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The seroprevalence of Helicobacter pylori among secluded Indian populations of South America was determined to gain insight into the evolutionary history and possible transmission patterns of the organism. Serum samples obtained from 1024 donors in 22 different villages were tested by enzyme-linked immunosorbent assay for immunoglobulin G antibodies, and the results were confirmed by Western blot. The overall seroprevalence was 92%: >80% of children tested positive by 3 years of age, the highest prevalence in populations studied to date. Comparison of H. pylori prevalence with that of herpes simplex virus type 1, which is known to be transmitted orally, demonstrated a linear correlation in their prevalence rates, suggesting that these pathogens share risk factors. However, H. pylori seroprevalence was consistently higher, indicating that additional routes of transmission exist and/or that the organism is more transmissible. Seroprevalence did not correlate with the length of contact with the outside world. These results suggest that H. pylori was indigenous to the South American Indians and was not introduced by contact with outsiders.

There have been reports of nonrandom mating (negative-assortative mating) or preference for individuals of different major histocompatibility complex (MHC) genotypes in both mice and humans. We have examined the association of HLA-A and HLA-B genotypes, both for each locus by itself and for two-locus genotypes, in mates of 194 couples from 11 South Amerindian tribes. The proportion of couples sampled averaged >50% of the total matings with progeny for 10 of the tribes. In nearly all cases, HLA-sharing proportions were very close to those expected from random mating, suggesting strong negative-assortative mating for MHC is not present in these South Amerindians.

Two KM alleles occur in 1075 South Amerinds of 14 tribes in approximately balanced and uniform frequency. However, the number of heterozygotes is 12.7% greater than expected by frequency analysis and 16.5% greater by segregation analysis. This excess is evident in children 0-4 years of age and may reflect either prenatal or early childhood selection. The frequencies of GM haplotypes were different, and quite uniformly so, in diverse tribes. Most GM heterozygotes can only be distinguished from GM 1,2,17 21 homozygotes by DNA or family relationship. No deficit of GM homozygotes was observed in 119 children in whom heterozygosis was determined by family. Thus, the KM polymorphism, like HLA, may be maintained by preferential survival of heterozygotes, but GM probably depends on another mechanism.

We have examined HLA-A and HLA-B in a large sample of families of South Amerindians for non-random mating and for Mendelian segregation in their progeny. The proportion of couples sampled for mating averaged over 50% of the total matings with progeny for 10 of the 11 tribes with 10 or more known matings. In nearly all cases, HLA-sharing proportions were very close to those expected from random mating, suggesting strong negative-assortative mating for MHC is not present in these South Amerindians. In progeny from these matings and others in 23 tribes, there was a large deficiency of homozygotes (excess of heterozygotes) compared with Mendelian expectations. In particular, there was a deficiency in all types of matings except when the female was a homozygote and the male shared one allele with her; the reciprocal mating showed no such deficiency. This non-reciprocity suggests the importance of some type of maternal-fetal interaction. A model to describe these results showed very surprising properties for two alleles: no change in allelic frequency like neutrality, an excess of heterozygotes like heterozygote advantage, and a minimum fitness at intermediate allelic frequency like heterozygote disadvantage. For three or more alleles, the model has the qualities of a traditional balancing selection model.

A longitudinal study, spanning 25 years and great demographic and cultural change, found a persistently high prevalence of human T-lymphotropic virus type II (HTLV-II) in the Xikrin Kayapo Indians of Brazil. More than 10% of the children continue to develop immune reactions to the virus in infancy, a sharp increase in seroprevalence occurs between ages 15 and 30 years, and prevalence in older woman still approaches 100%. This suggests that the major modes of transmission (breast milk and sexual activity) have not changed. The demonstration of stable maintenance of HTLV-II in one ethnic group makes migration theories of its dispersal more plausible. However, the infection may not be a negligible burden on population survival: at least 1 of 62 persons followed until age 40 years died of possible tropical spastic paraparesis (TSP).

Long terminal repeat (LTR)-based restriction fragment length polymorphism (RFLP) analysis of human T cell lymphotropic virus type II (HTLV-II) from 17 seropositive Kayapo Indians from Brazil showed that all 17 samples contained a unique HTLV-IIa subtype (A-II). Additional RFLP screening demonstrated the presence of this subtype in two of three Brazilian blood donors and a Mexican prostitute and her child. In contrast, 129 samples from blood donors and intravenous drug users (IDUs) from the United States, two Pueblo Indian samples, five samples from Norwegian IDUs, and two samples from blood donors from Denmark were all found to be a different HTLV-IIa subtype (A-III). Phylogenetic analysis of two Kayapo and one Mexican LTR sequences showed that they cluster with a subtype A-II sequence from a Brazilian blood donor and with sequences from two prostitutes from Ghana and Cameroon. These results demonstrate that infection with the A-II subtype is endemic among the Kayapo Amerindians, has disseminated to non-Indian populations in Brazil, and is also present in Mexico. Furthermore, the A-II subtype does not appear to represent an origin for the HTLV-IIa infection in urban areas of the United States and Europe. This study provides evidence that HTLV-IIa may be a Paleo-Indian subtype as previously suggested for HTLV-IIb.

Class I HLA antigens have been compared in 5,835 Melanesians of Papua New Guinea and 2,028 Amerindians of South America. The sample includes 50 PNGMel ethnolinguistic groups and 22 SAmInd groups. Both carry 15 serologically defined antigens and an undefined C allele. Except for A2 in Papua New Guinea and Cw1 in South America, these antigens are widely distributed in their respective populations. Nine (A2 and A24, B39, B60 and B62, and Cw1, Cw3, Cw4, and Cw7) are common to both. This commonality suggests that these two populations derive from an ancestral population with less polymorphism than modern East Asians. In both populations several theoretically possible haplotypes were absent, and other haplotypes were in positive disequilibrium in both. The parallels in disequilibria suggest that haplotypes are subject to selective forces acting on the level of allelic interaction. Based on three locus haplotype frequencies, the PNGMel groups form five clusters with internally typical linguistic and geographic characteristics and miscellaneous category, but SAmInd groups show no cluster.

Isolated South Amerinds, a population at very high risk from infectious disease, mount good immune responses to pneumococcal polysaccharides, viral antigens and other immunogens. No unusual immunoglobulin allotype or HLA antigen, which might explain the high risk from infectious disease, was found among them. Responses are examined in relation to the immunogenetic markers that are most prevalent. Amerinds with Gm 1,2,17,21 responded less well than persons without this haplotype to 10 of 12 pneumococcal polysaccharides, and those who were homozygous at the HLA class I loci responded less well to viral antigens. However, these differences are not strong and there are few such findings relative to the number of possibilities examined. The most distinctive immunogenetic characteristic of these populations is their low level of polymorphism at all tested loci. Their susceptibility to infectious agents can be attributed to this genetic uniformity and a consequent ability of pathogens to adapt to the population.

Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararaô Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararaô. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararaô and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west.

Serological studies on 926 blood samples from 703 Brazilian Kayapo (Cayapo) Indians showed, by conventional definition of HTLV seropositivity, a 28% prevalence of human T lymphotropic virus (HTLV) infection, the highest yet reported. Immunoblot (WB) and SYNTH-EIA patterns indicate that the predominant infecting agent is type II. Of children under 15 years old, 12% were positive, and of persons over 60, more than 60%. Perinatal and heterosexual modes of transmission offer an adequate explanation of this incidence. Infection in infancy may include infection via breast milk from women other than the mother. Evidence of new infection in adults is apparent at an earlier age in women than in men. This pattern of antibody prevalence was not determined by cohort effects, as demonstrated by tests of serial specimens. Enzyme immunosorbent assay (EIA) absorbencies were not stable in the paired specimens: five serum pairs reverted and mean absorbencies declined over some age ranges. Many specimens with relatively high, but less than positive, EIA results were positive by immunoblot (WB). This suggests that the standard EIA end point does not identify all infected persons. If the WB alone indicates positivity, 47% of the whole population, and more than 80% of the older age groups, are infected with HTLV-II.

Previous attempts to classify South American Indian tribes according to genetic characteristics have failed to yield a hierarchical system of relationships. This can be explained by the facts that (1) tribal populations did not evolve through sequential fissions but through frequent fusions of groups with diverse histories and (2) allele frequencies have been held at nearly common values by intertribal migration or balancing selection. A valid model must allow for fusion and mixed populations as well as for fission; factor analysis or newer methods of fuzzy mathematics permit this. The effects of migration and balancing can be made more manageable by partitioning them according to the limited time periods recorded by haplotypes. An initial attempt using factor analysis and HLA haplotype data on 19 rain forest tribes revealed two overlapping clusters that are largely but not neatly separated by the lower Amazon River. Several tribes, especially in the west, were excluded from these clusters.

Three Amerindian populations, two from Rondônia, Brazil (Karitiana and Rondônia Suruí), and one from Campeche, Mexico (Mayan), were typed for up to 30 nuclear restriction fragment length polymorphisms (RFLPs). Heterozygosities, both observed and expected, were compared with those of Europeans. Average heterozygosity is reduced among these Amerindians (relative to that of Europeans) by 7.0% (Mayan) to 27.1% (Karitiana). This amount of heterozygosity in the nuclear DNA is nevertheless high enough that it is unlikely that there was a severe or prolonged bottleneck.

Data on 31 genetic systems were obtained for 421 individuals belonging to the Arara, Araweté, Mundurucu, and Jamamadi tribes of northern Brazil. The Jamamadi depart farthest, and the Mundurucu least, from South American Indian averages. These data are analyzed together with those of 24 other Amazonian groups. Genetic distances and corresponding dendrograms indicate a cluster of 14 related tribes living north of the Amazon river. These genetic results show only a modest correlation with linguistic and geographic relationships among these groups.

Allele frequencies for the orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), alpha-2-HS-glycoprotein (AHSG) and complement component I (IF) loci were studied in 393 individuals of three Brazilian Indian tribes. In the ORM1 locus only two alleles were observed among the Urubu-Kaapor, while five were found among the Pacaás Novos. The frequency of ORM1*1 was similar in these two tribes (0.734 and 0.715, respectively) but departed more markedly among the Parakanã (0.870). Variation for ORM2 locus was found among the Pacaás Novos only, with ORM2*3 being observed in just three individuals. A new variant (AHSG*PN) was found in the AHSG system. Frequency for AHSG*1 was unexpectedly low in the three tribes, especially, among the Pacaás Novos, where the prevalence (0.145) is the lowest considering other data reported thus far. For IF locus, variability was also restricted to only one trible (Urubu-Kaapor) and attributed to a new polymorphic allele, IF* A3.

The number of persons with homozygous HLA haplotypes in several groups of South American Indians was 39% less than that expected assuming unmodified equilibrium. In a subpopulation of 122 persons whose parents' HLA constitutions were known, there were 56% fewer homozygous persons than expected. This deficit was widely distributed in different haplotypes and different tribal groups.

Serologic tests for hepatitis B prevalence and immunogenetic characterizations were carried out on a sample of 800 persons from several isolated tribes of the lower Amazon basin and the southern Andes. The prevalence of hepatitis B antigen carriers and of antibody to the surface antigen varied from one tribe to another, but were high in all the forest tribes. The serologic evidence indicated high infection rates early in life, but also an increasing proportion showing evidence of infection with increasing age. The frequency of past infections was not differentially associated with the antigen status of the mother or father. A higher proportion of infected males than females had antigenemia. Contrary to published reports, no association of antigenemia was found with any HLA-A, B or C antigen or immunoglobulin allotype, individually or interactively. Antibody prevalence, however, did differ in persons with different HLA haplotypes.

Incidence of various infectious diseases in several Amazon Indian tribes has been determined serologically. Diseases that infect only man fall into two distinct categories. Those which can persist in an individual for a prolonged period are highly endemic, but those which are infectious only in the acute phase die out quickly after introduction. The suggestion is made that the latter diseases could not perpetuate themselves before the advent of advanced cultures and did not exert selective pressures on the human genetic constitution until relatively recently.

Serologic surveys for treponemal disease were carried out in 1970-1976 among three linguistically distinct and isolated population groups in the Brazilian Amazon Region and among the Mapuche Indians of southern Chile. Three patterns were found: 1) no evidence for treponemal infection in two very recently contacted groups; 2) sporadic positive individuals in groups with long periods of contact with non-Indian populations; and 3) a high prevalence of positive tests in one cultural group with limited exposure to non-Indians. The seroepidemiology and clinical manifestations of a possible treponemal infection in those villages with a high prevalence of positive tests were unlike those of the classically described human treponematoses.

Among 166 children whose parents share the HLA-A, -B, and -C antigens of at least one haplotype, there is a superficial concordance between observed and expected proportions of children whose mothers would recognize no foreign antigen in them. However, this balance is composed of fewer (64%) homozygous offspring than expected and more (147%) than the expected number of genotypes identical to the mother's. A homozygous child would be expected to recognize his or her mother as foreign, unless the mother was also homozygous, but an HLA-identical child would not. Thus, the number of children who might be immunologically tolerant of their mothers was greater than expected. No one of the three loci included in designating haplotypes was individually responsible for the divergences in haplotype frequency.

Results concerning HLA types and 22 other blood genetic systems are reported for the Parakanã Indians of northern Brazil, a tribe that is notable for the light color and pilosity of some of its members. No clear evidence of Caucasoid admixture was found, but the Parakanã show unusual frequencies in the EsD1, PGM1(1) Gc2, CpB, Fya, Dia, and LM genetic markers. In addition, the very rare Rh allele ry is present, as well as what seems to be a new PGM2 variant. There is very limited heterogeneity in the HLA system. All these distinctive features may have arisen through a combination of founder effects and genetic drift. However, low FIS values, as well as higher mean ages in heterozygous as compared to homozygous persons, suggest that an heterotic effect is counteracting these dispersive forces.

Antibody to hepatitis A in an Amerindian tribe was found in everyone over 50 years old but in no one younger. We suggest that the tribe had become infected with hepatitis A virus during the period, about 50 years earlier, when they engaged in raids on Luso-Brasilian settlers, that the virus failed to persist in the tribe when they withdrew into isolation, and that those who had been infected maintained antibody titers without boosting since that time.

New HLA data for the Tirio, Parakanã, Kayapo and Mapuche tribes, as well as supplementary data for the Waiãpi, are presented. Taken together with previously published information on South American Indians, these typings show a remarkably homogeneous gene pool with a restricted range of polymorphisms and a further restricted set of haplotypes.

HLA B-C haplotypes exhibit common disequilibria in populations drawn from four continents, indicating that they are subject to broadly active selective forces. However, the A-B and A-C associations we have examined show no consistent disequilibrium pattern, leaving open the possibility that these disequilibria are due to descent from common progenitors. By examining HLA haplotype distributions, I have explored the implications that would follow from the hypothesis that biological selection played no role in determining A-C disequilibria in 10 diverse tribes of the lower Amazon Basin. Certain haplotypes are in strong positive disequilibria across a broad geographic area, suggesting that members of diverse tribes descend from common ancestors. On the basis of the extent of diffusion of the components of these haplotypes, one can estimate that the progenitors lived less than 6,000 years ago. One widely encountered lineage entered the area within the last 1,200 years. When haplotype frequencies are used in genetic distance measurements, they give a pattern of relationships very similar to that obtained by conventional chord measurements based on several genetic markers; but more than that, when individual haplotype disequilibria in the several tribes are compared, multiple origins of a single tribe are discernible and relationships are revealed that correlate more closely to geographic and linguistic patterns than do the genetic distance measurements.

Vaccine induced measles antibody titers in the Upper Xingu Indians remained at satisfactory levels without evidence of decline over a period of six years without re-exposure. However, in another area, a vaccination program which used a reduced dose of vaccine was only 63% effective. When measles virus was introduced to the latter area a protracted epidemic ensued with 23% of the population becoming ill and six deaths. The deaths occurred exclusively under 13 months or over 40 years of age.

The situation of unacculturated Brazilian Amazon tribes is described. The isolation of these populations has been sufficiently tight that they have been free of most epidemic diseases of the cosmopolitan world, although diseases associated with persistent infection have a high prevalence. The history of measles epidemics in Amerind populations is reviewed and it is concluded that most deaths can be prevented by basic nursing care but that there is a residual excess mortality characteristic of these populations. Three Brazilian virgin-soil populations and one experienced tribe in Chile, the Mapuche, were vaccinated against measles. Elevated febrile responses were observed in the three virgin-soil populations relative to the fevers seen in the Mapuche and in cosmopolitan populations. Nutritional status, immunological experience, humoral immune response and genetic characters have been examined for an explanation of this phenomenon. The most pronounced correspondence detected so far is a high degree of homozygosity in HLA loci of the virgin populations.

A total of 136 individuals were studied in relation to 31 genetic systems, and the results were compared with South American Indian averages and previous surveys on the Wayana of French Guiana and Surinam. The information was afterwards integrated with data from other Carib groups, and two types of genetic distances (Nei's and Edwards') were calculated a) between five groups, considering ten systems; and b) between nine groups, using five systems. The two measures of genetic distances correlated well (Spearman's correlation coefficient around 0.70), and there was good agreement between the geographical and genetic distances. All analyses indicated a peripheral position for the Apalai-Wayana and their distinctiveness from the Wayana of French Guiana and Surinam, suggesting that intertribal fusions may play an important role in the genetic differentiation of these populations.

Data on blood group, serum protein, erythrocyte enzyme, and histocompatibility antigen (HLA) traits are presented for the Waiãpi, a Tupi-speaking tribe of the Brazilian and French Guianas. Intra- and intertribal comparisons have been made between these data, and previously published data from French Guiana, from another Tupi tribe and from other tribes of neighboring areas, and from the continent as a whole. For this purpose, we have modified the usual measure of genetic distance to obtain a value which is independent of the number of loci being considered. The intertribal genetic distances do not correlate with linguistic affinity. Social differences, which may have affected the rate of drift from the continental mean, correlate better with genetic distances.

Measles in an unvaccinated virgin population exacted a death toll of 4.2% which fell particularly hard on the age groups which would ordinarily be protected by maternal antibody. The organ system most affected was quite variable. When the virus spread to a largely vaccinated village it caused only one death. Herd immunity seemed to protect many who were not vaccinated. Vaccine failed to protect 7.7% of the recipients. Some of these failures may have been due to erroneous record, vaccination in the presence of maternal antibody or inactivated vaccine, but most occurred in a few family groups related by genetics and similar past immunological experience.