Human genetic factors related to susceptibility to mild malaria in Gabon.

Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF-alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum.

Impairment of natural killer cell activity in Chlamydia trachomatis infected individuals.

Natural killer (NK) cell activity is impaired in Chlamydia trachomatis-infected patients. The mechanisms behind the altered NK functions are not clear, but data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. To investigate whether this impairment is related to a defect at the target cell binding and/or the postbinding level, we evaluated highly purified NK cells obtained from 125 C. trachomatis-infected patients and compared them with 101 normal controls for their ability to kill K-562 and U-937 cell lines using a 51Cr release assay; release tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma); and kill anti-IgM preincubated P-815 cell line (ADCC activity). We found a decrease in the lytic capability of NK cells from C. trachomatis-infected patients against target cell lines; decreased ability to kill bound target cells; and low levels of released TNF-alpha and INF-gamma after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell reaction during chlamydial infection is related to defects both at the target and postbinding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 support the hypothesis of an anergic process during chlamydial infection.

Leptospirosis and Ebola virus infection in five gold-panning villages in northeastern Gabon.

An exhaustive epidemiologic and serologic survey was carried out in five gold-panning villages situated in northeastern Gabon to estimate the degree of exposure of to leptospirosis and Ebola virus. The seroprevalence was 15.7% for leptospirosis and 10.2% for Ebola virus. Sixty years after the last seroepidemiologic survey of leptospirosis in Gabon, this study demonstrates the persistence of this infection among the endemic population and the need to consider it as a potential cause of hemorrhagic fever in Gabon. There was no significant statistical correlation between the serologic status of populations exposed to both infectious agents, indicating the lack of common risk factors for these diseases.

Ebola hemorrhagic fever outbreaks in Gabon, 1994-1997: epidemiologic and health control issues.

From the end of 1994 to the beginning of 1995, 49 patients with hemorrhagic symptoms were hospitalized in the Makokou General Hospital in northeastern Gabon. Yellow fever (YF) virus was first diagnosed in serum by use of polymerase chain reaction followed by blotting, and a vaccination campaign was immediately instituted. The epidemic, known as the fall 1994 epidemic, ended 6 weeks later. However, some aspects of this epidemic were atypical of YF infection, so a retrospective check for other etiologic agents was undertaken. Ebola (EBO) virus was found to be present concomitantly with YF virus in the epidemic. Two other epidemics (spring and fall 1996) occurred in the same province. GP and L genes of EBO virus isolates from all three epidemics were partially sequenced, which showed a difference of <0.1% in the base pairs. Sequencing also showed that all isolates were very similar to subtype Zaire EBO virus isolates from the Democratic Republic of the Congo.

Plasmodium coatneyi: differential clinical and immune responses of two populations of Macaca fascicularis from different origins.

Two species of macaques, including two Macaca fascicularis from the Philippines, two M. fascicularis from Mauritius, and one Macaca mulatta, were experimentally infected with blood stages of Plasmodium coatneyi and followed during their clinical, parasitological, biological, and immunological evolution. Plasma cytokine (TNF-alpha, IL-1beta, IL-6, IFN-gamma) production peaked for all monkeys 11 days after inoculation, concomitantly with peaks of parasitemia. Only the M. fascicularis from the Philippines survived the infection. The main features, which discriminated nonfatal from fatal cases, were the observation in M. fascicularis from the Philippines of a mean CD4+/CD8+ ratio below I and of their ability, as revealed by mitogenic stimulation of whole blood, to produce increasing amounts of IFN-gamma as infection evolved. The contribution of environmental and genetic factors, which may differentiate the three groups of monkeys and therefore explain fatal or nonfatal evolution of the infection among them, is discussed.

Factors influencing resistance to reinfection with Plasmodium falciparum.

A treatment-reinfection study design was used to investigate the relationships between host immunologic and/or genetic factors and resistance to reinfection with Plasmodium falciparum. Sixty-one children in Gabon were enrolled in a cross-sectional study to measure the prevalence of each human plasmodial species. All were given amodiaquine for radical cure of parasites, and 40 were subsequently followed-up for 30 weeks. Successive blood smears were examined to measure the delay of reappearance in blood of asexual stages of P. falciparum parasites. Presence of infection during the cross-sectional survey was associated with male sex, non-deficient glucose-6-phosphate dehydrogenase activity, plasma interleukin-10 level, and anti-LSA-Rep antibody concentration. Resistance to reinfection was related to the presence of anti-LSA-J antibodies, and the absence of anti-LSA-Rep antibodies. Moreover, P. malariae-infected subjects were usually co-infected with P. falciparum, and were also more rapidly reinfected with P. falciparum after treatment, compared with those without P. malariae infection.

[Serological investigation of toxoplasmosis in patients of the M.I.P. center of Franceville (Gabon)]. / Enquête sérologique sur la toxoplasmose chez les consultantes du centre de P.M.I. de Franceville (Gabon).

The seroprevalence of toxoplasmosis was assessed between 1995 and 1997 on 767 pregnant women on the occasion of their medical check-ups for pregnancy in the preventive health centre of Franceville, province of the Haut-Ogooué, Gabon. Among the women under investigation, 71.2% were found to be IgG seropositive, including 2.6% IgM seropositive. When compared to similar studies conducted for the last 20 years in the same region, these results give evidence of an increase of the seroprevalence to toxoplasmosis among pregnant women, contributing to a decreased risk of contracting the disease during pregnancy.

Seroprevalence of four sexually transmitted diseases in a semi-urban population of Gabon.

Using the cluster-sampling method, the authors estimated the seroprevalence of 4 sexually transmitted diseases (STDs) among the sexually active general population in a city of 30,000 inhabitants in the east of Gabon. The seroprevalences were 2% for HIV-1, 13.8% for hepatitis B, 8.6% for Treponema pallidum and 59.6% for Chlamydia trachomatis. The seroprevalences of hepatitis B and chlamydia were stable over time and similar to those registered in other countries of central Africa. On the other hand, the seroprevalence of T. pallidum is notably low in comparison with these countries and seems to be decreasing. The seroprevalence of HIV-1 is also low but has doubled in 8 years in the city. Immigrant women from west Africa were a high-risk group for STDs but more generally, cohabiting was a risk factor for women.

PIP: Findings are presented from a seroprevalence survey of HIV, hepatitis B, syphilis, and chlamydia conducted in Franceville, Gabon, during 2 days in January 1996, in a representative sample of the sexually active general population aged 14-55 years. 456 usable sera were collected from 457 individuals recruited in 20 clusters of 25 people each. Franceville is a city of approximately 30,000 inhabitants. 2% were infected with HIV-1, 13.8% with hepatitis B, 8.6% with Treponema pallidum, and 59.6% with Chlamydia trachomatis. The seroprevalences of hepatitis B and chlamydia were stable over time and similar to those reported in other central African countries. However, the seroprevalence of T. pallidum is quite low relative to those other countries and appears to be decreasing. The seroprevalence of HIV-1 is also low, but twice the level observed in 1988.