the Amazonia; the plants from which they are derived have been identified. One of the snuffs also has antifungal and curare-like activities; chemical analysis on the active principles has not been done. Several plants are considered as prime candidates for scientific study as sources of useful chemicals for medicine or industry. These include some used to prepare teas or other infusions for treatment of various symptoms of senile dementia.

Medicine, Traditional↗

Antibodies to HTLV-III/LAV among aboriginal Amazonian Indians in Venezuela.

Serum samples from 224 aboriginal Amazonian Indians were tested for antibodies to HTLV-III/LAV by an indirect immunofluorescence (IF) assay. 9 individuals (4%), 5 of them female, were seropositive by IF and by confirmatory western blotting and radioimmunoprecipitation tests. 3 of the positive sera were collected in 1968. HTLV-III/LAV seropositivity rates varied among the ethnic groups and ranged from 13.3% among the Pemon Indians to 3.3% among the Yanoama tribe. The titres of HTLV-III/LAV antibodies ranged from 1/40 to 1/320. All individuals tested were apparently healthy at the time of the study. None of 211 randomly chosen, healthy blood donors from Venezuelan cities had antibodies to HTLV-III/LAV. The prevalence of specific antibodies among Amazonian Indians suggests the HTLV-III/LAV or a closely related cross-reactive virus may be endemic in this area. The findings also indicate that this virus is indigenous in non-negroid Latin American and negroid tropical populations.

Antibodies, Viral↗

Does traditional medicine use hamper efforts at tuberculosis control in urban Peru?

Decades of social and political unrest have contributed to the urbanization of the population of Peru with large-scale migration from rural Andean and Amazonian communities to overcrowded shantytowns around Lima. We administered a face-to-face survey questionnaire to 116 patients with suspected and proven tuberculosis (TB) in northern Lima to determine the extent to which the use of traditional therapies from indigenous regions persists and the impact of any such use on TB control. Sixty-three percent of participants reported some form of self-treatment prior to presentation to the National Tuberculosis Program; 52% of them used traditional remedies. Symptom duration was longer among self-remedy users than non-users (median = 25 versus 15 days; P = 0.07) and among those exclusively using western remedies rather than traditional remedies (median = 30 versus 15 days; P = 0.01). We thus found no evidence that use of traditional remedies has an appreciable effect on diagnostic delay in Lima.

Adult↗

Risk factors for HTLV-II infection in Peruvian men who have sex with men.

Human T-cell lymphotropic virus type-II (HTLV-II) infection is endemic in indigenous groups in the Americas and injection drug users (IDUs) worldwide. In Peru, HTLV-II infection was previously identified in two indigenous Amazonians. We examined risk factors for HTLV-II infection in 2,703 Peruvian men who have sex with men (MSM): 35 (1.3%) were HTLV-II positive. HTLV-II infection was associated with syphilis, HSV-2 infection, unprotected receptive anal intercourse, and older age. This is the first report of HTLV-II in a non-indigenous non-IDU population in Peru. Additional studies are needed to determine if HTLV-II is a sexually transmitted infection in this and other sexually active populations.

Adolescent↗

Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil: a review.

An historical review is given of American visceral leishmaniasis (AVL), with particular reference to the eco-epidemiology of the disease in Brazil. Following the first records of AVL in this country, in 1934, the sandfly Lutzomyia longipalpis (Lutz and Neiva, 1912) was incriminated as the principal vector. It is now generally accepted, however, that there exist a number of cryptic species under the name of Lu. longipalpis s.l. and that variations in the quantity of the vasodilatory peptide maxadilan in the saliva of flies from different populations of Lu. longipalpis s.l., may account for the variable clinical manifestations of AVL seen in different geographic regions. Distribution of AVL has been shown to extend throughout most of South and Central America, with the domestic dog serving as the principal reservoir of infection for man. However, while one hypothesis suggests that the causative parasite is Leishmania infantum, imported from Europe with the Portuguese and Spanish colonists, the demonstration of a high rate of benign, inapparent infection in foxes in Amazonian Brazil raised an opposing suggestion that the parasite is indigenous to the Americas. Recent reports of similar infections in native marsupials, and possibly rodents, tend to support this view, particularly as Lu. longipalpis is primordially a silvatic sandfly. Although effective control measures in foci of the disease will diminish the number of canine and human infections, the presence of such an enzootic in a variety of native animals will render the total eradication of AVL unlikely.

Animals↗

Primate population densities in three nutrient-poor amazonian terra firme forests of south-eastern Colombia.

We censused primate populations at three non-hunted 'terra firme' forests of south-eastern Colombian Amazonia. The aggregate biomass densities of diurnal primates at all sites were amongst the lowest recorded for any non-hunted forest in western Amazonia and elsewhere in the Neotropics. Densities of red howler monkeys were low, as is typical in Amazonian terra firme forests far removed from white-water rivers, and densities of woolly monkeys were 1.5-3.5 times lower than those estimated for this species in central-western Brazilian Amazonia. Densities of small to mid-sized primates except for brown capuchins (Cebus apella) and white-faced capuchins (Cebus albifrons) were similar to those of other oligotrophic Amazonian forest sites. Our results are in agreement with other studies showing that terra firme forests of lowland Amazonia typically sustain a low biomass density of primates and other mid-sized to large vertebrates. Large reserves are therefore required to assure the viability of primate populations in oligotrophic systems. Given the escalating negative impacts of human habitat disturbance and hunting in Colombian Amazonia, we urge that a baseline sampling protocol to quantify the abundance and distribution of the harvest-sensitive vertebrate fauna be established within protected areas and the large indigenous reserves so that conservation efforts can be defined and implemented.

Animals↗