Severe malaria in children and adolescents in Southeast Gabon.

INTRODUCTION: Malaria remains a significant public health problem in sub-Saharan Africa. Child mortality due to severe malaria remains high in developing countries despite improvements in malaria management and a better understanding of its pathophysiology. To address the lack of epidemiological studies on severe malaria in Gabon, this study describes the epidemiological aspects of severe malaria in rural, semi-rural, and urban areas of southeast Gabon. METHODS: Demographic, clinical, and laboratory data for children and adolescents aged 0-18 years were collected in 2019 from hospital records at three health facilities in southeastern Gabon. The patients included in the study were positive for P falciparum malaria diagnosed by microscopy with at least one of the malaria severity criteria. RESULTS: Severe malaria accounted for 18.8% (667/3552) of malaria cases. Children aged 0-5 years accounted for 71.8% (479/667) of all severe malaria cases. Adolescents over 15 years of age were the least affected by severe malaria with 4.2% (28/667). Across the study, severe anemia (49.0%, 327/667), convulsions (43.0%, 287/667), respiratory distress (5.1%, 34/667), and altered consciousness (4.8%, 32/667) were the most frequent clinical signs of severe malaria in children. Franceville was the locality most affected by severe malaria with 49.2% (328/667), followed by Koulamoutou with 42.0% (280/667) and Lastourville with 8.8% (59/667). Convulsions (50.6%, 166/328) and coma (6.1%, 20/328) were more frequent in children living in urban areas. In contrast, severe anemia (56.7%, 186/339) and jaundice (6.8%, 23/339) were more common in children living in semi-rural areas. CONCLUSION: Severe malaria is more prevalent in urban areas in regions with a high malaria transmission intensity. However, in this study, the epidemiological characteristics of severe malaria were similar in the three settings (urban, rural, and semi-rural areas) despite different levels of urbanization. Nevertheless, the various signs of severity were more frequent in Franceville, an urban area. Children under 5 years of age remain the most vulnerable age group.

Epidémiology of malaria from 2019 to 2021 in the southeastern city of Franceville, Gabon.

BACKGROUND: In Gabon, a new national malaria control policy was implemented in 2003. It resulted in a decrease in the number of malaria cases in the country. In March 2020, the disruption of routine health services due to the COVID-19 pandemic has led to an increase in cases and deaths due to malaria. However, in Franceville, south-east Gabon, no data on malaria cases recorded before, during and after the COVID-19 epidemic has been published. Thus, the objective of this study was to determine the epidemiological characteristics of malaria in Franceville from 2019 to 2021. METHODS: A retrospectively study of malaria cases was performed at the Hôpital de l'Amitié Sino-Gabonaise (HASG). Information regarding age, gender, malaria diagnosis by microscopy and hematology cell count were collected from laboratory registers from June 2019 to December 2021. Malaria data were analyzed and correlated with seasonal variations. RESULTS: The data of 12,695 febrile patients were collected from the laboratory registers of the HASG, among which 4252 (33.5%) patients were found positive for malaria. The malaria prevalence was 37.5% in 2020 year. This prevalence was highest compared to the 2019 (29.6%) and 2021 (31.5%) year (p < 0.001). During the short rainy season (October to December), a large increase in malaria cases was observed all three year, from 2019 to 2021 (p > 0.05). CONCLUSION: The prevalence of malaria in Franceville was very high during COVID-19 pandemic. It is therefore necessary to strengthen existing interventions and implement more effective interventions.

Inflammatory cytokine responses in children with asymptomatic malaria infection living in rural, semi-urban and urban areas in south-eastern Gabon.

Cytokines are soluble mediators of the immune response, and their evolution influences the disease outcome. Gaining knowledge on cytokines has become important, as they can constitute biomarkers allowing the diagnosis of malaria and preventing severe forms of the disease. Here, we investigated 10 cytokines and their circulating levels in asymptomatic Gabonese children with Plasmodium falciparum infection living in urban, semi-urban and rural areas. Blood samples were collected from 273 schoolchildren (153 uninfected and 120 infected) aged 6 to 192 months. Hematological parameters were determined and P. falciparum diagnosis was performed using a rapid diagnosis test, microscopy and nested polymerase chain reaction (PCR). Plasma pro- [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12p70, IL-17A and IL-22] and anti-inflammatory [IL-10, IL-4, IL-13 and transforming growth factor (TGF)-ß] cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and compared between asymptomatic-infected and uninfected children. Results revealed that without distinction of area, IL-10 and IL-6 levels were higher in infected compared to uninfected children; however, the pro- and anti-inflammatory ratios (IL-6/IL-10 and TNF-α/IL-10) were similar. Furthermore, with area distinction significantly elevated levels of IL-10 in these asymptomatic children were always accompanied by either significantly low or high levels of a proinflammatory cytokine. Also, comparison between asymptomatic-infected children from the three areas showed significantly lower IL-17A, IL-22 and TGF-ß levels in urban area compared to semi-urban and rural areas. These results suggest that asymptomatic malaria infections induce significantly high inflammatory cytokine levels without modifying the balanced between pro- and anti-inflammatory cytokines and underline the higher exposure to infections of children in rural areas.

Molecular prevalence of intestinal parasites infections in children with diarrhea in Franceville, Southeast of Gabon.

BACKGROUND: Pediatric diarrhea caused by a range of pathogens, including intestinal parasites, is one of main causes of death among children under 5 years of age. The distribution of these parasitic infections overlaps in many environmental, socioeconomic and epidemiological settings. Their distribution and prevalence varies from region to region. In the current study, we assess the prevalence of intestinal parasites among pediatric patients with syndromic diarrheal disease living in Franceville, Gabon. METHODS: A cross-sectional study conducted in the Amissa Bongo Regional Hospital and Chinese-Gabonese Friendship Hospital in Franceville, between November 2016 and August 2017, enrolled a total of 100 diarrheic children between 0 and 180 months of age. Parasite detection in stool samples was performed using molecular diagnostic by PCR. Difference in means were tested by Student's t test and ANOVA while principal component analysis was used to determine the correlation between parasite distributions and age groups. RESULTS: The overall prevalence of intestinal parasite infection was 61% (61/100). Hymenolepis sp and Cryptosporidium hominis/parvum were the most common parasites (31 and 19%, respectively), followed by Encephalitozoon intestinalis (15%), Trichuris trichiura (4%), Dientamoeba fragilis (4%), and Enterocytozoon bieneusi (2%). The polyparasitism rate was 19.7%, with 83.3% double and 16.7% triple infections. Protozoan infections (66.7%) were more prevalent than helminths infections (33.3%). Seasonal association of the circulation of intestinal parasite was statistically significant (p = 0.03). Correlations between different parasites was also observed. CONCLUSION: The prevalence of intestinal parasitic infections is highest in diarrheic pediatric children. The prevalence of parasitic infections indicates that protozoa and helminths are the most common parasites in the Franceville environment. This study reinforces the importance of routine examination of diarrheic stool samples for the diagnostic of intestinal parasites. Further analyses are required to better understand the local epidemiology and risk factors associated with the transmission of intestinal parasites in Franceville, Gabon. KEYSWORDS: diarrhea, children, intestinal parasitic infections, molecular diagnostic, Franceville, Gabon.

Malaria Prevalence in Asymptomatic and Symptomatic Children Living in Rural, Semi-Urban and Urban Areas in Eastern Gabon.

BACKGROUND: Malaria remains a major public health issue in the world despite a decline in the disease burden. However, though symptomatic malaria is diagnosed and treated, asymptomatic infections remain poorly known and support transmission. This study assessed the prevalence of symptomatic and asymptomatic Plasmodium spp. infections in three areas in Gabon to monitor and evaluate the impact of malaria. METHODS AND RESULTS: A cross-sectional study was conducted in three areas of Gabon. Febrile and afebrile children aged 6 months to 15 years were included in this study. Malaria prevalence was determined by microscopy of and using rapid diagnostic test (RDT). Plasmodium spp. species were identified by PCR according to the Snounou method. The data were recorded in Excel, and the statistical analyses were performed using the software R version R 64 × 3.5.0. A total of 2381(333 asymptomatic and 107 symptomatic) children were included. The overall prevalence of malaria was 40% (952/2381), with the majority (77% symptomatic and 98% asymptomatic) of infections caused by Plasmodium falciparum. A high prevalence of malaria was found in infected children in rural and semi-rural areas. In these two areas, a higher prevalence of Plasmodium malariae was observed in asymptomatic. Furthermore, mixed infections were more prevalent in asymptomatic children than in symptomatic. CONCLUSION: This study showed that the prevalence of Plasmodium spp. infection varied according to the regions. The main species was Plasmodium falciparum, but in asymptomatic children the prevalence of Plasmodium malariae was high in rural areas. To help fight malaria more effectively asymptomatic infections should be taken into account and treated.

High prevalence of asymptomatic Anaplasma spp. infection in school-aged children in southeastern Gabon.

OBJECTIVES: The objective of this study was to evaluate the detection rates of asymptomatic Anaplasma spp. and Ehrlichia spp. infections in children in southeastern Gabon. METHODS: We conducted a cross-sectional study among school-aged children in southeastern Gabon between May and June 2021. Blood samples were collected. Anaplasmataceae, Anaplasma spp., and Ehrlichia spp. were detected by microscopy and polymerase chain reaction. RESULTS: Of the 452 blood samples collected, 57.5% (n/N=260/452) of the samples were positive for Anaplasma spp. and/or Ehrlichia spp. by microscopy, 86.9% (n/N=393/452) of the samples were positive for both Anaplasmataceae and Anaplasma spp., and none of the samples were found positive for Ehrlichia spp. PCR was more sensitive and specific than microscopy for detection of Anaplasma spp.. CONCLUSIONS: In our study, a significant number of positive blood samples for Anaplasma spp. were found in school-aged children in southeastern Gabon. Further studies are needed to determine the prevalence of different species of Anaplasma, their pathogenicity, and their transmission patterns.

Molecular Prevalence of Diarrheal Pathogens in Children with Acute Diarrhea in Southeastern Gabon.

Diarrheal diseases are a major cause of morbidity and mortality in infants and young children, particularly in sub-Saharan countries. In Gabon, there are few data on the prevalence of diarrheal pathogens in children. The aim of this study was to assess the prevalence of diarrheal pathogens in children with diarrhea in southeastern Gabon. Stool samples (n = 284) from Gabonese children 0 to 15 years of age with acute diarrhea were analyzed using polymerase chain reaction targeting 17 diarrheal pathogens. At least one pathogen was detected in 75.7% of samples (n = 215). Coinfection with multiple pathogens was observed in 44.7% of patients (n = 127). Diarrheagenic Escherichia coli was the most commonly detected pathogen (30.6%, n = 87), followed by adenovirus (26.4%, n = 75), rotavirus (16.9%, n = 48), Shigella sp. (16.5%, n = 47), Giardia duodenalis (14.4%, n = 41), norovirus GII (7.0%, n = 20), sapovirus (5.6%, n = 16), Salmonella enterica (4.9%, n = 14), astrovirus (4.6%, n = 13), Campylobacter jejuni/coli (4.6%, n = 13), bocavirus (2.8%, n = 8), and norovirus GI (2.8%, n = 8). Our study provides useful information on the possible causes of diarrheal diseases affecting children in southeastern Gabon. A similar study with a control group of healthy children is needed to assess the burden of the disease attributed to each pathogen.

Cytokine response in asymptomatic and symptomatic Plasmodium falciparum infections in children in a rural area of south-eastern Gabon.

Plasmodium falciparum is a parasite that causes asymptomatic or symptomatic malaria infections in humans depending on various factors. These infections are also a major cause of anemia in intertropical countries such as Gabon. Past studies have clearly demonstrated that inflammatory markers such as cytokines play a key role in the pathogenesis of malaria disease. However, the clinical manifestations of severe malaria vary according to the level of transmission and more information is needed to gain a better understanding of the factors involved. As such, the objective of this study was to investigate the circulating levels of nine cytokines in asymptomatic and symptomatic P. falciparum infections in Gabonese children and their roles in the pathogenesis of anemia. Blood samples were collected from 241 children aged 3 to 180 months in Lastourville, south-eastern Gabon. Diagnosis of P. falciparum infection was performed using Rapid Diagnosis Tests, microscopy and nested PCR. Levels in the plasma of the Th1 (IFN-γ, TNF-α, IL-6 and IL-12p70), Th17 (IL-17A and IL-22) and Th2 (IL-10, IL-4 and IL-13) cytokines were measured by ELISA. Data showed that IL-6, IFN-γ, IL-12p70, IL-10, and IL-13 levels were significantly higher in children with symptomatic P. falciparum infection compared to uninfected children. IL-10 levels were significantly higher in symptomatic children than in asymptomatic children, who had moderately increased levels compared to uninfected controls. Moreover, only IL-10 and IL-6 levels were significantly higher in children with severe malarial anemia compared to children with uncomplicated malaria who had significantly lower IL-10 levels than children with moderate malarial anemia. These data indicate that the progression of P. falciparum infection towards an advanced stage in children is accompanied by a significant increase in type Th1 and/or Th2 cytokines. These inflammatory mediators could serve as potential predictors of anemia for malaria patients.

Pentaclethra eetveldeana Leaves from Four Congo-Brazzaville Regions: Antioxidant Capacity, Anti-Inflammatory Activity and Proportional Accumulation of Phytochemicals.

Oxidative stress and inflammation play a key role in the occurrence of neurodegenerative diseases. Traditionally, Pentaclethra eetveldeana leaves are used in dementia treatment. Therefore, this study aimed to evaluate the antioxidant and anti-inflammatory activities as well as the phytochemical composition of Pentaclethra eetveldeana leaves from four Congo-Brazzaville regions. The 1.2-diphenyl-1-picrylhydrazyl radical-scavenging, ß-carotene bleaching and molybdenum reduction assays were used to assess the antioxidant activity. The protein denaturation and erythrocyte membrane stabilization tests were used to analyze the anti-inflammatory activity. Phytochemical screening, the quantification of polyphenols by spectrophotometry, as well as the determination of extraction yields were carried out. It was found that the extracts reduced molybdenum; furthermore, compared to ascorbic acid, they showed better antiradical activity and inhibited lipid peroxidation. Moreover, globally, the membrane-stabilizing power of the aqueous extracts was superior or comparable to diclofenac, while the same extracts were less effective for the inhibition of denaturation. All of the aqueous extracts contained polyphenols, saponins, alkaloids, anthraquinones, reducing sugar and cardiotonic glycosides. The total polyphenols, tannins and proanthocyanidins are produced proportionally from one region to another. Finally, the leaves from Brazzaville and Boundji contain flavonols, while those from Makoua and Owando contain flavones. Thus, Pentaclethra eetveldeana leaves contribute to traditional dementia treatment through their antioxidant and anti-inflammatory properties.

Knowledge, Attitude and Practice during the COVID-19 Pandemic in South-East Gabon.

COVID-19 is an emerging respiratory disease; it was declared a global pandemic by the World Health Organization. This survey aimed to describe the knowledge, attitudes, perception and practices of the Gabonese public towards COVID-19. This study was performed on 1016 participants. All participants filled in the questionnaire voluntarily, reporting demographic characteristics and answering questions assessing their level of knowledge, attitudes, perceptions and practice towards COVID-19. Among participants, there were 535 men and 476 women. The mean age of the participants was 33.2 ± 16.7 years old. Almost all participants (98.1%) said that they had heard about COVID-19 but only 2.8% knew the pathogenic agent responsible for COVID-19. More than 80% knew that the disease could be transmitted by greeting infected people (87.3%), kissing an infected person (90.0%), touching an infected doorknob (83.5%) and attending meetings (83.9%). The mean knowledge score was higher among younger than older participants, higher among participants living in urban areas than those living in rural areas and higher among participants with higher levels of education than those with lower levels of education. In general, respondents had good knowledge of COVID-19 and a positive attitude towards using protective measures; however, there were differences according to gender, age group, place of residence, professional group and level of education.

High prevalence of genotypes associated with sulfadoxine/pyrimethamine resistance in the rural area of Fougamou, Gabon.

OBJECTIVES: Pregnancy-associated malaria (PAM) is a complex form of malaria. To prevent PAM, several African countries have adopted intermittent preventive treatment with sulfadoxine/pyrimethamine (IPT-SP). However, resistance to SP has been reported, associated with mutations in the genes Plasmodium falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr). The aim of this study was to investigate the prevalence of mutations in Pfdhfr and Pfdhps in P. falciparum isolates from rural areas of Gabon. METHODS: A cross-sectional survey of febrile patients (n = 202) who consulted Fougamou Health Center between February-May 2016 was performed. DNA was extracted from patient samples and the Pfdhfr and Pfdhps genes were genotyped using PCR-RFLP. Statistical analyses were performed. RESULTS: The malaria prevalence in febrile patients included in the study was 60.4% (122/202). The main parasite species was P. falciparum (96.7%; 118/122), followed by Plasmodium malariae (3.3%; 4/122). Genotypes on codons 16, 51, 59 and 108 of Pfdhfr were highly mutated (>96%). In Pfdhps, codons 436, 437, 540 and 613 also expressed high mutation rates. The prevalence of triple mutations of Pfdhfr VIRNI and AIRNI was 12.1% and 84.5%, respectively. The prevalence of mutant haplotypes of Pfdhps SGEA, SGKA and AGEA was 37.9%, 25.9% and 12.1%, respectively. The prevalence of quadruple mutants IRN-A and IRN-G was 20.0% and 93.1%, respectively, whereas quintuple mutants were found at 57.8% (IRN-GE) and 5.0% (IRN-AE). CONCLUSION: Our data show a high prevalence of genotypes associated with SP resistance. Clinical trials to investigate the efficacy of IPT-SP are much needed.

Differential Prevalences of Pfmdr1 Polymorphisms in Symptomatic and Asymptomatic Plasmodium falciparum Infections in Lastoursville: A Rural Area in East-Central Gabon.

PURPOSE: Plasmodium falciparum malaria remains a major public health challenge in sub-Saharan Africa. Plasmodium falciparum drug resistance mediated by polymorphisms in the Pfmdr1 gene contributes to the persistence of the disease on the African continent. This study investigated P. falciparum infection features and differences in the Pfmdr1 genotypes between symptomatic and asymptomatic malaria cases in a rural area in east-central Gabon. PATIENTS AND METHODS: A total of 875 children aged from 5 to 185 months were screened for P falciparum infection using Optima-IT® rapid diagnostic tests and standard microscopy. Pfmdr1 polymorphisms at codons 86, 184 and 1246 were investigated using PCR-RFLP. RESULTS: Among the 448 P. falciparum-infected children, 57.08% (n=250) were symptomatic and 42.92% (n=198) were asymptomatic (p < 0.0001). In a sub-set of 79 isolates, the Pfmdr1 wild-type N86 was more prevalent in symptomatic (100%) than in asymptomatic infections (70.7%) (p=0.007). The mutant 86Y and mixed 86N/Y genotypes were observed only in asymptomatic infections. The Y184 and 184F genotype prevalences (39.1% vs 19.4% and 60.9% vs 80.6%, respectively) were not significantly different between the two groups (p=0.097). The prevalence of the wild-type D1246 differed significantly between symptomatic (10.3%) and asymptomatic (100%) (p < 0.0001). The NFD and YFD haplotypes were more prevalent in asymptomatic than in symptomatic infections [(61.9% vs 31%; p=0.005) and (16.7% vs 0.0%; p=0.01)], whereas the NYD and YYD haplotypes were not significantly different between the two groups [(21.4% vs 14.3%, p=0.39) and (0.0% vs 7.1%, p=0.24)]. CONCLUSION: Our results confirm a high transmission of P. falciparum infection in rural Gabon, with a high prevalence of asymptomatic carriage. The higher prevalences of wild-type N86 in symptomatic infections and of D1246 in asymptomatic infections suggest a pathogenicity associated with polymorphisms in Pfmdr1. These results highlight the need to monitor the efficacy of artemisinin-based combination therapies in Gabon.

Molecular identification of head lice collected in Franceville (Gabon) and their associated bacteria.

BACKGROUND: Pediculus humanus, which includes two ecotypes (body and head lice), is an obligate bloodsucking parasite that co-evolved with their human hosts over thousands of years, thus providing a valuable source of information to reconstruct the human migration. Pediculosis due to head lice occurred each year throughout the world and several pathogenic bacteria, which are usually associated with body lice, are increasingly detected in them. In Gabon, where this pediculosis is still widespread, there is a lack of data on genetic diversity of head lice and their associated bacteria. METHODS: This study aimed to investigate the phylogeny of head lice collected in Gabon and their associated bacteria, using molecular tools. Between 26 March and 11 April 2018, 691 head lice were collected from 86 women in Franceville. We studied the genetic diversity of these lice based on the cytochrome b gene, then we screened them for DNA of Bartonella quintana, Borrelia spp., Acinetobacter spp., Yersinia pestis, Rickettsia spp., R. prowazekii, Anaplasma spp. and C. burnetii, using real time or standard PCR and sequencing. RESULTS: Overall 74.6% of studied lice belonged to Clade A, 25.3% to Clade C and 0.1% to Clade E. The phylogenetic analysis of 344 head lice yielded 45 variable positions defining 13 different haplotypes from which 8 were novel. Bacterial screening revealed the presence of Borrelia spp. DNA in 3 (0.4%) of 691 head lice belonging to Clade A and infesting one individual. This Borrelia is close to B. theileri (GenBank: MN621894). Acinetobacter spp. DNA has been detected in 39 (25%) of the 156 screened lice; of these 13 (8.3%) corresponded to A. baumannii. Acinetobacter nosocomialis (n = 2) and A. pittii (n = 1) were also recorded. CONCLUSIONS: To of our knowledge, this study is the first to investigate the genetic diversity of head lice from Gabon. It appears that Clade C is the second most important clade in Gabon, after Clade A which is known to have a global distribution. The detection of Borrelia spp. DNA in these lice highlight the potential circulation of these bacteria in Gabon.

High Circulation of Malaria and Low Prevalence of Bacteremia in Febrile and Afebrile Children in Northeastern Gabon.

The epidemiology of febrile illness etiologies is under-explored in resource-poor settings. Establishing a local repertory of microorganisms circulating in blood of febrile and afebrile people is important for physicians. Blood was collected from 428 febrile and 88 afebrile children in Makokou (Gabon) and analyzed using polymerase chain reaction. Plasmodium spp. were the pathogens, which were most detected in febrile children (69.6%; 298/428) and in afebrile children (31.8%; 28/88) (P < 0.0001). Plasmodium falciparum was the most prevalent species in both febrile and afebrile children (66.8% and 27.3%, respectively). No differences were observed between febrile and afebrile children for Plasmodium malariae and Plasmodium ovale (8.2% versus 10.2% and 3.3% versus 3.4%, respectively). Triple infection with P. falciparum, P. malariae, and P. ovale was also detected in 1% of febrile children (4/428). Filariasis due to Mansonella perstans was detected in 10 febrile patients (2.3%), whereas Loa loa was detected in both febrile and afebrile children (1.4% and 2.3%, respectively). Bacterial DNA was detected in only 4.4% (19/428) of febrile children, including 13 (68.4%) who were coinfected with at least one Plasmodium species. These were Haemophilus influenzae (1.6%, 7/428), Streptococcus pneumoniae and Staphylococcus aureus (1.2%, 5/428), and Rickettsia felis (0.9%, 4/428). Coxiella burnetii, Bartonella spp., Borrelia spp., Tropheryma whipplei, Anaplasma spp., Leptospira spp., Streptococcus pyogenes, and Salmonella spp. were not detected. This study also highlights the over-prescription and the overuse of antibiotics and antimalarials. Overall, malaria remains a major health problem in Makokou. Malaria control measures must be reconsidered in this region.

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.

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.

In vitro antiplasmodial activity of crude extracts of Tetrapleura tetraptera and Copaifera religiosa.

BACKGROUND: Malaria remains a major public health problem, especially in tropical and subtropical regions because of the emergence and widespread of antimalarial drug resistance. Traditional medicine represents one potential source of new treatments. Here, we investigated the in vitro antiplasmodial activity of bark extracts from two Fabaceae species (Tetrapleura tertaptera and Copaifera religiosa) traditionally used to treat malaria symptoms in Haut-Ogooué province, Gabon. FINDINGS: The antiplasmodial activity of dichloromethane and methanolic extracts was tested on P. falciparum strains FCB (chloroquine-resistant) and 3D7 (chloroquine-sensitive) and on fresh clinical isolates, using the DELI method. Host cell toxicity was analyzed on MRC-5 human diploid embryonic lung cells using the MTT test.The dichloromethane extracts of the two plants had interesting activity (IC50 between 8.5 ± 4.7 and 13.4 ± 3.6 µg/ml). The methanolic extract of Tetrapleura tetraptera was less active (IC50 around 30 µg/ml) and the methanolic extract of Copaifera religiosa was inactive. The selectivity index (toxicity/antiplasmodial activity) of the dichloromethane extract of Tetrapleura tetraptera was high (around 7), while the dichloromethane extract of Copaifera religiosa had the lowest selectivity (0.6). The mean IC50 values for field isolates were less than 1.5 µg/ml for dichloromethane extracts of both plants, while methanolic extracts of Tetrapleura tetraptera showed interesting activity (IC50 = 13.1 µg/ml). The methanolic extract of Copaifera religiosa was also inactive on field isolates. CONCLUSIONS: Dichloromethane extracts of Tetrapleura tetraptera and Copaifera religiosa, two plants used to treat malaria in Gabon, had interesting antiplasmodial activity in vitro. These data provide a scientific rationale for the traditional use of these plants against malaria symptoms. Bioactivity-guided phytochemical analyses are underway to identify the active compounds.

In vitro antiplasmodial activity and cytotoxicity of nine plants traditionally used in Gabon.

AIM OF THE STUDY: As part of a project to identify new compounds active on malarial parasites, we tested the in vitro antiplasmodial activity of nine plants traditionally used to treat malaria symptoms in Haut-Ogooué Province, South-East Gabon. MATERIALS AND METHODS: Dichloromethane and methanolic extracts of each plant were tested for their antiplasmodial activity on two chloroquine-resistant strains of Plasmodium falciparum (FCB and W2), based on lactate dehydrogenase activity. Cytotoxicity was assessed with the MTT test on MRC-5 human diploid embryonic lung cells. RESULTS: The methanolic extract of Staudtia gabonensis and the dichloromethane extract of Adhatoda latibracteata showed high antiplasmodial activity (IC50<1 µg/ml) and low cytotoxicity, with selectivity indexes of about 58.25 and 16.43, respectively. The methanolic extract of Monodora myristica and the dichloromethane extract of Afromomum giganteum also showed promising activity (1