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1.
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
2.
Lancet Infect Dis ; 2020 Sep 11.
Article in English | MEDLINE | ID: mdl-32926834

ABSTRACT

BACKGROUND: Hookworms cause substantial morbidity in children and women of reproductive age. The control strategy of mass drug administration is suboptimal, hence the need for a vaccine. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are involved in the digestion and detoxification of haemoglobin in the hookworm digestive tract. In animal models, vaccination against these antigens resulted in protection from challenge infection. Both vaccine candidates were shown to be safe and well tolerated when administered separately to healthy adults. We assessed the safety and immunogenicity of co-administered Na-GST-1 and Na-APR-1 (M74) vaccines in healthy Gabonese adults. METHODS: This randomised, controlled, double-blind, phase 1, dose-escalation trial was done at the Centre de Recherches Médicales de Lambaréné, in a region of Gabon where N americanus and other helminths are prevalent. Healthy adults aged 18-50 years and living in Lambaréné or the surrounding areas were recruited to the study. Participants were enrolled consecutively into two dose cohorts (30 µg or 100 µg of the experimental vaccines) and randomly assigned in blocks (block size four) to receive three doses of either co-administered Na-GST-1 plus Na-APR-1 (M74; 30 µg or 100 µg of each), adjuvanted with Alhydrogel (aluminium hydroxide gel suspension) together with an aqueous formulation of glucopyranosyl lipid A, or hepatitis B vaccine plus saline (control group). Vaccines were administered intramuscularly on days 0, 28, and 180. The primary endpoint was safety, with immunogenicity a secondary endpoint. The intention-to-treat population was used for safety analyses, whereas for immunogenicity analyses, the per-protocol population was used (participants who received all scheduled vaccinations). Control vaccine recipients for both dose cohorts were combined for the analyses. The trial is registered with ClinicalTrials.gov, NCT02126462. FINDINGS: Between Oct 27, 2014, and Jan 31, 2015, 56 individuals were screened for eligibility, of whom 32 were enrolled and randomly assigned to one of the three study groups (12 each in the 30 µg and 100 µg experimental vaccine groups and eight in the control group). Both study vaccines were well tolerated in both dose groups. The most common adverse events were mild-to-moderate injection-site pain, headache, myalgia, and nausea. No severe or serious adverse events related to the vaccines were recorded. 52 unsolicited vaccine-related adverse events occurred during the study, but there was no difference in frequency between vaccine groups. IgG antibodies were induced to each of the vaccine antigens, with mean IgG levels increasing after each vaccination. Vaccination with 100 µg of each vaccine antigen consistently induced IgG seroconversion (IgG levels above the reactivity threshold). Peak IgG responses were observed 2 weeks after the third vaccine dose for both antigens, with all participants who received the 100 µg doses seroconverting at that timepoint. IgG levels steadily declined until the final study visit 6 months after the third vaccination, although they remained significantly higher than baseline in the 100 µg dose group. INTERPRETATION: Vaccination with recombinant Na-GST-1 and Na-APR-1 (M74) in healthy adults living in N americanus-endemic areas of Gabon was safe and induced IgG to each antigen. To our knowledge, this study is the first to report results of Na-APR-1 (M74) co-administered with Alhydrogel in participants from an N americanus-endemic area. Further clinical development of these vaccines should involve efficacy studies. FUNDING: European Union Seventh Framework Programme.

3.
PLoS Med ; 14(10): e1002402, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28985239

ABSTRACT

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV-GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study. CONCLUSIONS: Our data confirm the acceptable safety and immunogenicity profile of the 2 × 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000919191.


Subject(s)
Adaptive Immunity/drug effects , Ebola Vaccines/administration & dosage , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Age Factors , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Biomarkers/blood , Child , Ebola Vaccines/adverse effects , Ebola Vaccines/immunology , Female , Gabon , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/virology , Humans , Injections, Intramuscular , Male , Middle Aged , Time Factors , Treatment Outcome , Vaccination , Virus Shedding , Young Adult
4.
Am J Trop Med Hyg ; 95(2): 472-80, 2016 Aug 03.
Article in English | MEDLINE | ID: mdl-27352879

ABSTRACT

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action.


Subject(s)
Drug Resistance, Multiple, Bacterial , HIV Infections/epidemiology , HIV/isolation & purification , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Antitubercular Agents/therapeutic use , Child , Child, Preschool , Coinfection , Female , Gabon/epidemiology , HIV/physiology , HIV Infections/diagnosis , HIV Infections/virology , Humans , Incidence , Infant , Isoniazid/therapeutic use , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Prospective Studies , Streptomycin/therapeutic use , Survival Analysis , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology
5.
Malar J ; 15: 160, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26975570

ABSTRACT

BACKGROUND: There is a need for accurate and field-applicable instruments for the evaluation of the quality of anti-malarial drugs. The aim of this study was to determine the diagnostic accuracy of the NanoRam(®), a handheld Raman spectrometer (RS), to identify anti-malarial drugs. METHODS: In total, 289 anti-malarial drugs collected in a randomized field survey in Gabon were evaluated. The samples were compared with authentic products as supplied by the official manufacturer. To determine the sensitivity and specificity of the handheld NanoRam(®) spectrometer in the identification of anti-malarial drugs, a two-gate reversed-flow design was applied. The standards for reporting of diagnostic accuracy studies (STARD) were followed. The index test was the handheld RS. The reference test standards were thin layer chromatography and high performance liquid chromatography with ultraviolet photo diode array detection. RESULTS: The sensitivity [95% confidence interval (95% CI)] and specificity of the RS to correctly identify an anti-malarial drug were 100% (95% CI 94.9-100%) and 96% (95% CI 92.3-99.0%), respectively. The RS could not differentiate between different batches of the same product or different manufacturers of the same product. Intra-observer agreement for 289 samples was 100%. The average time to conduct the RS was 15 s per sample compared to 45 min per sample for TLC. CONCLUSION: The handheld RS holds promise as an easy-to-use, quick and field-applicable instrument for the evaluation of quality of anti-malarial drugs, potentially empowering pharmacists, drug inspectors and medical regulatory authorities. Trial registration NTR4341 (Dutch Trial Registry).


Subject(s)
Antimalarials/chemistry , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Gabon , Pilot Projects , Sensitivity and Specificity
6.
N Engl J Med ; 374(17): 1647-60, 2016 Apr 28.
Article in English | MEDLINE | ID: mdl-25830326

ABSTRACT

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).


Subject(s)
Ebola Vaccines/immunology , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/prevention & control , Membrane Glycoproteins/immunology , Viral Envelope Proteins/immunology , Adult , Antibodies, Viral/blood , Arthritis/etiology , Dermatitis/etiology , Double-Blind Method , Ebola Vaccines/administration & dosage , Ebola Vaccines/adverse effects , Ebolavirus/isolation & purification , Exanthema/etiology , Female , Hemorrhagic Fever, Ebola/immunology , Humans , Male , Middle Aged , Recombinant Proteins , Vesiculovirus , Viremia , Virus Shedding
7.
Future Microbiol ; 10(10): 1553-78, 2015.
Article in English | MEDLINE | ID: mdl-26437872

ABSTRACT

The first clinical Phase III trial evaluating a malaria vaccine was completed in December 2013 at 11 sites from seven sub-Saharan African countries. This systematic review assesses data of Phase I-III trials including malaria-naive adults and adults, children and infants from malaria endemic settings in sub-Saharan Africa. The main endpoint of this systematic review was an analysis of the consistency of efficacy and immunogenicity data from respective Phase I-III trials. In addition, safety data from a pooled analysis of RTS/AS Phase II trials and RTS,S/AS01 Phase III trial were reviewed. The RTS,S/AS01 malaria vaccine may become available on the market in the coming year. If so, further strategies should address challenges on how to optimize vaccine efficacy and implementation of RTS,S/AS01 vaccine within the framework of established malaria control measures.


Subject(s)
Malaria Vaccines/immunology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/prevention & control , Plasmodium falciparum/immunology , Adult , Africa South of the Sahara/epidemiology , Child , Child, Preschool , Humans , Infant , Malaria Vaccines/adverse effects , Malaria, Falciparum/immunology , Malaria, Falciparum/mortality , Vaccination
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