Patricia Tortevoye

Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population.

BACKGROUND Transmission of human herpesvirus 8 (HHV-8), the aetiological agent of Kaposis sarcoma, is known to occur during sex among homosexual men. However, other modes of HHV-8 transmission remain to be elucidated in endemic populations. METHODS We did a population-based seroepidemiological survey in a village in French Guiana among 1337 individuals of African origin (age 2-91 years) who had reliable genealogical data. Plasma samples were taken and tested for HHV-specific IgG by immunofluorescence assay. Risk factors and familial correlations for HHV-8 seropositivity were modelled by logistic regression analysis by use of the estimating equations approach, which expresses familial dependences in terms of odds ratios. Familial odds ratios were also acquired by use of the distribution of all possible pairs of a given familial dependence. FINDINGS The overall HHV-8 seroprevalence was 13.2% with no difference according to sex. HHV-8 seropositivity was strongly age dependent: at 1.2% under 5 years, HHV-8 seroprevalence rose up to a plateau around 15% between 15 and 40 years, and showed a seroprevalence of more than 27% in individuals older than 40 years. Strong familial aggregation in HHV-8 seroprevalence was found with high mother-child (odd ratio 2.8 [95% CI 1.6-5.0]) and sib-sib (3.8 [1.6-9.5]) correlations. By contrast, no significant correlation between spouses (0.6 [0.2-1.9]) was seen. INTERPRETATION This pattern of familial aggregation, together with the variation of HHV-8 seroprevalence with age, indicate that, in endemic populations, HHV-8 transmission mainly occurs from mother to child and between siblings during childhood and adolescence.

Meta-Analysis on the Use of Zidovudine and Interferon-Alfa in Adult T-Cell Leukemia/Lymphoma Showing Improved Survival in the Leukemic Subtypes

PURPOSE Human T-cell lymphotropic virus type-I-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-α) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined. PATIENTS AND METHODS We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed. RESULTS According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first-line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021). CONCLUSION These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL.

Mother‐to‐child transmission of human T‐cell‐leukemia/lymphoma virus type I: Implication of high antiviral antibody titer and high proviral load in carrier mothers

In order to gain new insights into the risk factors influencing human‐T‐cell‐leukemia/lymphoma‐virus‐type‐I (HTLV‐I) mother‐to‐child transmission, a retrospective study of HTLV‐I infection among children born to HTLV‐I‐seropositive women was carried out in a highly HTLV‐I‐endemic population of African origin living in French Guyana. The study covered 81 HTLV‐I‐seropositive mothers and their 216 children aged between 18 months old and 12 years old. All plasma samples were tested for the presence of HTLV‐I antibodies by ELISA, immunofluorescence assay and Western blot. HTLV‐I provirus was detected, in the DNA extracted from peripheral‐blood mononuclear cells, by polymerase chain reaction (PCR) using primers specific for 3 different HTLV‐I genomic regions (LTR, gag and pX) and quantified by a competitive PCR assay. Out of the 216 children, 21 were found to be HTLV‐I‐seropositive, giving a crude HTLV‐I transmission rate of 9.7%, while among the 180 breast‐fed children 10.6% were HTLV‐I‐seropositive. Perfect concordance between serological and PCR results was observed, and none of the 195 HTLV‐I‐negative children was found HTLV‐I‐positive by PCR. In conditional (by family) logistic‐regression models, HTLV‐I seropositivity in children was associated with an elevated maternal anti‐HTLV‐I‐antibody titer (OR 2.2, p = 0.0013), a high maternal HTLV‐I proviral load (OR 2.6, p = 0.033) and childs gender, girls being more frequently HTLV‐I‐infected than boys: OR 3.6, p = 0.0077 in the model including maternal anti‐HTLV‐I‐antibody titer and OR 4.1, p = 0.002 in the model including the maternal HTLV‐I proviral load. Int. J. Cancer 82:832–836, 1999.

Simian Foamy Virus Transmission from Apes to Humans, Rural Cameroon

Bites from apes efficiently transmit the foamy virus to humans in natural settings in central Africa.

Respective Roles of Serological Status and Blood Specific Antihuman Herpesvirus 8 Antibody Levels in Human Herpesvirus 8 Intrafamilial Transmission in a Highly Endemic Area

Transmission of human herpesvirus 8 (HHV-8), the etiological agent of Kaposi’s sarcoma, occurs mainly during childhood in endemic countries and, to a large extent, through intrafamilial contacts. To additionally investigate this familial transmission, and especially the role of plasma anti-HHV–8 antibody titers, we conducted a large survey in a village from Cameroon, Central Africa, including 92 families (608 individuals). Plasma samples were tested for specific IgG directed against HHV-8 lytic antigens by immunofluorescence assay, and titers were determined by 2-fold dilutions. Global HHV-8 seroprevalence was 60%, raising from 32% under 9 years up to a plateau of around 62% between 15 and 40 years. The familial correlation patterns in HHV-8 seropositive/seronegative status showed strong dependence from mother to child and between siblings. In contrast, no familial correlation in anti-HHV–8 antibody levels was observed among infected subjects. In particular, no relationship was observed between the anti-HHV–8 antibody titer of HHV-8 seropositive mothers and the proportion of their HHV-8 seropositive children. Furthermore, a random permutation study of the anti-HHV–8 antibody titers among HHV-8 infected subjects showed that the main risk factor for infection was the HHV-8 serologic status and not the antibody level. In addition, no correlation was found between anti-HHV–8 antibody levels and buffy coat HHV-8 viral loads in a subsample of 95 infected subjects. Overall, these results strongly suggest that, in this highly endemic population from Central Africa, HHV-8 transmission mainly occurs from mother to child and between siblings, and it is independent of plasma antibody levels of HHV-8 infected relatives.

Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings

Merkel cell polyomavirus (MCPyV) is thought to be the etiological agent of Merkel cell carcinoma, but little is known about its distribution and modes of transmission. We conducted seroepidemiological surveys in more than 1000 individuals, from two populations from Cameroon. Overall MCPyV seroprevalence was high in both populations (>75% in adults). Data from the first population, comprising mainly children, indicated that MCPyV infections mostly occurred during early childhood, after the disappearance of specific maternal antibodies. Results from the second family-based population provided evidence for familial aggregation of MCPyV infection status. We observed significant sib-sib correlation (odds ratio=3.42 [95% CI 1.27-9.19], p=0.014), particularly for siblings close together in age, and a trend for mother-child correlation (OR=2.71 [0.86-8.44], p=0.08). Overall, our results suggest that MCPyV infection is acquired through close contact, possibly involving saliva and/or the skin, especially between young siblings and between mothers and their children.

Demographic and familial characteristics of HTLV-I infection among an isolated, highly endemic population of African origin in French Guiana†

To determine the epidemiological characteristics of human T cell leukemia/lymphoma virus type I (HTLV‐I) infection in the endemic village of Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91 years (mean age 21) were studied from November 1994 through April 1995. Plasma samples were screened by an HTLV‐I ELISA and an IFA test (on MT2 cells), and positive samples were tested by an HTLV‐I and ‐II type‐specific Western blot. Overall seropositivity in the village was 6.7%, but HTLV‐I infection was restricted to 3 of 6 ethnic groups, including the Noir‐Marron (descendants of escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir Marron/other ethnicity (3.6%). In the Noir‐Marron population of 1,222 persons, including 606 men and 616 women and representing 76% of those tested, HTLV‐I seroprevalence increased significantly with age in both sexes, reaching 40% in women older than 50 years. Univariate risk factors for HTLV‐I seropositivity in women included older age, more pregnancies, more live births and a history of hospitalization. A cross‐sectional analysis of sexual partners demonstrated an excess of discordant female HTLV‐I+/male HTLV‐I− couples, indicating preferential male‐to‐female sexual transmission. The demonstration of 11 HTLV‐I‐seropositive children aged less than 15 years, of whom 9 had a seropositive mother, suggested maternal–child HTLV‐I transmission. Our results demonstrate a very high seroprevalence of HTLV‐I in this South American population descended from African slaves, probably due to high rates of mother‐to‐child and sexual transmission within this rather isolated group. Int. J. Cancer 76:331–336, 1998.© 1998 Wiley‐Liss, Inc.

Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.

Evidence for a Recessive Major Gene Predisposing to Human Herpesvirus 8 (HHV-8) Infection in a Population in Which HHV-8 Is Endemic

Infection by human herpesvirus 8 (HHV-8), as measured by the presence of specific antibodies, was shown in countries in which HHV-8 infection is endemic to exhibit familial aggregation and a peculiar variation with age (rapid increase until puberty followed by a plateau in young adults). To investigate whether host genetic factors could explain these findings, a segregation analysis was performed of 81 families of African origin (1623 subjects; HHV-8 seroprevalence, 11.9%) living in a village in French Guiana in which HHV-8 infection is endemic. Results provide evidence for a recessive gene controlling susceptibility or resistance to HHV-8 infection. This gene is predicted to have a major effect during childhood, with almost all homozygous predisposed subjects ( approximately 6% of the population) being infected by age 15. For nonpredisposed subjects, HHV-8 infection in childhood strongly depends on virus exposure (through an HHV-8-infected mother), whereas the risk of infection appears to be low in young adults, with no evidence for heterosexual transmission.

Serological and Molecular Evidence That Human Herpesvirus 8 Is Endemic among Amerindians in French Guiana

We evaluated the presence of human herpesvirus 8 (HHV-8) infection among groups of Amerindians in French Guiana. The overall prevalence of antibodies against lytic HHV-8 antigens was 23.0% (180/781), increasing from 18.4% in children <6 years old to approximately 30% in older persons (>45 years). Seroprevalence was higher in Amerindians living in remote localities than it was in those living in the coastal region. Analysis of a 725-base pair fragment of the K1 gene amplified from DNA from a Wayampi Amerindian showed that the virus belonged to molecular subtype E, which has hitherto been found in only a few Amerindians in Brazil and Ecuador.