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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.
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.

3.
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.

4.
Wien Klin Wochenschr ; 2021 Jan 04.
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.

5.
BMJ Glob Health ; 5(10)2020 Oct.
Article in English | MEDLINE | ID: mdl-33087393

ABSTRACT

Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study's demographics, the causes of fever identified and the performance of selected biomarkers.

6.
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.

7.
Lancet Infect Dis ; 20(11): 1339-1346, 2020 11.
Article in English | MEDLINE | ID: mdl-32585133

ABSTRACT

BACKGROUND: Loiasis is a highly prevalent helminth infection found in distinct regions of sub-Saharan Africa. The disease has been considered to be of minor clinical significance, but this belief is being increasingly challenged by recent evidence. We aimed to prospectively quantify the overall burden of disease caused by loiasis in an endemic region of Gabon, using disability-adjusted life years (DALYs). METHODS: We did a cross-sectional survey during 2017 and 2018 in rural Gabon. Volunteers underwent diagnostic tests for loiasis and were given a standardised questionnaire on symptoms. Participants reporting eye worm migration or harbouring Loa loa microfilariae were defined as loiasis positive. Morbidity-based DALYs associated with loiasis were estimated for the rural population of Gabon. FINDINGS: Between Sept 1, 2017 and May 31, 2018, 1235 participants residing in 38 villages in the Gabonese departments of Tsamba-Magotsi and Ogooué et des Lacs were screened. 626 (50·8%) of 1232 eligible participants had loiasis. 520 (42·2%) of 1232 participants reported eye worm migration. 478 (93·9%) of 509 individuals with eye worm migration also reported associated pain, and 397 (78·6%) of 505 reported vision disturbances. After correcting for age and sex, loiasis was significantly associated with a variety of symptoms, including transient painful oedema (adjusted odds ratio 1·76 [95% CI 1·37-2·26]) and arthralgia (1·30 [1·01-1·69]). Application of attributable fractions of correlating symptoms resulted in 412·9 (95% CI 273·9-567·7) morbidity-based DALYs per 100 000 people in rural Gabon. INTERPRETATION: Loiasis, with the pathognomonic sign of eye worm migration, appears to not be benign, but severely impeding to affected individuals. Furthermore, loiasis is associated with substantial morbidity, comparable to that of other neglected tropical parasitic diseases. These findings call for reconsideration of L loa as a relevant pathogen in affected populations, with a need for more concerted research and control of these infections. FUNDING: Federal Ministry of Science, Research and Economy of Austria, and the European Union.

9.
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.

10.
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
11.
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.

12.
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
13.
Clin Infect Dis ; 69(12): 2119-2126, 2019 11 27.
Article in English | MEDLINE | ID: mdl-31066448

ABSTRACT

BACKGROUND: Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this prospective study was to characterize the reappearance patterns of ovale parasites. METHODS: P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria. RESULTS: At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi. CONCLUSION: These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.


Subject(s)
Malaria/diagnosis , Malaria/parasitology , Molecular Diagnostic Techniques , Plasmodium ovale , Plasmodium , Follow-Up Studies , Genes, Protozoan , Humans , Malaria/transmission , Molecular Typing , Plasmodium/genetics , Plasmodium ovale/genetics , Polymerase Chain Reaction , RNA, Ribosomal, 18S , Recurrence
14.
Clin Infect Dis ; 68(10): 1763-1768, 2019 05 02.
Article in English | MEDLINE | ID: mdl-30239602

ABSTRACT

During the late phase of the large West-African Ebola virus disease (EVD) outbreak, the majority of patients were cared for in designated treatment centers. However, the preexisting healthcare infrastructure was already overwhelmed by the outbreak. This had a huge impact on other, non-EVD-related diseases, causing an unprecedented increase in morbidity and mortality, which most likely exceeded the toll due to EVD directly. Consequently, a crucial question is how to provide appropriate healthcare and safeguard functionality of a healthcare system that also serves patients not suspected or diagnosed to have EVD. Here, we report on the Lion Heart Medical Center's experience in Sierra Leone and note that a case definition of Ebola that is broader than those commonly applied may be better suited when it is necessary to identify atypically presenting, pauci-symptomatic cases.


Subject(s)
Disease Outbreaks/prevention & control , Health Plan Implementation , Hemorrhagic Fever, Ebola/epidemiology , Hospitals/statistics & numerical data , Patient Care/standards , Disease Management , Hospitals/standards , Humans , Patient Care/methods , Sierra Leone/epidemiology , World Health Organization
15.
Trop Med Int Health ; 23(9): 980-991, 2018 09.
Article in English | MEDLINE | ID: mdl-29956431

ABSTRACT

OBJECTIVES: The recommended microscopy method by WHO to quantify malaria parasitaemia yields inaccurate results when individual leucocyte (WBC) counts deviate from 8000 leucocytes/µl. A method avoiding WBC count assumptions is the Lambaréné method (LAMBA). Thus, this study compared validity and reliability of the LAMBA and the WHO method. METHODS: Three methods for counting parasitaemia were applied in parallel in a blinded assessment: the LAMBA, the WHO method using a standard factor of 8000 leucocytes/µl ['simple WHO method' (sWHO)] and the WHO method using measured WBC counts ['accurate WHO method' (aWHO)]. Validity was assessed by comparing LAMBA and sWHO to the gold standard measurement of aWHO. Reliability was ascertained by computation of intraclass correlation coefficients (ICCs). RESULTS: 787 malaria-positive thick smears were analysed. Parasitaemia as determined by LAMBA and sWHO increasingly deviated from aWHO the more patients' WBCs diverged from 8000/µl. Equations of linear regression models assessing method deviation in percent from gold standard as function of WBC count were y = -0.00608x (95% CI -0.00693 to -0.00524) + 47.8 for LAMBA and y = -0.0125x (95% CI -0.01253 to -0.01247) + 100.1 for sWHO. Comparison of regression slopes showed that the deviation was twice as high for sWHO as for LAMBA (P < 0.001). ICCs were excellent (>90%) for both methods. CONCLUSIONS: The LAMBA has higher validity than the sWHO and may therefore be preferable in resource-limited settings without access to routine WBC-evaluation.


Subject(s)
Malaria/diagnosis , Microscopy/methods , Parasitemia/diagnosis , Humans , Leukocyte Count , Malaria/blood , Parasitemia/blood , Reproducibility of Results
16.
J Infect Dis ; 218(8): 1296-1305, 2018 09 08.
Article in English | MEDLINE | ID: mdl-29800345

ABSTRACT

Background: Diagnosis of malaria is usually based on samples of peripheral blood. However, it is unclear whether capillary (CAP) or venous (VEN) blood samples provide better diagnostic performance. Quantitative differences of parasitemia between CAP and VEN blood and diagnostic performance characteristics were investigated. Methods: Patients were recruited between September 2015 and February 2016 in Gabon. Light microscopy and quantitative polymerase chain reaction (qPCR) measured parasitemia of paired CAP and VEN samples. CAP and VEN performance characteristics using microscopy were evaluated against a qPCR gold standard. Results: Microscopy revealed a median parasitemia of 495/µL in CAP and 429/µL in VEN samples, manifesting in a 16.6% (P = .04) higher CAP parasitemia compared with VEN parasitemia. Concordantly, in qPCR -0.278 (P = .006) cycles were required for signal detection in CAP samples. CAP sensitivity of microscopy relative to the gold standard was 81.5% vs VEN sensitivity of 73.4%, while specificities were 91%. CAP and VEN sensitivities dropped to 63.3% and 45.9%, respectively, for a subpopulation of low-level parasitemias, whereas specificities were 92%. Conclusions: CAP sampling leads to higher parasitemias compared to VEN sampling and improves diagnostic sensitivity. These findings may have important implications for routine diagnostics, research, and elimination campaigns of malaria.


Subject(s)
Blood Specimen Collection/methods , Malaria/blood , Malaria/diagnosis , Parasitemia/diagnosis , Plasmodium/isolation & purification , Adolescent , Adult , Child , Female , Humans , Infant , Malaria/parasitology , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
17.
Article in English | MEDLINE | ID: mdl-29311086

ABSTRACT

Treatment recommendations for Plasmodium malariae and Plasmodium ovale malaria are largely based on anecdotal evidence. The aim of this prospective study, conducted in Gabon, was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated P. malariae or P. ovale species monoinfections or mixed Plasmodium infections. Patients with microscopically confirmed P. malariae, P. ovale, or mixed-species malaria with at least one of these two Plasmodium species were treated with an oral, fixed-dose combination of artemether-lumefantrine for 3 consecutive days. The primary endpoints were per-protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period. Seventy-two participants (42 male and 30 female) were enrolled; 62.5% of them had PCR-corrected mixed Plasmodium infections. Per protocol, PCR-corrected ACPR rates were 96.6% (95% confidence interval [CI], 91.9 to 100) on day 28 and 94.2% (95% CI, 87.7 to 100) on day 42. Considering Plasmodium species independently from their coinfecting species, day 42 ACPR rates were 95.5% (95% CI, 89.0 to 100) for P. falciparum, 100% (exact CI, 84.6 to 100) for P. malariae, 100% (exact CI, 76.8 to 100) for P. ovale curtisi, and 90.9% (95% CI, 70.7 to 100) for P. ovale wallikeri Study drug-related adverse events were generally mild or moderate. In conclusion, this clinical trial demonstrated satisfying antimalarial activity of artemether-lumefantrine against P. ovalewallikeri, P. ovale curtisi, P. malariae, and mixed Plasmodium infections, with per-protocol efficacies of 90% to 100% and without evident tolerability or safety concerns. (This trial was registered in the clinical study database ClinicalTrials.gov under the identifier NCT02528279.).


Subject(s)
Antimalarials/therapeutic use , Artemether/therapeutic use , Lumefantrine/therapeutic use , Plasmodium malariae/pathogenicity , Plasmodium ovale/pathogenicity , Adolescent , Adult , Child , Child, Preschool , Female , Gabon , Humans , Male , Plasmodium malariae/drug effects , Plasmodium malariae/genetics , Plasmodium ovale/drug effects , Plasmodium ovale/genetics , Young Adult
18.
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
19.
Clin Infect Dis ; 65(5): 746-755, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28505356

ABSTRACT

Background: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods: We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. Results: Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. Conclusions: RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.


Subject(s)
Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Th1 Cells/immunology , Th2 Cells/immunology , Case-Control Studies , Cytokines/blood , Humans , Infant , Malaria, Falciparum/epidemiology , Malaria, Falciparum/immunology
20.
Am J Trop Med Hyg ; 96(5): 1205-1214, 2017 May.
Article in English | MEDLINE | ID: mdl-28500816

ABSTRACT

AbstractThe serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In total, 217 patients were included in the study (111 malaria patients and 106 symptomatic controls, defined as malaria-negative febrile patients). Serum lipid levels (mmol/L) were significantly lower in malaria patients compared with those with other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94] versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] = 0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No significant differences were found for apolipoprotein A1, apolipoprotein B, and lipoprotein(a). Cholesterol levels increased toward reference values on day 28 (TC = 3.26-3.98, P < 0.001; HDL-C = 0.43-0.96, P < 0.001; LDL-C = 2.05-2.60, P < 0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day 28; P = 0.130). Lipid profile changes were not correlated with parasitemia or Plasmodium falciparum histidine-rich protein 2 levels. This study confirms characteristic temporary lipid profile changes in malaria. Lipid profile changes demonstrated a good accuracy to discriminate between malaria and other febrile diseases (area under the curve = 0.80 (95% confidence interval = 0.742-0.863, P < 0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid profile changes in malaria. Further studies to elucidate the precise pathways may lead to improved understanding of the underlying pathophysiology.


Subject(s)
Fever/diagnosis , Malaria, Falciparum/diagnosis , Parasitemia/diagnosis , Adult , Antigens, Protozoan/blood , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Diagnosis, Differential , Female , Fever/blood , Gabon , Humans , Lipid Metabolism , Lipoprotein(a)/blood , Malaria, Falciparum/blood , Malaria, Falciparum/parasitology , Male , Parasitemia/blood , Parasitemia/parasitology , Plasmodium falciparum/growth & development , Protozoan Proteins/blood , ROC Curve , Triglycerides/blood
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