Comparative seroepidemiology of HTLV-I and HTLV-III in the French West Indies and some African countries.

The prevalence of antibodies detected by ELISA against human T-lymphotropic viruses, type I (HTLV-I) and type III (HTLV-III-LAV), is described in a comparative serosurvey in the French West Indies and African countries. The data confirm that the Caribbean basin is endemic for HTLV-I. In this region, HTLV-I antibody prevalence varied from 3.4% to 5.2% among blood donors and increased with age to reach a value of 33% among elderly people from the Dominica Island. In French Guyana, a South American country bordering the Caribbean sea, differences in antibody distribution across three ethnic groups (black Bonis, Indian Wayanas, and Hmongs from Asia) provide clues for investigation of the mode of HTLV-I transmission. Africa appears to be an endemic continent for HTLV-I and HTLV-III. For both viruses, the antibody prevalence exhibited an increasing gradient from northern to equatorial through Sudanic areas. These preliminary data by showing that Africa represents an endemic reservoir of HTLVs and, possibly, of other human retroviruses should stimulate further investigations on the natural history and the geographical origin of these viruses.

Mutations in the coding region of c-myc occur independently of mutations in the regulatory regions and are predominantly associated with myc/Ig translocation.

Constitutive expression of c-myc resulting from a chromosomal translocation, which juxtaposes c-myc to an immunoglobulin gene, is a pivotal lesion in Burkitt's lymphomas. This deregulated expression of c-myc is associated with mutations in the regulatory regions, i.e. the first exon and the first intron of c-myc in tumors where the chromosomal breakpoint is not itself within the regulatory region. Until recently it was widely believed that the c-myc protein in these tumors is wild type. We have demonstrated that in a fraction of Burkitt's lymphomas from Africa and from the continental USA, and in mouse plasmacytomas, the c-myc gene carries mutations in the coding region. We now show that, occasionally, such mutations are also present in multiple myelomas--tumors which do not carry translocations or amplifications of c-myc. We also show that the frequency of the c-myc coding region mutations in BL is independent of the frequency of mutations in the regulatory region. These results suggest that the mechanisms that induce missense mutations involving the coding region of c-myc may be different from those that lead to mutations in the regulatory regions.

Diabetes is not caused by cassava toxicity. A study in a Tanzanian community.

OBJECTIVE: To test the hypothesis that consumption of cassava with liberation of cyanide causes diabetes in malnourished individuals. RESEARCH DESIGN AND METHODS: Glucose tolerance was assessed in two rural communities in Tanzania; in one (Nyambori), the main source of calories was cassava; and in the other (Uswaa), cassava was rarely eaten. Undernutrition was prevalent in both communities. The people of Nyambori were known to have high dietary cyanide exposure for many years from consumption of insufficiently processed cassava. Of the 1435 people in Nyambori greater than or equal to 15 yr old, 1067 (74%) were surveyed, and 1429 of 1472 (97%) eligible subjects in Uswaa were surveyed. All had 75-g oral glucose tolerance tests and measurement of BMI. Plasma and urine thiocyanate and blood cyanide also were measured in some subjects. RESULTS: Mean +/- SD plasma and urine thiocyanate levels in Nyambori were 296 +/- 190 and 497 +/- 457 microM (n = 204), respectively, compared with 30 +/- 37 and 9 +/- 13 microM, respectively, in Uswaa (n = 92) (P less than 0.001 for all differences). The mean blood cyanide level in Nyambori was elevated (1.4 [range 0.1-30.2] microM; n = 91). The prevalence of diabetes in the cassava village (Nyambori) was 0.5% compared with 0.9% in Uswaa (NS). The prevalence of IGT was similar in the two villages in the 15- to 34- and the 34- to 54-yr-old age-groups; but in those greater than or equal to 55 yr old, IGT was higher in Nyambori (17.4 vs 7.2%, P = 0.029). Mean fasting and 2-h blood glucose levels were slightly higher in Nyambori village after adjusting for age, sex, and BMI (4.5 vs. 4.2 and 5.0 vs. 4.4 mM, respectively). CONCLUSIONS: High dietary cyanide exposure was not found to have had a significant effect on the prevalence of diabetes in an undernourished population in Tanzania. Cassava consumption is thus highly unlikely to be a major etiological factor in so-called MRDM, at least in East Africa.

Sexual behaviour survey in a rural area of northwest Tanzania.

OBJECTIVE: Little is known about variations in patterns of sexual behaviour in different countries, cultures, and subpopulations that determine the spread of HIV-1. Quantitative studies are required to improve understanding. METHODS: To assess reported patterns of sexual behaviour, we administered a standardized questionnaire to 416 men and 498 women aged 15-49 years from a rural population in northwest Tanzania. RESULTS: Reported levels of sexual activity were highest in men and among younger age groups. The number of sexual partners and number of sex acts per unit of time were strongly correlated: men reported 10 times as many lifetime partners than women. Frequency of sexual partner exchange plateaued earlier in women (by age 25 years) than in men (by age 35 years). For the great majority, age of first intercourse was 15 years or younger; older subjects were older at first intercourse and had fewer lifetime partners than younger subjects. CONCLUSIONS: This age-related pattern suggests that more recent birth cohorts have behaviour patterns that increase the risk of sexually transmitted infectious agents such as HIV. Preventive education programmes should be targeted at young adults, who adopt higher risk profiles of frequent partner exchange linked with first intercourse at an early age.

Population-based study of HIV-1 infection in 4,086 subjects in northwest Tanzania.

A population-based HIV-1 seroprevalence survey of 4,086 individuals, aged 15-49 years, in the North Mara district of Tanzania from rural, periurban, and urban areas, including high-risk (prostitutes, and co-workers) individuals, was performed in 1989 and 1990. The overall seroprevalence was 7.3% (95% confidence interval, 6.5-8.1), with a gradient of seropositivity from high-risk 13.0% (9.1, 16.8), urban 8.8% (7.6, 10.0), periurban 6.5% (4.7, 8.4), to rural 2.6% (1.6, 3.7) subjects. Adjusted for population group, HIV-1 seroprevalence was significantly elevated for men over age 24 and for women 20-34 years old, while age-specific prevalence rates were similar for men and women in the rural area. Recent treponemal infection, measured by the rapid plasma reagin test, was not associated with HIV-1 seropositivity in men or women. These data suggest a growing HIV-1 epidemic paralleling rising rates in other rural areas of Africa distant from areas that have been previously recognized as having high prevalence.

HLA antigens in East African Black patients with Burkitt's lymphoma or nasopharyngeal carcinoma and in controls: a pilot study.

A pilot study is reported of HLA-A, B, and C antigens in 141 East African Blacks comprising patients with Burkitt's lymphoma or nasopharyngeal carcinoma, either with active disease or in long-term remission, together with comparable controls. This study forms part of a wider program investigating host factors in these diseases. A protocol was selected for optimal testing of cells processed and cryopreserved between 1972 and 1976, largely under field conditions, which employed a two-color fluorochromasia typing procedure. Antigen distribution and computed haplotype frequencies in the total unrelated population are given. New findings include an approximately equal frequency of Aw23 and Aw24, a high (18%) incidence of Bw21, and the gametic associations of Aw36 with Bw44, and Aw30 with Bw45. Of the major group of B15-related antigens reported earlier. SV is the most common, and there are strong linkages of SV with Cw2 and Bu with Cw3. The possible presence of further variants at the A- and B-loci is reported. The proportion of B-locus antigen "blanks" in this study is 5.9%. Relationships have been sought between the HLA antigens and diseases studied: the antigen A29, possibly in linkage with Bw42, shows a correlation with disease susceptibility, and associations are suggested between Bw44 (in possible combination with Aw36) and resistance to both BL and NPC, and between Bw45 and long-term remission in NPC.

Multisample probe for fast-atom bombardment / mass spectrometry.

An inexpensive multisample fast-atom bombardment (FAB) probe assembly was designed for high-throughput analysis of samples on a VG ZAB-SE mass spectrometer. The system consists of a vacuum lock system and a FAB probe whose tip contains five or more sample wells. The probe enters the mass spectrometer source region perpendicular to the secondary ion beam axis, The probe is maintained at high voltage on contact with a spring clip attached to the screen plate of the source block. Sample throughput with the multisample probe is twice that of a coaxial probe, with about twice the sensitivity and no sample cross contamination.

Seroprevalence of hepatitis C virus in the general population of northwest Tanzania.

Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.

Lymphocyte enzyme activities in East African blacks: decrease in 5'nucleotidase and possible relation to immunosuppression.

Microanalysis of subcellular organelle marker enzymes was applied to cryopreserved lymphocytes (obtained and processed in the field) from East African blacks with moderate to severe malnutrition and subject to locally endemic parasitic and infectious diseases. An initial study demonstrated that activities of these enzymes, with the partial exception of catalase, were stable to cryopreservation. Cryopreserved and thawed lymphocyte specimens (1 to 3 X 10(6) viable cells) from 26 Africans and 20 Caucasian controls were studied. There was a highly significant decrease in 5'nucleotidase activity in these African subjects. Activity of another plasma membrane enzyme, gamma-glutamyl transferase, and of marker enzymes for other intracellular organelles, was not significantly different between the two groups, indicating that the nucleotidase alteration is highly specific. 5'Nucleotidase activity in a group of 17 East African blacks of high socio-economic status lay between the values obtained in the other two groups and was not significantly different from either. Further studies on 5'nucleotidase showed no evidence that the enzyme is functionally different in Africans. The differences in activity of this enzyme in Africans may reflect the known immuno-suppressive effects of infectious disease and malnutrition or may have a genetic basis which may in turn be associated with the pathogenesis of secondary immunodeficiency.

Determination of T-lymphocyte subsets on site in rural Tanzania: results in HIV-1 infected and non-infected individuals.

With the FACSCount flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168 subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part of a population-based serosurvey and AIDS education programme; 134 other subjects were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV-1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1 seronegative subjects from the local population were 980 CD4 cells (95% CI 930, 1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive subjects from the local population had significantly lower CD4 cell counts, higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower and CD8 cells significantly higher in HIV-1 seropositive hospital patients compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital patients had CD4 counts lower than 600. These results establish baseline values for the lymphocyte subsets in this population and indicate that this technique can be used in remote areas to monitor progress of HIV-infected individuals.

The frequency of Epstein-Barr virus infection and Burkitt's lymphoma at high and low altitudes in East Africa.

Burkitt's lymphomas (BL) is frequent in the tropical lowland of Africa but rare--even in the tropics--at altitudes higher than 5,000 feet above sea level. Serological surveys were carried out in Uganda and Tanzania to see whether the variation in BL incidence from high to low areas is paralleled by a variation in the extent of infection with the putative Epstein-Barr virus. Sera were collected from samples of the general child population living at high and low altitudes in the West Nile District in Uganda and in North Mara, Tanzania. All sera from these surveys were tested for anti-EBV antibodies to Viral Capsid Antigens (VCA) and to Early Antigens (EA) at the International Agency for Research on Cancer in Lyon, France. The results showed that both the prevalence and the strength of positive EBV (VCA and EA) titres are nearly similar in the lowlands and on the high plateux in East Africa. This lack of association between BL incidence and extent of EBV infection fails to support the notion of a causal role between the virus and the tumor, but does not totally exclude this possibility since some other environmental factor which is essential for BL development, may have a geographical distribution that parallels that of BL.

Oral yeast flora of a population in an area of Tanzania bordering an AIDS endemic zone.

Mouth swabs from 1,288 individuals in the North Mara region of Tanzania were cultured for yeasts. Subjects were randomly selected from rural and urban areas, and a group of food handlers were also studied. Yeasts were cultured from 407 (31.6%) and Candida albicans from 141 (10.9%) subjects. A wide variety of other yeast species were also identified.

PIP: Between May-October 1989, health personnel took mouth swabs from 875 15-55 year old male and female adults from rural Luo Imbo division of Tarime district, 145 similar individuals from the town of Tarime, and 268 food handlers from Tarime and other neighboring towns in the North Mara region of Tanzania to determine the prevalence of oral yeast flora in areas near an AIDS endemic zone. Laboratory personnel at the Shirati Hospital in Shirati isolated yeasts in 31.6% of the cases with most cases having Candida albicans (10.9%) followed by Saccharomyces cerevisiae (7.4%) and Trichosporon capitatum (6.5%). They were able to identify at least 23 other yeasts among the study group. Food handlers had the highest carriage rate (36.4%) then rural dwellers (32.5%) and urban dwellers (24.8%). C. albicans was present more often in the food handlers (17.5%) than either the rural or urban dwellers (9.5%) and 6.9% respectively). Thus the researchers suggested that the already occurring medical surveillance activities of food handlers should also monitor Candida infection. S. cerevisiae (used in food and drink fermentation processes) was also more prevalent in food handlers (10.8%) than the other 2 groups (6.3% and 7.6% respectively). On the other hand, laboratory staff isolated T. capitatum more often from rural dwellers (8.6%) than urban dwellers (2.1%) and food handlers (2.6%). In a study in Zaire, S. cerevisiae was the predominant oral yeast in AIDS patients. 9 (0.7%) subjects had T. beigelii, 1 of whom carried HIV-1. which has been associated with invasive infections in immunocompromised patients. Ongoing seroepidemiological studies in Tanzania are looking at any associations between subclinical C. albicans and other yeast infections, HIV-1 infection, and the development of AIDS.

Dense, viscous brine behavior in heterogeneous porous medium systems.

The behavior of dense, viscous calcium bromide brine solutions used to remediate systems contaminated with dense nonaqueous phase liquids (DNAPLs) is considered in laboratory and field porous medium systems. The density and viscosity of brine solutions are experimentally investigated and functional forms fit over a wide range of mass fractions. A density of 1.7 times, and a corresponding viscosity of 6.3 times, that of water is obtained at a calcium bromide mass fraction of 0.53. A three-dimensional laboratory cell is used to investigate the establishment, persistence, and rate of removal of a stratified dense brine layer in a controlled system. Results from a field-scale experiment performed at the Dover National Test Site are used to investigate the ability to establish and maintain a dense brine layer as a component of a DNAPL recovery strategy, and to recover the brine at sufficiently high mass fractions to support the economical reuse of the brine. The results of both laboratory and field experiments show that a dense brine layer can be established, maintained, and recovered to a significant extent. Regions of unstable density profiles are shown to develop and persist in the field-scale experiment, which we attribute to regions of low hydraulic conductivity. The saturated-unsaturated, variable-density groundwater flow simulation code SUTRA is modified to describe the system of interest, and used to compare simulations to experimental observations and to investigate certain unobserved aspects of these complex systems. The model results show that the standard model formulation is not appropriate for capturing the behavior of sharp density gradients observed during the dense brine experiments.

Bioremediation of chemical spills.

It is evident from the data collected to date that substantial progress was made in the remediation of the site prior to the shutdown of the bioreclamation system. Extrapolation of the data suggests that completion of the project was imminent. Further remediation at the site, including the possibility of expanding the original area treated with in situ bioreclamation, is pending further definition of the new sources of contamination. The success of the two projects described here demonstrates the efficacy and potential of enhanced bioreclamation in remediating contamination problems both in soils and in groundwater.

Space-time clustering of Burkitt's lymphoma in East Africa: analysis of recent data and a new look at old data.

Forty cases of Burkitts' lymphoma (BL) in North Mara, Tanzania, with onset between 1971 and 1977, were analysed for evidence of space-time clustering. Previous analyses in East Africa had produced conflicting results. The Knox method used in those analyses dichotomizes the space and time scales and does not take into account the degree of closeness. The Mantel method, a generalization of Knox's, does permit closeness between pairs of cases to enter into computations. To see whether this method could clarify matters, previously reported data sets from West Nile, Uganda and North Mara were reanalysed. Unexplained differences were found between West Nile and North Mara with respect to age, sex and temporal distributions of BL, and between the eastern and western parts of North Mara with respect to incidence. In West Nile between 1961 and 1965, there was clustering. All of the Mantel analyses and a few of the Knox analyses were highly significant (p less than 0.0025). Since 1966, evidence of clustering is weak. In North Mara, there was no statistical evidence of space-time clustering between 1971 and 1977, as there was none between 1964 and 1970. The conflicting results in East Africa are compatible with a model involving several factors which "move about", or with a single factor which is sporadic in some areas but constant in others. Alternatively, artifactual biases or coincidence may have created or wiped out the appearance of clustering. Results of space-time clustering analyses permit little discrimination between infectious and non-infectious etiologic hypotheses. Either one type or both may be operating.

Effect of a malaria suppression program on the incidence of African Burkitt's lymphoma.

From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.

Serial studies on the evolution of drug resistance in malaria in an area of east Africa: findings from 1979 up to 1986.

Observations, previously reported for 1979-82, have been continued up to 1986 on the development of drug resistance in P. falciparum in the North Mara area of Tanzania, where a chloroquine chemosuppression campaign was attempted from 1977 to 1982. The WHO micro in-vitro test for chloroquine and other drugs was used. Because of the large number of tests done, each test was characterized by the mean minimum inhibitory concentrations (MIC) of drug needed to prevent schizont development instead of counting the numbers of schizonts. The MIC for chloroquine has risen progressively each year but changes in the findings of in-vivo tests were less dramatic possibly due to the effects of immunity. Resistance to amodiaquine has followed that to chloroquine at a lower level, and in the last years the MIC for quinine has risen. Sporadic resistance to mefloquine was found and, by in-vivo test, to sulphadoxine-pyrimethamine. Possible factors in the evolution of drug resistance are discussed together with implications for the future.

Serial studies on the evolution of chloroquine resistance in an area of East Africa receiving intermittent malaria chemosuppression.

Serial in vitro and in vivo tests for chloroquine sensitivity of Plasmodium falciparum were carried out from 1979 to 1982 in an area of E. Africa where chemosuppression with chloroquine had been attempted since 1977. Within 1(1/2) years there were signs of a decreasing drug response. Chloroquine resistance was first detected in 1981 and this increased markedly in 1982. Other contributory causes for the rise of parasite rates in children were possibly a decline in the efficiency of the drug distribution system and also immunological factors. Evidence of resistance to pyrimethamine was also found. Observations were made of the heterogeneity of the parasites' responses with emerging resistance. Implications for the future are discussed.

Konzo, an epidemic upper motor neuron disease studied in Tanzania.

An epidemic of spastic paraparesis was studied in a drought-affected rural area of Tarime district in northern Tanzania. The uniform clinical findings in 39 cases, aged 4-46 yrs, indicated abrupt symmetric isolated and permanent but not progressive damage to the upper motor neurons. Due to the failure of other food crops, the diet at onset consisted almost exclusively of bitter cassava roots, a drought-tolerant starchy root crop widely cultivated in Africa. The drought increased the natural occurrence of cyanogenic glucosides in the cassava roots, and the processing procedure normally applied in order to remove cyanide before consumption was shortened because of food shortage. The resulting high dietary cyanide exposure was confirmed by very high serum levels of thiocyanate, the detoxification product of cyanide. Tests for HTLV-1 antibodies were negative and no other findings supported an infectious aetiology. The clinical findings and the associations with cassava toxicity are almost identical to those reported from outbreaks of spastic paraparesis in Mozambique and in Zaire, where this disease was first reported under the name 'konzo'. We thus conclude that konzo constitutes a distinct upper motor neuron disease entity, probably caused by a toxic effect from insufficiently processed cassava under adverse dietary circumstances.