Infectious diseases in primitive societies.

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.

Endemic transmission of HTLV type II among Kayapo Indians of Brazil.

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.

Twenty-five years of HTLV type II follow-up with a possible case of tropical spastic paraparesis in the Kayapo, a Brazilian Indian tribe.

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).

Endemicity and phylogeny of the human T cell lymphotropic virus type II subtype A from the Kayapo Indians of Brazil: evidence for limited regional dissemination.

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.

The optimal age for vaccination against measles in an Asiatic city, Taipei, Taiwan: reduction of vaccine induced titre by residual transplacental antibody.

Children vaccinated when aged between six and thirteen months against measles in Taipei showed a high frequency of response, similar to that reported from Nairobi, Kenya and contrasting with analogous data for the USA. The age for optimal protection against measles mortality by a single dose of vaccine in this group of children is nine months. Maternal antibody exerted a negative effect on measles antibody titre in vaccinees beyond the age at which it blocked the response so that the infants of mothers with the higher titres themselves had lower titres. A separate effect of immunological immaturity on titre of the response could not be demonstrated in children over six months of age.

Durability of passive measles antibody in Jamaican children.

Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries.

Acute respiratory infections in ambulatory malnourished children: a serological study.

We studied the aetiological agents of acute respiratory infections occurring in an ambulatory population of 83 malnourished Jamaican-born children aged 6 to 32 months using serological methods for diagnosis. In 60% (38/63) of symptomatic children and in 25% (5/20) of those without reported disease the following microorganisms were observed: parainfluenza viruses in 15 children, influenza viruses in 12, adenovirus in 10, respiratory syncitial virus in 7 and Mycoplasma pneumoniae in 7 children. The prevalence of the viral infections apparently increased with the severity of malnutrition.

Comparison of PPVT-R and WISC-R in a mild/moderate handicapped sample.

The Peabody Picture Vocabulary Test-Revised, Form L was compared with the Wechsler Intelligence Scale for Children--Revised with a sample of 32 mild/moderate handicapped students (24 boys, 8 girls). Significant correlations were found between the WISC-R Full Scale IQ (.46) and the WISC-R Verbal IQ (.50) and the PPVT-R, but no significant correlation was found between the WISC-R Performance IQ and the PPVT-R (.34). Mean scores on the PPVT-R and WISC-R were significantly different.

Mother-child HLA compatibility ratios in children of Amerinidian parents who share common haplotypes.

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.

Measles active and passive immunity in a worldwide perspective.

'The simplest of all virus disease is measles' said Kenneth Maxy 40 years ago in a chapter on epidemiology. I hope that the data set out here provide the reader with a sufficiently complete and clear picture of the factors that determine measles epidemiology, that he or she will agree with Maxy's prescient words. Measles is an antigenically complex virus, but few components of the immune response to this virus are epidemiologically relevant. The relevant components are durable for a lifetime. They can be conveniently measured by serological tests, and the results of these tests correlate well with measles immunity. The tests show that measles is an extremely infectious disease, and that very high antibody prevalence rates are needed for herd protection. The currently available measles vaccine is capable of yielding adequate antibody prevalence rates for herd immunity, but to achieve this, immunization procedural flaws and faulty records must be kept to very low levels. The greatest obstacle to worldwide control of measles is a failure of vaccination programs to produce adequate herd immunity levels in less-developed countries. There, vaccine must be given promptly after passive immunity wanes, because the level of endemicity is so high. It is difficult to determine just what age is optimal, because it varies from one country to another. Premature vaccination not only fails to immunize, but also interferes with subsequent re-immunization. Because we now know this, further direct tests of vaccine effectiveness in very young children are ethically undesirable, and methods that use determination of passively acquired antibody are to be preferred. The levels of antibody that mothers have to pass to their children vary considerably. These differences are important in comparisons of South Asian countries with others, but not elsewhere. Differences in efficiency of transport of antibody across the placenta also play a role, but usually a minor one. Most important seems to be variation in antibody durability in the infant. Where families are poor, the children acquire many infections at an early age, and passively acquired antibody is swept out. These children who are least able to withstand the effects of measles infection, are hit at the earliest age. To provide protection for them, the vaccine must be given at a carefully determined age, specific for each community. Only when this is done can we hope to reduce measles worldwide to a sufficiently low level that it will be removed as a threat to persons in the United States, or anywhere else.

Reasons for failure of genetic classifications of South Amerind populations.

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.

Tracing prehistoric migrations by the viruses they carry: human T-cell lymphotropic viruses as markers of ethnic relationships.

Three reasons that HTLV-I and HTLV-II would not be expected to trace human migrations over extended time periods have been examined, and none has proven fatal to the theory. Transmission of the HTLVs (human T-cell lymphotropic viruses) in endemic settings highly depends on passage through breast milk, and this creates a pattern of distribution similar to that of mitochondrial DNA. The HTLVs probably evolve at variable rates, making the extent of sequence change a poor tool for dating human migrations. However, qualitative relationships between the sequence of human population separations and virus strain may be more regular. The uniqueness of viruses as markers of human relationship gives this method special value as a source of novel ideas regarding human movements and as independent confirmation of migration hypotheses that have been based on more conventional methods.

The role of herd immunity in control of measles.

Measles vaccine cannot give high sero-conversion rates in developing countries. The high birth rates characteristic of these countries lead to infection at a very early age, thus making it difficult to vaccinate before exposure to the disease. Nevertheless, if given early in life, the vaccine can reduce the rate of virus circulation and thus raise the age at which children are infected. Once that is done, higher sero-conversion rates can be obtained by raising the age at vaccination. During the period when vaccine is given at an early age, the titers in responding children will be low, and this will leave children of the next generation with little protection. It is important, therefore, that if vaccine is used early the program be intensively and consistently applied to control virus circulation before the next generation is born.

PIP: In densely populated developing countries, it is impossible to protect the majority of the measles-susceptible population regardless of the immunization schedule used. In such countries, a large proportion of measles cases occur early in life and, by the time children have lost maternal antibodies and thus become responsive to vaccine, many will already have become infected. Revaccination at a later age is not a satisfactory solution to the problem of vaccine effectiveness in developing countries, because early vaccination inhibits the effects of a second dose. If effective control of measles is to be achieved in developing countries, a program must be designed to build upon and expand herd immunity. Herd immunity is difficult to establish against measles, because the virus is extremely contagious and a high level of population immunity is required. Population immunity affects the frequency of virus transmission and thus the age at infection. Active immunization makes the most significant contribution to herd protection, but the duration of passive protection from maternal antibodies is variable and important in providing protection during infancy when measles is often fatal. When given early in life, measles vaccine can reduce the rate of virus circulation and raise the age at which children are infected. Once this is achieved, higher seroconversion rates can be obtained by raising the age at vaccination. During the period that vaccine is given at an early age, the titers in responding children will be low leaving the next generation with little protection. Thus, if measles vaccine is administered early, the measles control program should be intensively and consistently applied to control virus circulation before the next generation is born.

Interrelationships between Amerindian tribes of lower Amazonia as manifest by HLA haplotype disequilibria.

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.

Hepatitis A antibody in an isolated Amerindian tribe fifty years after exposure.

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.

Maternally derived measles immunity in era of vaccine-protected mothers.

Measles hemagglutinin-inhibiting and neutralizing antibody titers are lower in women young enough to have been immunized by vaccination than in older women. In the children of both young and older mothers the antibody is concentrated 1.7-fold across the placenta, and the child's initial titer remains proportional to that of its mother. The transferred antibody is diluted by the baby's growth and degraded with a mean half-life of 48 days. By 8 1/2 months of age, 95% of the children of the mothers born since 1963 would have become susceptible to measles and responsive to immunization; the same level of susceptibility is not reached by children of mothers born before 1958 until 11 1/2 months of age. Among the offspring of younger mothers, a small group remains, about 2% of the total, with titers high enough to provide protection for 12 months, and these children would be poorly served if the age for vaccination were reduced for all. However, selective early vaccination of children of young mothers who have low antibody titers would eliminate an important focus of measles susceptibility.