Non-malarial infectious diseases of antenatal care in pregnant women in Franceville, Gabon.

BACKGROUND: In sub-tropical countries, infectious diseases remain one of the main causes of mortality. Because of their lack of active immunity, pregnant women and their unborn children represent the most susceptible people. In Gabon, data on infectious diseases of pregnant women such as syphilis and rubella are either scarce or very old. Few studies have assessed T. gondii infection during pregnancy in the country. Here, we evaluate seroprevalence of HIV, HTVL-1, syphilis and T. gondii and rubella infection during antenatal care among women living in Franceville, Gabon. METHODS: A retrospective study was conducted on data collected from May 2007 to July 2010. After signing an informed written consent form, all pregnant women consulting in two hospitals of Franceville (Gabon) and in offices of maternity and childbirth health centers were included. Demographic and clinical data were collected. Serum samples were collected and analysed using immunological assays relevant for HIV (Genscreen HIV-1 version 2, Bio-Rad®, Marne la Roquette, France).HTLV-1 (Vironostika HTLV-1, Biomérieux®, Marcy l'Etoile, France), T. pallidum (TPHA/VDRL), BIOLABO®SA), rubella virus (Vidas Biomerieux®, Marcy l'Etoile, France) and T. gondii (Vidas Biomerieux®, Marcy l'Etoile, France) diagnoses were performed. Data analysis was done using the Stat view 5.0 software. RESULTS: A total of 973 pregnant women were assessed. The mean age was 25.84 ± 6.9 years, with a minimum age of 14.0 years and a maximum of 45.0 years. Women from 26 to 45 years old and unemployed women were the most prevalent: 41.93% and 77.18%, respectively. The prevalence of studied infectious diseases were 2.50% for syphilis, 2.88% for HTLV-1, 4.00% for HIV with no significant difference between them (p = 0.1). Seropositivity against rubella was higher (87.56%, n = 852) than seropositivity against T. gondii (57.35%, n = 557), (p < 0.0001). Only 5 (0.51%) co-infection cases were found: 2 co-infected with HIVand T. pallidum, 2 co-infected with HIV and HTLV-1, and one co-infected with T. pallidum and HTLV-1. Sixty-two pregnant women were seronegative against toxoplasmosis and rubella (6.37%). CONCLUSION: High levels of seropositivity against T. gondii and the rubella virus were observed. The prevalence of T. pallidum and HTLV-1 were lowest but HIV prevalence in young women was worrying.

Pro- and anti-inflammatory cytokines in children with malaria in Franceville, Gabon.

Severe Plasmodium falciparum malaria anemia (SMA) is a major cause of mortality in pediatric wards. Variations in inflammatory mediator production play an essential role in disease outcomes. Indeed, several studies have shown the involvement of pro- and anti-inflammatory cytokines such as IFN-γ, IL-6, TNF-α and IL-10 in malaria immunopathology. In other hand the exact role of Th17 cytokines such as IL-17, IL-22 and IL-21 in malaria remains poorly documented. Here, we investigated IFN-γ, TNF-α, IL-6, IL-12, IL-10, IL-4, IL-13, IL-17, IL-22 and IL-21 circulating levels and their association with malaria anemia and parasitemia in Gabonese children. Levels of IFN-γ (500 ± 100.2 pg/ml), IL-6 (64 ± 14.2 pg/ml), IL-10 (505 ± 35 pg/ml), IL-13 (30.6 ± 5.6 pg/ml) were significantly higher (P < 0.03) in infected children than in uninfected controls (210 ± 20 pg/ml, 17.5 pg/ml, 50 ± 25.9, pg/ml, 17.48 pg/ml, respectively). IFN-γ levels were significantly lower (P = 0.04) in children with SMA (400 ± 200 pg/ml) than in those with uncomplicated malaria (900 ± 450 pg/ml) and higher in those with parasitemia (P = 0.019). Levels of IL-6 and IL-10 were significantly higher in children with malarial anemia (P < 0.001) and hyperparasitemia (P < 0.0001). A significant association between IL-10 levels and parasite density was observed (P < 0.00001). IL-22 levels were significantly higher (P = 0.01) in infected children (72.57 ± 7.5 pg/ml) than in the controls (54.96 ± 1.93 pg/ml). IL-21 levels (44.46 ± 17.27 pg/ml) decreased with the severity of anemia (P < 0.05), whereas IL-17 levels increased in children with SMA (12.25 ± 1.25 pg/ml) than in those with mild malaria anemia (MMA: 6.2 ± 5.25 pg/ml, P = 0.002). Data suggest possible role of IFN-γ in the protection against SMA and parasite clearance. However, IL-6 and IL-10 could play a role in inflammatory response and pathophysiology of severe malaria anemia. Also, the role of IL-22 and IL-17 in P. falciparum malaria infection should be investigated.

High Level of Specific Anti-Plasmodium Falciparum Merozoite IgG1 Antibodies in Rural Asymptomatic Individuals of Dienga, South-Eastern Gabon.

Plasmodium falciparum merozoite antigens (PfMAgs) play an essential role in the development of immunity to malaria. Currently, P. falciparum: protein 113 (Pf 113), apical membrane antigen 1 (AMA1), erythrocyte binding antigens (EBA175), and reticulocyte binding protein homologue 5 (RH5) are among the most PfMAgs studied. A comparative analysis of naturally acquired antibodies against these antigens in children would increase our knowledge about the development of protective immunity. Analysis of antibodies to Pf113, PfAMA1, PfEBA175, and PfRH5 was conducted in rural population during 2013 and 2014. Both prevalence and levels of total IgG anti-PfAMA1 were higher than that of IgG anti-PfEBA175, anti-PfRH5, and anti-Pf113. Seroconversion to PfAMA1 and PfEBA175 occurred moderately in young children and reached to the maximum in adolescent and in adults. High prevalence of IgG anti-Pf113 was observed in young children of 3 to 6 years old in 2013. The four antigens were recognized by IgG 1, 2, 3, and 4 antibodies from a large proportion of the subjects, and all of them induced high levels of specific IgG1 against PfAMA1, PfEBA175, fewer by Pf113 and PfRH5. Many asymptomatic children had specific IgG1 recognizing multiple antigens, and these IgG1 antibodies could be associated with a reduced risk of developing malaria symptoms.

Comparative Antibody Responses Against three Antimalarial Vaccine Candidate Antigens from Urban and Rural Exposed Individuals in Gabon.

The analysis of immune responses in diverse malaria endemic regions provides more information to understand the host's immune response to Plasmodium falciparum. Several plasmodial antigens have been reported as targets of human immunity. PfAMA1 is one of most studied vaccine candidates; PfRH5 and Pf113 are new promising vaccine candidates. The aim of this study was to evaluate humoral response against these three antigens among children of Lastourville (rural area) and Franceville (urban area). Malaria was diagnosed using rapid diagnosis tests. Plasma samples were tested against these antigens by enzyme-linked immunosorbent assay (ELISA). We found that malaria prevalence was five times higher in the rural area than in the urban area (p < 0.0001). The anti-PfAMA1 and PfRh5 response levels were significantly higher in Lastourville than in Franceville (p < 0.0001; p = 0.005). The anti-AMA1 response was higher than the anti-Pf113 response, which in turn was higher than the anti-PfRh5 response in both sites. Anti-PfAMA1 levels were significantly higher in infected children than those in uninfected children (p = 0.001) in Franceville. Anti-Pf113 and anti-PfRh5 antibody levels were lowest in children presenting severe malarial anemia. These three antigens are targets of immunity in Gabon. Further studies on the role of Pf113 in antimalarial protection against severe anemia are needed.

Prevalence of malaria, prevention measures, and main clinical features in febrile children admitted to the Franceville Regional Hospital, Gabon.

Recently, major progress has been made in controlling malaria in Africa. However, in Gabon, little information is available on the role of malaria in childhood febrile syndromes, the use and efficacy of preventive measures, and Plasmodium species distribution. Here, we characterized malaria in febrile children in Franceville, Gabon through a cross-sectional study at the pediatric unit of the Franceville Regional Hospital. We registered 940 febrile children. Their general condition was markedly altered in 11.7% of cases (n = 89/760); among them 19 (21.4%) had a severely altered condition. Malaria was the second most frequent etiology (22.0%; n = 162/738), after respiratory tract infections (37.3%; n = 275/738). Children with malaria (63 ± 39 months) were older than children without malaria (40 ± 37 months) (p = 0.0013). Hemoglobin, red blood cell, white blood cell, and platelet values were lower in children with malaria than in those without malaria (p < 0.0001). Anemia was the most common feature of severe malaria (70.6%; n = 12/17), followed by neurological involvement (23.5%; n = 4/17). The prevalence of malaria was significantly higher in children older than 60 months than in younger children (40% vs. 15.5%; p < 0.0001). Plasmodium falciparum accounted for 97.5% of cases (158/162), followed by Plasmodium malariae (2.5%; n = 4/162). Bed net use was high (74.4%; n = 697/936) and contributed to malaria prevention (p = 0.001). Good basic knowledge of malaria also had a preventive effect (p < 0.0001). The prevalence of malaria in children in Franceville did not decrease significantly from 2009 to 2012, remaining at about 20%, highlighting that preventive measures should be reinforced.

Marked Rise in the Prevalence of Asymptomatic Plasmodium falciparum Infection in Rural Gabon.

Control strategies implemented a decade ago led to a marked reduction in the prevalence of malaria in many countries. In Dienga, southeastern Gabon, the prevalence of microscopic P. falciparum infection was 7% in 2003, close to the pre-elimination threshold of 5%. The aim of this work was to determine the prevalence of P. falciparum infection in the same community a decade later. A cohort of 370 individuals aged from 3 to 85 years living in Dienga was investigated for P. falciparum infection; during six passages (P) in 15-month period. Demographic data were collected, along with behaviors and attitudes towards malaria. Plasmodium infection was diagnosed by microscopy (ME), followed by PCR to detect submicroscopic infection. The prevalence of P. falciparum infection in P1, P2, P3, P4, P5 and P6 was respectively 43.5% (25.1% ME+, 18.4% PCR+); 40.9% (27.0% ME+, 13.9% PCR+), 52.7% (26.1% ME+, 26.6% PCR+); 34.1% (14.1% ME+, 20% PCR+), 57.7% (25.4.% ME+, 32.3% PCR+); and 46.2% (21.4% ME+, 24.8% PCR+) with an overall average of 45.9% (95%CI [37.0-54.7], 23.2% ME+ and 22.7% PCR+). P4 and P5 prevalences were statically different throughout the six passages. Microscopic prevalence was significantly higher than that observed ten years ago (23% [n = 370] vs 7% [n = 323], p < 0.001). Asymptomatic infections were the most frequent (96%). Gametocytes were detected in levels ranging from 5.9% to 13.9%. Insecticide-treated nets, indoor residual insecticides, and self-medication were used by respectively 33.2% (95%CI [29.0-37.4]), 17.7% (95%CI [15.5-19.9]) and 12.1% (95%CI [10.6-13.6]) of the study population. A near-threefold increase in P. falciparum infection has been observed in a rural area of southeastern Gabon during a 10-year period. Most infections were asymptomatic, but these subjects likely represent a parasite reservoir. These findings call for urgent reinforcement of preventive measures.