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1.
Trop Med Int Health ; 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33860600

ABSTRACT

OBJECTIVE: To report the prevalence of polyparasitism during pregnancy in the Lambaréné region of Gabon and its association with newborn birth weight. METHOD: Pregnant women in their third trimester were recruited in a prospective study between November 2011 and March 2015. Parasite infection status was assessed microscopically in stool, urine and blood samples. Maternal demographic and obstetrical characteristics and newborns anthropometric data were collected. Multivariable logistic regression was used to assess the association between low birth weight and polyparasitism. RESULTS: 678 of 927 pregnant women were included for analysis with mean age (SD) of 25 (6.8) years. The analysis showed that 69% (468/678) were infected with at least one parasite (Plasmodium spp., Schistosoma spp., soil-transmitted helminths, filarial infections). This comprised of 38% with monoparasitism and 31% polyparasitism. The proportion of newborn babies with a weight below 2500 g (LBW) in our study was 21% (142/678). Compared to pregnant women without infection, women with monoparasitic infection had adjusted Odds Ratio confidence interval 95% CI (aOR [95%CI]) of 1.6 [0.95-2.73], those with two parasites had aOR 95%CI of 2.63 [1.51-4.62], and those with more than two parasites had aOR of 5.08 [2.5-10.38] for delivering a newborn with low birth weight. CONCLUSION: In Lambaréné, an endemic area for multiple parasite infections, there is a high prevalence of polyparasitism in pregnant women. Polyparasitism is associated with low birth weight. Therefore, there is an urgent need for active screening and treatment of parasite infections in pregnant women to assess the potential public health benefit of such interventions.

2.
Nat Immunol ; 22(5): 654-665, 2021 May.
Article in English | MEDLINE | ID: mdl-33888898

ABSTRACT

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161+CD4+ T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4+ T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.

3.
BMC Infect Dis ; 21(1): 265, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33731022

ABSTRACT

BACKGROUND: Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. METHODS: A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. RESULTS: The overall seroprevalence during 2014-2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. CONCLUSIONS: This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.


Subject(s)
Arboviruses/isolation & purification , Dengue/epidemiology , Zika Virus Infection/epidemiology , Adolescent , Animals , Arbovirus Infections/diagnosis , Arbovirus Infections/epidemiology , Arboviruses/classification , Child , Child, Preschool , Communicable Diseases, Emerging , Dengue/diagnosis , Female , Fever/epidemiology , Fever/virology , Gabon/epidemiology , Humans , Infant , Male , Public Health , Seroepidemiologic Studies , Zika Virus Infection/diagnosis
4.
Int J Infect Dis ; 105: 452-459, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33667697

ABSTRACT

OBJECTIVES: Lymphocytic choriomeningitis virus (LCMV), a human pathogenic arenavirus, is distributed worldwide. However, no human cases have been reported in Africa. This study aimed to investigate the current situation and potential risks of LCMV infection in Gabon, Central Africa. METHODS: A total of 492 human samples were screened to detect LCMV genome RNA and anti-LCMV IgG antibodies using reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. ELISA-positive samples were further examined using a neutralization assay. Viral RNAs and antibodies were also analyzed in 326 animal samples, including rodents, shrews, and bushmeat. RESULTS: While no LCMV RNA was detected in human samples, the overall seroprevalence was 21.5% and was significantly higher in male and adult populations. The neutralization assay identified seven samples with neutralizing activity. LCMV RNA was detected in one species of rodent (Lophuromys sikapusi) and a porcupine, and anti-LCMV IgG antibodies were detected in four rodents and three shrews. CONCLUSIONS: This study determined for the first time the seroprevalence of LCMV in Gabon, and revealed that local rodents, shrews, and porcupines in areas surrounding semi-urban cities posed an infection risk. Hence, LCMV infection should be considered a significant public health concern in Africa.

5.
PLoS One ; 16(2): e0246694, 2021.
Article in English | MEDLINE | ID: mdl-33561169

ABSTRACT

BACKGROUND: Malnutrition and low birth weight (LBW) are two common causes of morbidity and mortality among children in sub-Saharan Africa. Both malnutrition and LBW affect early childhood development with long term consequences that may vary in their degree depending on the geographical setting. This study evaluates growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon from a birth cohort of a malaria in pregnancy clinical trial (NCT00811421). METHOD: A prospective longitudinal birth cohort conducted between 2009 and 2012, included infants that were followed up from birth until their first-year anniversary. The exposure of interest was low birth weight and the outcomes explored were growth represented by weight gain, the nutritional status including stunting, wasting and underweight, and the mortality. Scheduled follow-up visits were at one, nine and 12 months of age. Logistic regression was used to assess the association between low birth weight and growth and nutritional outcomes, and cox regression was used for mortality. RESULT: A total of 907 live-born infants were included in the analysis. The prevalence of LBW was 13% (115). At one month of life, out of 743 infants 10% and 4% presented with stunting and underweight, respectively, while these proportions increased at 12 months of life to 17% and 21%, respectively, out of 530 infants. The proportion of infants with wasting remained constant at 7% throughout the follow-up period. Stunting and underweight were associated with LBW, adjusted odds ratio (aOR): 2.6, 95% confidence interval (95%CI): 1.4-4.9 and aOR: 4.5, 95%CI: 2.5-8.1, respectively. Preterm birth was associated with stunting, aOR: 2.7, 95%CI: 1.2-6.3 and underweight, aOR: 5.4, 95%CI: 1.7-16.1 at one month of life. Infants with LBW were at higher hazard of death during the first year of life, adjusted hazard ratio 4.6, 95%CI: 1.2-17.0. CONCLUSION: Low birthweight infants in Gabon are at higher risks of growth and nutritional deficits and mortality during the first year of life. Tailored interventions aiming at preventing adverse pregnancy outcomes including LBW, early detection and appropriate management of growth, and nutritional deficits in infants are necessary in Gabon.

6.
PLoS Negl Trop Dis ; 15(2): e0008861, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33566822

ABSTRACT

BACKGROUND: In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. METHODS: Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. RESULTS: Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. CONCLUSION: Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians' diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.

7.
Wien Klin Wochenschr ; 133(9-10): 500-508, 2021 May.
Article in English | MEDLINE | ID: mdl-33398458

ABSTRACT

Medical research in sub-Saharan Africa is of high priority for societies to respond adequately to local health needs. Often enough it remains a challenge to build up capacity in infrastructure and human resources to highest international standards and to sustain this over mid-term to long-term periods due to difficulties in obtaining long-term institutional core funding, attracting highly qualified scientists for medical research and coping with ever changing structural and political environments. The Centre de Recherches Médicales de Lambaréné (CERMEL) serves as model for how to overcome such challenges and to continuously increase its impact on medical care in Central Africa and beyond. Starting off as a research annex to the Albert Schweitzer Hospital in Lambaréné, Gabon, it has since then expanded its activities to academic and regulatory clinical trials for drugs, vaccines and diagnostics in the field of malaria, tuberculosis, and a wide range of poverty related and neglected tropical infectious diseases. Advancing bioethics in medical research in Africa and steadily improving its global networks and infrastructures, CERMEL serves as a reference centre for several international consortia. In close collaboration with national authorities, CERMEL has become one of the main training hubs for medical research in Central Africa. It is hoped that CERMEL and its leitmotiv "to improve medical care for local populations" will serve as an inspiration to other institutions in sub-Saharan Africa to further increase African capacity to advance medicine.

9.
Vaccines (Basel) ; 8(3)2020 Jul 11.
Article in English | MEDLINE | ID: mdl-32664597

ABSTRACT

Helminth infections are common in sub-Saharan Africa. Besides direct clinical effects, a bias towards a T helper type 2 (Th2) cell immune response is observed. The consequences of parasite infection during pregnancy for the mother and particularly for the fetus and the newborn can be severe and may include impaired immune response during acute infection and vaccination. Here, we present data of immune responses to vaccines given within the expanded program on immunization (EPI) of infants born to helminth infected or non-infected mothers. The study was conducted in Lambaréné and surroundings, Gabon. Maternal helminth infection was diagnosed microscopically using the Kato-Katz method for soil-transmitted helminths (STH), urine filtration for Schistosoma haematobium infections and the saponin-based method for filarial infections. Plasma antibody levels to different vaccine antigens were measured in mothers and their offspring by enzyme-linked immunosorbent assay (ELISA) at different timepoints. We found 42.3% of the mothers to be infected with at least one helminth species. Significantly lower anti-tetanus toxoid immunoglobulin (Ig) G was detected in the cord blood of infants born to helminth infected mothers. Following vaccination, immune responses of the infants to EPI vaccines were similar between the two groups at nine and 12 months. Even though infection with helminths is still common in pregnant women in Gabon, in our setting, there was no evidence seen for a substantial effect on infants' immune responses to vaccines given as part of the EPI.

10.
J Viral Hepat ; 27(11): 1234-1242, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32564517

ABSTRACT

Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.

11.
PLoS Negl Trop Dis ; 14(6): e0008423, 2020 06.
Article in English | MEDLINE | ID: mdl-32589632

ABSTRACT

BACKGROUND: It is unclear whether individual treatment of scabies is similarly effective compared to household treatment. This study compared these two treatment strategies with topical benzyl benzoate for treating scabies in Lambaréné, Gabon. METHODS: Participants presenting with uncomplicated scabies were randomized into either the Individual Treatment group, where only the affected participants received treatment, or the Household Treatment group, where all family members were treated in parallel to the affected participants regardless of signs and symptoms. The primary endpoint was clinical cure after 28 days; the secondary endpoint was the proportion of affected household members per household after 28 days. RESULTS: After 28 days, from a total of 79 participants assessed, 67% (n = 53) were clinically cured; 59% (20/34) in the Individual Treatment group and 73% (33/45) in the Household Treatment group. Participants in the Household Treatment group had about twice the odds of being cured (odds ratio 1.9, 95% confidence interval: 0.8-4.9; p = 0.17). For the secondary outcome, an effect of similar size was observed. CONCLUSIONS: Our findings show that treating close contacts of persons affected by scabies may be beneficial to patients and contacts, however, the benefit was less pronounced than anticipated and further research is needed to definitively answer this question.


Subject(s)
Family Characteristics , Insecticides/therapeutic use , Scabies/drug therapy , Adolescent , Adult , Benzoates/therapeutic use , Child , Child, Preschool , Female , Gabon , Humans , Infant , Male , Middle Aged , Young Adult
12.
Vaccine ; 38(27): 4263-4272, 2020 Jun 02.
Article in English | MEDLINE | ID: mdl-32386747

ABSTRACT

BACKGROUND: Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. METHODS: Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). RESULTS: The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. CONCLUSION: Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.

13.
Am J Trop Med Hyg ; 103(1): 325-333, 2020 07.
Article in English | MEDLINE | ID: mdl-32431272

ABSTRACT

Schistosomiasis is a parasitic infection highly prevalent in Central Africa where it is co-endemic with many other parasitic infections, including soil-transmitted helminths (STHs). For its optimal control, there is a need of descriptive epidemiological data for each endemic region. The objective of the present study was to determine the epidemiological situation around schistosomiasis in Lambaréné, Gabon. A cross-sectional study was conducted among schoolchildren. One urine sample per day was collected on three consecutive days for the diagnosis of schistosomiasis using a urine filtration technique. One stool sample was collected for the detection of Schistosoma spp. and STH spp. eggs using the Kato-Katz technique, and for larvae, using the coproculture technique. A total of 614 schoolchildren were included in the analysis. The overall prevalence of schistosomiasis and STH infections was 26% (159/614) and 15% (70/473), respectively. Human-freshwater contact was the main risk factor for schistosomiasis in the area (relative risk (RR) = 2.96 [2.20-4.00], P < 0.001). Hematuria (RR = 5.53 [4.30-7.10], P < 0.001) and proteinuria (RR = 2.12 [1.63-2.75], P < 0.001) as well as infection with Trichuris trichiura (RR = 1.86 [1.33-2.61], P = 0.002) and Ascaris lumbricoides (RR = 1.96 [1.19-3.21], P = 0.039) were associated with an increased risk of schistosomiasis. Trichuris trichiura was the highest prevalent STH species in the area. Our study reports a moderate prevalence for schistosomiasis with human-water contact as the main risk factor, whereas the prevalence of STH infections appears to be low. Our results stress the need for the implementation of WHO recommendations for schistosomiasis control.


Subject(s)
Ascariasis/epidemiology , Schistosomiasis haematobia/epidemiology , Trichuriasis/epidemiology , Adolescent , Albendazole/therapeutic use , Anthelmintics/therapeutic use , Ascariasis/drug therapy , Child , Coinfection/epidemiology , Cross-Sectional Studies , Culture Techniques , Feces/parasitology , Female , Gabon/epidemiology , Hematuria/epidemiology , Hookworm Infections/drug therapy , Hookworm Infections/epidemiology , Humans , Male , Praziquantel/therapeutic use , Prevalence , Proteinuria/epidemiology , Risk Factors , Schistosomiasis haematobia/drug therapy , Strongyloidiasis/drug therapy , Strongyloidiasis/epidemiology , Trichuriasis/drug therapy
14.
BMC Med ; 18(1): 47, 2020 02 25.
Article in English | MEDLINE | ID: mdl-32098634

ABSTRACT

BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.


Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/pathogenicity , Amodiaquine/pharmacology , Antimalarials/pharmacology , Artemether, Lumefantrine Drug Combination/pharmacology , Artemisinins/pharmacology , Child, Preschool , Drug Combinations , Female , Humans , Infant , Male
15.
Sci Rep ; 10(1): 2080, 2020 02 07.
Article in English | MEDLINE | ID: mdl-32034188

ABSTRACT

The causes of infections in pediatric populations differ between age groups and settings, particularly in the tropics. Such differences in epidemiology may lead to misdiagnosis and ineffective empirical treatment. Here, we investigated the current spectrum of pathogens causing febrile diseases leading to pediatric hospitalization in Lambaréné, Gabon. From August 2015 to March 2016, we conducted a prospective, cross-sectional, hospital-based study in a provincial hospital. Patients were children ≤ 15 years with fever ≥ 38 °C and required hospitalization. A total of 600 febrile patients were enrolled. Malaria was the main diagnosis found in 52% (311/600) patients. Blood cultures revealed septicemia in 3% (17/593), among them four cases of typhoid fever. The other causes of fever were heterogeneously distributed between both bacteria and viruses. Severe infections identified by Lambaréné Organ Dysfunction Score (LODS) were also most often caused by malaria, but children with danger signs did not have more coinfections than others. In 6% (35/600) of patients, no pathogen was isolated. In Gabon, malaria is still the major cause of fever in children, followed by a bacterial and viral disease. Guidelines for both diagnosis and management should be tailored to the spectrum of pathogens and resources available locally.


Subject(s)
Fever/etiology , Infections/complications , Child , Child, Preschool , Cross-Sectional Studies , Female , Gabon/epidemiology , Hospitals/statistics & numerical data , Humans , Infant , Infections/epidemiology , Infections/microbiology , Infections/virology , Malaria/complications , Malaria/epidemiology , Male , Organ Dysfunction Scores , Prospective Studies , Sepsis/complications , Sepsis/epidemiology , Typhoid Fever/complications , Typhoid Fever/epidemiology
16.
J Clin Microbiol ; 58(5)2020 04 23.
Article in English | MEDLINE | ID: mdl-32102854

ABSTRACT

Microscopy and rapid diagnostic tests (RDTs) are the main diagnostic tools for malaria but fail to detect low-density parasitemias that are important for maintaining malaria transmission. To complement existing diagnostic methods, an isothermal reverse transcription-recombinase polymerase amplification and lateral flow assay (RT-RPA) was developed. We compared the performance with that of ultrasensitive reverse transcription-quantitative PCR (uRT-qPCR) using nucleic acid extracts from blood samples (n = 114) obtained after standardized controlled human malaria infection (CHMI) with Plasmodium falciparum sporozoites. As a preliminary investigation, we also sampled asymptomatic individuals (n = 28) in an area of malaria endemicity (Lambaréné, Gabon) to validate RT-RPA and assess its performance with unprocessed blood samples (dbRT-RPA). In 114 samples analyzed from CHMI trials, the positive percent agreement to uRT-qPCR was 90% (95% confidence interval [CI], 80 to 96). The negative percent agreement was 100% (95% CI, 92 to 100). The lower limit of detection was 64 parasites/ml. In Gabon, RT-RPA was 100% accurate with asymptomatic volunteers (n = 28), while simplified dbRT-RPA showed 89% accuracy. In a subgroup analysis, RT-RPA detected 9/10 RT-qPCR-positive samples, while loop-mediated isothermal amplification (LAMP) detected 2/10. RT-RPA is a reliable diagnostic test for asymptomatic low-density infections. It is particularly useful in settings where uRT-qPCR is difficult to implement.

17.
Int J Infect Dis ; 91: 129-136, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31821892

ABSTRACT

OBJECTIVES: Dengue outbreaks, mainly caused by dengue virus serotype 2 (DENV-2), occurred in 2007 and in 2010 in Gabon, Central Africa. However, information on DENV infections has been insufficient since 2010. The aim of this study was to investigate the current DENV infection scenario and the risk of repeated infections in Gabon. METHODS: During 2015-2017, serum samples were collected from enrolled febrile participants and were tested for DENV infection using RT-qPCR. DENV-positive samples were analyzed for a history of previous DENV infection(s) using ELISA. The complete DENV genome was sequenced to analyze the phylogeny of Gabonese DENV strains. RESULTS: DENV-3 was exclusively detected, with a high rate of anti-DENV IgG seropositivity among DENV-3-positive participants. DENV-3 showed higher infection rates in adults and the infection was seasonal with peaks in the rainy seasons. Phylogenetic analysis revealed that Gabonese DENV-3 originated from West African strains and has been circulating continuously in Gabon since at least 2010, when the first DENV-3 case was reported. CONCLUSIONS: These findings indicate stable DENV-3 circulation and the risk of repeated DENV infections in Gabon, highlighting the need for continuous monitoring to control DENV infections.


Subject(s)
Dengue Virus/isolation & purification , Dengue/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dengue/virology , Dengue Virus/classification , Dengue Virus/genetics , Female , Gabon/epidemiology , Humans , Infant , Male , Middle Aged , Phylogeny , Real-Time Polymerase Chain Reaction , Seasons , Seroepidemiologic Studies , Serogroup , Young Adult
18.
J Med Virol ; 92(2): 251-256, 2020 02.
Article in English | MEDLINE | ID: mdl-31538666

ABSTRACT

Hepatitis B virus (HBV) infection remains to be a major public health issue worldwide, although there is currently a safe vaccine and effective antiviral treatments. In surveillance of infectious diseases in Gabon, HBV viremia was detected in patients with febrile. Whole-genome sequencing was conducted to characterize the HBV strains currently circulating in Gabon and to investigate HBV genome diversity during viremia. Phylogenetic analysis revealed the existence of former subgenotype A5, which exhibits a particular pattern of distribution from several West and Central African countries to Haiti. Furthermore, sequencing analysis identified two similar HBV strains mixed in one sample, and a very rare 1-base pair insertion in the viral precore region. This insertion caused a frameshift mutation, indicating the production of an aberrant fusion protein of the HBV x and e antigens. Our data showed that the detected HBV strain was possibly in an "evolving" state during viremia, a phase of active replication.

19.
Vaccine ; 38(4): 897-906, 2020 01 22.
Article in English | MEDLINE | ID: mdl-31708182

ABSTRACT

BACKGROUND: We assessed the safety and immunogenicity of the RTS,S/AS01 malaria vaccine in a subset of children identified as HIV-infected during a large phase III randomized controlled trial conducted in seven sub-Saharan African countries. METHODS: Infants 6-12 weeks and children 5-17 months old were randomized to receive 4 RTS,S/AS01 doses (R3R group), 3 RTS,S/AS01 doses plus 1 comparator vaccine dose (R3C group), or 4 comparator vaccine doses (C3C group) at study months 0, 1, 2 and 20. Infants and children with WHO stage III/IV HIV disease were excluded but HIV testing was not routinely performed on all participants; our analyses included children identified as HIV-infected based on medical history or clinical suspicion and confirmed by polymerase chain reaction or antibody testing. Serious adverse events (SAEs) and anti-circumsporozoite (CS) antibodies were assessed. RESULTS: Of 15459 children enrolled in the trial, at least 1953 were tested for HIV and 153 were confirmed as HIV-infected (R3R: 51; R3C: 54; C3C: 48). Among these children, SAEs were reported for 92.2% (95% CI: 81.1-97.8) in the R3R, 85.2% (72.9-93.4) in the R3C and 87.5% (74.8-95.3) in the C3C group over a median follow-up of 39.3, 39.4 and 38.3 months, respectively. Fifteen HIV-infected participants in each group (R3R: 29.4%, R3C: 27.8%, C3C: 31.3%) died during the study. No deaths were considered vaccination-related. In a matched case-control analysis, 1 month post dose 3 anti-CS geometric mean antibody concentrations were 193.3 EU/mL in RTS,S/AS01-vaccinated HIV-infected children and 491.5 EU/mL in RTS,S/AS01-vaccinated immunogenicity controls with unknown or negative HIV status (p = 0.0001). CONCLUSIONS: The safety profile of RTS,S/AS01 in HIV-infected children was comparable to that of the comparator (meningococcal or rabies) vaccines. RTS,S/AS01 was immunogenic in HIV-infected children but antibody concentrations were lower than in children with an unknown or negative HIV status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00866619.

20.
Malar J ; 18(1): 424, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-31842893

ABSTRACT

BACKGROUND: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. METHODS: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti­malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. RESULTS: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. CONCLUSION: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True.


Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use , Artemisinins/therapeutic use , Drug Monitoring/statistics & numerical data , Malaria, Falciparum/drug therapy , Child , Child, Preschool , Drug Combinations , Female , Gabon , Humans , Infant , Male , Plasmodium falciparum/drug effects , Plasmodium falciparum/isolation & purification , Protozoan Proteins/genetics
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