julilili42/papers huggingface dataset:
PA-595 Hepatotoxicity associated to N-Acetyltransferase type 2 polymorphisms in TB patients with malaria at Jamot Hospital, Yaoundé, Cameroon
2023-12-01

<h3>Background</h3> Unlike in developed countries, most infectious diseases such as tuberculosis (TB) and malaria continue to cause deaths in low-income countries. Recent studies have shown that hepatotoxicity during TB treatment may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator polymorphism especially in countries with high TB incidence such as Cameroon. The aim of this study was to determine the NAT2 genetic variation associated with hepatotoxicity in TB/Malaria co-infected patients in Jamot Hospital, Yaoundé-Cameroon. <h3>Methods</h3> This was a prospective study from April 2018 - March 2019, aiming to evaluate the genetic variation in NAT2 coding region in TB patients with malaria. A total of 336 pulmonary TB patients with or without malaria infection, aged 15 years and above, were included. Each sputum sample was tested by the Ziehl Neelsen method. Whole blood sample was used for malaria detection using Rapid Diagnostic Test and microscopy. DNA was extracted by chelex method, hepatotoxicity by spectrophotometry, and genotyping done by Polymerase chain reaction followed by restriction fragment length polymorphism analyses with enzymes (KpnI, TaqI, BamHI). <h3>Results</h3> Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) values were significantly higher among TB/malaria co-infected cases compared to TB mono infected patients (p=0.03, p=0.01 respectively). In the group of mono-infected TB patients, a significant difference was found for ALT values between day 1 and day 90 (p=0.021). Similarly, a significant association was found between the development of hepatotoxicity and the presence of a slow acetylator phenotype in TB-malaria co-infected (p=0.026). <h3>Conclusion</h3> The study suggests that TB/malaria co-infections and NAT2 variant phenotype are risk factors for hepatoxicity induction. Therefore, for a more efficient care, evaluation of NAT2 genotypes might be essential to reduce drug interactions and liver toxicity in case of coinfections.
PA-594 CYP2C8*2 impacts desethylamodiaquine concentration upon repeated artesunate-amodiaquine treatment of uncomplicated malaria in Mali
2023-12-01

<h3>Background</h3> CYP2C8 polymorphisms can impair the metabolism of the antimalarial amodiaquine and influence exposure to the key active metabolite desethylamodiaquine (DEAQ). CYP2C8*2 entailed to slow metabolism phenotype is the most frequent allele in Africa. Here we study the association between CYP2C8*2 carriage and DEAQ D7 drug level for repeated treatments. We conducted a retrospective study on achieved dried blood spot samples and drug level data from West African Network for Clinical Trials of Antimalarial Drugs (WANECAM I) conducted between October 2011 and December 2015 in Bougoula Hameau (Mali). <h3>Methods</h3> We analyzed 206 samples and the related data from patients enrolled in artesunate-amodiaquine arm and actively followed for 2 years. DNA was extracted with QIAGEN kit. CYP2C8*2 status was determined by PCR-RFLP. We used DEAQ day 7 plasma concentration data previously measured by High Performance Liquid Chromatography. The set of outliers with extremely high day 7 DEAQ levels were additionally analyzed by Real time PCR for the presence of CYP2C8*3 and *4. Finally, we analysed the association between homozygous genotype, drug level and the timeframe between episodes. <h3>Results</h3> Out of 206 patients, 153 patients (74.3%), 40 patients (19.4%) and 13 patients (6.3%) patients were respectively *1/*1, *1/*2 and the *2/*2. During the first treatment, there was no difference in D7 DEAQ drug level between the *1/*1 and *2/*2 groups. However, when retreatment was required less than 35 days after the first intervention, a more intense DEAQ accumulation was observed among *2/*2 carriers, relative to the first episode levels (D7, + 67%), compared with *1/*1 subjects (D7, +16%). <h3>Conclusion</h3> We showed that repeated artesunate-amodiaquine administration inside a 35-day post-treatment frame leads to DEAQ accumulation, the effect being significantly higher in patients carrying the reduced function allele CYP2C8*2, suggesting an increased risk of overexposure and amodiaquine toxicity.
PA-184 Lineages diversity and drug resistance of Mycobacterium tuberculosis in Gabon
2023-12-01

<h3>Background</h3> Tuberculosis (TB) is a major public health issue in resource-limited settings, including Gabon, which it is one of the top 30 countries worldwide with a high burden of the disease. Managing multidrug-resistant TB (MDR-TB) in these settings is challenging due to limited access to rapid diagnostics and drug susceptibility testing. Early detection of drug-resistant TB is crucial to controlling transmission of resistant strains and initiating appropriate treatment. The study aimed to determine the proportion and resistance patterns of pre-extensively drug-resistant (Pre-XDR) and extensively drug-resistant (XDR) TB among MDR-TB patients in Gabon and to identify the distribution of their lineages. <h3>Methods</h3> In this cross-sectional study, we collected 92 TB isolates from rifampicin-resistant (RR) patients based on Genexpert. We performed BD MGIT liquid culture and whole-genome sequencing using the MinION according to standard procedures. <h3>Results</h3> Our findings showed that the HIV-TB co-infection rate was 14.1%, and the mean age of the participants was 31.94 years. We observed that 65.2% of patients had MDR-TB, 19.6% had Pre-XDR, 14.1% had RR-TB, and 1.1% had XDR-TB. We identified three main lineages, with Lineage 4 being the most common (81.52%), followed by Lineage 5 (14.13%) and Lineage 2 (3.26%). The dominant genotypes were Cameroon, LAM, Harleem, West Africa 1b, and Beijing, accounting for 47.82%, 19.56%, 17.39%, 6.5%, and 4.3% of cases, respectively. <h3>Conclusion</h3> Our study reveals a high proportion of Pre-XDR patients, underscoring the need to enhance laboratory capacities to monitor Pre-XDR and XDR-TB patients. This is the first detection of Lineage 2, the most virulent TB strain in Gabon, Further studies are needed to investigate the transmission dynamics of the Lineage 2 TB strain in Gabon. TB programs should prioritize the effective and rational use of second-line drugs for newly diagnosed MDR-TB patients to prevent the emergence of Pre-XDR/XDR-TB strains.
PA-452 Molecular surveillance for polymorphisms associated with artemisinin-based combination therapy resistance in plasmodium falciparum isolates from southern Brazzaville and beyond in the Republic of Congo
2023-12-01

<h3>Background</h3> Emergence and spread of P.falciparum strains resistant to artemisinin-based combination therapies (ACTs), poses a significant threat to global malaria control efforts. Therefore, the close monitoring of molecular markers is essential as an early warning system to detect the emergence and spread of resistance. This study aims to assess the prevalence of haplotypes of the Pfcrt, Pfmdr1 and PfK13 resistance markers in isolates from the south of Brazzaville and beyond, in the Republic of Congo. <h3>Methods</h3> Between March and October 2021, a cross-sectional study was conducted in rural and urban areas of the south of Brazzaville and beyond in individuals aged 1–83 years with microscopic P. falciparum infection. Parasite DNA was extracted using Qiagen kit and all samples were screened to confirm P. falciparum infection by nested PCR. Restriction Fragment Length Polymorphism was used for the detection of single nucleotide mutation within the Pfcrt, Pfmdr1 genes of the parasite, and detected mutations were further confirmed using Oxford nanopore sequencing platform, while PfK13 gene mutations were investigated by sequencing. <h3>Results</h3> Among 329 samples with confirmed P. falciparum infection, the overall prevalence of the 76T (Pfcrt), 86Y (Pfmdr1) and 184F (Pfmdr1) mutations were 26.7%, 5.3% and 23.9% respectively. The Pfk13 wild type was found in 98.3% isolates while, 1.7% isolates had a mutation in the Pfk13 domain (4 synonymous mutations and 1 non-synonymous mutation, A578S). No significant difference was observed between rural and urban data. <h3>Conclusion</h3> These results indicate low prevalence of mutations within the Pfcrt, Pfmdr1 genes of P. falciparum and no validated Pfk13 mutation associated with artemisinin drug resistance in this study setting, suggesting that ACTs remain effective in the area, but required continuous surveillance.
PA-376 Saliva as a tool for SARS-CoV-2 genomic and immunological surveillance in the Republic of Congo
2023-12-01

<h3>Background</h3> The design of this study was intended to evaluate the use of saliva as a reliable non-invasive tool for the genomic and immunological surveillance of SARS-CoV-2 infection in the Republic of Congo. <h3>Methods</h3> During this cross-sectional study, the active infection was determined by detecting SARS-CoV-2 RNA using RT-PCR in 220 paired saliva and oropharyngeal samples (OPS), and by sequencing SARS-CoV-2 genome using the Oxford nanopore technology. The detection of anti-SARS-CoV-2 IgG antibody was done in 148 pair saliva and plasma samples using an in-house developed ELISA, and the reproductivity of the assay based on Saliva were assessed in two independent laboratories. <h3>Results</h3> Overall, saliva (22/220) and OPS (23/220) showed similar rates of viral detection (p= 1.00). The sensitivity and specificity of detecting SARS-COV-2 active infection in saliva were 95.7% (95%CI: 79.0–99.8%) and 100% (95%CI: 98.1–100%) respectively, with the mean cycle threshold values similar to those of oropharyngeal samples (p&gt;0.05). The genome sequencing revealed a mean coverage of 95.5 ± 2.8%, finding omicron as the main variant. The anti-SARS-COV-2 antibody detection in saliva showed a sensitivity of 92.0% (95%CI: 85.0–96.0%) and specificity of 93.3% (95%CI: 78.0–99.2%) compared to plasma. There was a high agreement in antibody detection results between FCRM and ITM laboratories (Cohen's kappa 0,94; p = 0.0001). <h3>Conclusion</h3> These findings demonstrate that saliva can be used as a surrogate to Oropharyngeal or plasma for surveillance of SARS-COV-2 infection in the Republic of Congo.
PA-285 Plasmodium falciparum antimalarial drug resistance: population-based spatio-temporal evolutionary trends in Uganda
2023-12-01

<h3>Background</h3> Antimalarial drug resistance threatens global malaria control efforts. Critical resistance-mediating mutations include those in the targets for sulfadoxine-pyrimethamine, transporter proteins and propeller domain of P. falciparum Kelch-13 protein that are associated with artemisinin partial resistance. <h3>Methods</h3> To gain insight into antimalarial drug resistance trends, we surveyed vital P. falciparum polymorphisms from 10–16 health facilities across Uganda from 2016–22. We further assessed for evidence of evolutionary selection of resistant isolates by evaluating diversity in genomic regions flanking resistance loci. <h3>Results</h3> Five mutations in the targets of sulfadoxine (PfDHPS 437G, 540E) and pyrimethamine (PfDHFR 51I, 59R, 108N) were prevalent (80–100%). The prevalence of PfDHFR 164L and PfDHPS 581G mutations, which mediate higher level antifolate resistance, varied between sites and over time. The PfDHFR 164L mutation was most common in southwestern and central Uganda (&gt;20–75%), with increasing prevalences from 2016–17 to 2022, and increases were also seen in other parts of the country. The PfDHPS 581G mutation was also most common in the four sites in southwestern and central Uganda, although significant changes were not detected. Mutations in PfCRT and PfMDR1, associated with aminoquinoline resistance, were increasingly uncommon. The PfCRT 76T allele was detected in western Uganda bordering the Democratic Republic of Congo. The PfMDR1 86Y mutation, which was previously very common, was absent from 2018–2022. The 1246D mutation decreased, with 0% prevalence in 2022. Four PfK13 mutations (675V, 469Y, 469F and 561H), remain highly prevalent by 2022, compared to our earlier reports. Regarding evolutionary selection, isolates with antifolate and aminoquinoline resistance-associated alleles showed similar diversity to wild-type isolates, in genomic regions flanking the resistance loci. <h3>Conclusion</h3> These results suggest limited evidence of recent selection of antifolate resistance, consistent with stable transmission of resistant isolates; and continued recovery of aminoquinoline sensitivity in Uganda.
PA-771 An economic evaluation of a test-and-treat strategy for schistosomiasis control in pregnant women and young children (freeBILy)
2023-12-01

<h3>Background</h3> There exists a remarkable knowledge gap on the effectiveness of schistosomiasis control interventions for pregnant women and children below 5 years of age, resulting in a lack of public health policies and initiatives targeted to these vulnerable groups. We address this gap with the freeBILy trial in Madagascar, which evaluates a test-and-treat strategy (POC-CCA testing and PZQ treatment) in pregnant women and their young children against the status quo. <h3>Methods</h3> We model the cost-effectiveness of the strategy in comparison to three alternatives: PZQ treatment after a Kato-Katz positive result, presumptive treatment if symptomatic, and preventive chemotherapy. We develop separate models for pregnant women and their young children, which include deterministic and probabilistic sensitivity analyses. Notably, in the model for pregnant women, we employ health-related quality of life (HRQoL) as a metric to represent the health outcomes of the compared strategies. HRQoL was derived from the administration of EQ-5D-3L questionnaire to 500 pregnant women enrolled in two trial training sites at four time points, twice before and twice after giving birth. While this data will not be considered for the estimate of intervention effectiveness, it provides invaluable information for the economic evaluation. HRQoL was also estimated alongside Gabon freeBILy trial among 630 pregnant women and used in the sensitivity analysis. <h3>Results</h3> Preliminary results point to a potential increase in HRQoL in the intervention group (POC-CCA testing and PZQ treatment) in comparison to the control group in Madagascar. However, these results will have to be validated against trial effectiveness measures. In addition, the final cost estimates of the compared strategies will determine the cost-effectiveness of the evaluated strategy. <h3>Conclusion</h3> The results will inform policy about which strategy to prioritize given resource constraints in Madagascar and similar settings. Funding: EDCTP, RIA2016MC1626
PA-367 Profile of molecular markers of Plasmodium falciparum resistance to Sulfadoxine-Pyrimethamine in southern Brazzaville and beyond, in the Republic of Congo
2023-12-01

<h3>Background</h3> Growing resistance of Plasmodium falciparum to Sulfadoxine-Pyrimethamine threatens the effectiveness of the intermittent preventive treatment during pregnancy with Sulfadoxine-Pyrimethamine (IPTp-SP) in malaria endemic areas. WHO recommends discontinuation in case of ineffectiveness as determined by over 95% and 10% prevalence of K540E and A581G mutants respectively. The objective of this study was to determine the prevalence of molecular markers of P.falciparum resistance to SP in the parasite population circulating in the south of Brazzaville and beyond, in the Republic of Congo. <h3>Methods</h3> Two parallel surveys including hospital and community based cross sectional studies were carried out in the south of Brazzaville and beyond (urban, rural areas) between February 2021 and September 2022, to characterize the molecular markers of P.falciparum resistance to SP (dhfr and dhps). Restriction Fragment Length Polymorphism was used for the detection of single nucleotide mutation within the dhfr and dhps genes of the parasite, and detected mutations were further confirmed using Oxford nanopore sequencing platform. <h3>Results</h3> High prevalence of mutations was reported for dhfr gene: N51I (100%), C59R (79.9%), S108N (100%), N164L (0.9%), and dhps gene: A437G (89.5%), K540E (42.4%), A581G (42.1%). The prevalence of the quintuple mutant (N51I+ C59R + S108N + A437G + K540E) and sextuple mutant (N51I+ C59R + S108N + A437G + K540E + A581G) were reported for 32.9% (111/337) and 20.8% (70/337) of the participants respectively while all the seven investigated mutations were reported in only one participant (0.3%). dhfr and dhps mutations were more prevalent in rural compared to the urban areas. <h3>Conclusion</h3> These results indicate high prevalence of mutations within the dhfr and dhps genes of P. falciparum in south of Brazzaville and beyond in the Republic of Congo, which might threaten the effectiveness of IPT-SP in this area.
PA-507 Genomic surveillance of infectious pathogens in the Republic of Congo
2023-12-01

<h3>Background</h3> Deadly emerging infectious pathogens pose an unprecedented challenge to health systems worldwide, especially in the Republic of Congo, where health care infrastructure is limited. Thus the COVID-19 pandemic has been an opportunity to improve the national genomic platform that could be expand to all circulating pathogens serving surveillance, prevention and response actions. This work aimed to establish the genomic platform for the effective control of infectious pathogens in the Republic of Congo. <h3>Methods</h3> By 2021, we established the Oxford Nanopore Technology platform for the first time in the Republic of Congo to respond firstly to the COVID-19 pandemic and secondly to other pathogens like Plasmodium falciparum, Mycobacterium tuberculosis, HIV and others. Between April 2020 and August 2022, a total of 1200 oropharyngeal samples were tested positive for SARS-CoV-2 by RT-PCR. Of these samples, 589 with Ct&lt; 28 were selected for sequencing by ONT next generation sequencing (NGS). All the complete sequenced genomes were submitted on GISAID for publication, and variants were identified using Pangolin and Nextclade nomenclature. <h3>Results</h3> A total of 381 SARS-CoV-2 whole genomes were successfully sequenced and submitted on GISAID. Our results revealed the circulation of 21 SARS-CoV-2 variants in the Republic of Congo during the study period, with the presence of variants of concern such as alpha (B.1.1.7), delta (B.1.617.2) and Omicron (B.1.1.519). Four waves of the virus epidemics were observed during this study period. The B.1.640.1 variant was reported for the first time in the Republic of Congo through this study, and was observed to be spreading locally and regionally. <h3>Conclusion</h3> This work contributed to monitor in a daily basis the spread of SARS-CoV-2 in the country to support the national containment strategies of the pandemic. This established platform is serving for the identification of other pathogens that could represent a threat of public health.
PA-562 Epidemiology of HIV and Helminth co-infection among pulmonary tuberculosis patients at Jamot hospital in Yaoundé, Cameroon
2023-12-01

<h3>Background</h3> Tuberculosis (TB), HIV and Helminths are serious overlapping public health problems in sub-Saharan Africa. This triple burden may lead to accelerated disease progression. Although HIV is integrated in TB programs in Cameroon, data on TB-helminth co-infection still remains limited. This study was aimed at determining the prevalence of helminths and their associated factors among pulmonary tuberculosis patients at Jamot hospital in Yaoundé, Cameroon. <h3>Methods</h3> This was a cross sectional study conducted at the Jamot hospital in Yaoundé, Cameroon from April 2022 to March 2023 with participants aged 18 years and above. A well designed questionnaire was used to capture sociodemographic data, clinical history and risk factors for TB, HIV and helminth infections. Sputum, stool and blood samples were collected from each consenting participant. Sputum was examined using auramine microscopy. Stool was examined using the kato-katz and Mini-FLOTAC techniques. Blood was used for HIV serology according to guidelines. TB-uninfected healthy controls were also recruited and their blood and stool samples similarly analysed. <h3>Results</h3> A total of 321 sputum smear-positive TB patients (72% males and 28% females) and 65 healthy controls (54% males and 46% females) were included in this study. The prevalence of TB-HIV co-infection was 13.4% (43/321). The prevalence of any helminth infection among TB patients was 13.5% (37/274) and 7.7% (5/65) among controls. The most prevalent helminth species in this study was Ascaris lumbricoides (62%, 23/37), followed by Trichuris trichuria (19%, 7/37), Strongyloides stercoralis (5.4%, 2/37), and hookworm (2,7%, 1/37). TB-HIV-Helminth triple co-infection was found in 3 cases. <h3>Conclusion</h3> The prevalence of TB-HIV and TB-Helminth co-infection is similar. This emphasizes the fact that diagnosis and treatment of helminth infections should be integrated in TB control programs in Cameroon for a better management of the disease.
Assets for "Simulation-Based Inference of Surface Accumulation and Basal Melt Rates of an Antarctic Ice shelf from Isochronal Layers"
2023-12-01

Experimental data reported in "Simulation-Based Inference of Surface Accumulation and Basal Melt Rates of an Antarctic Ice shelf from Isochronal Layers". Contains processed simulation data for both synthetic and Ekström Ice Shelf experiments. Selected best layers for each Internal Radar Horizons in the respective simulated datasets are contained in "all_layers_final.p", and the respective mass balance parameters for those simulations in "all_mbs_final.p". Trained Neural Posterior Estimator (NPE) models for each IRH are found in "inference.p" files, and posterior predictive simulations in "post_predictive.p" files for each posterior respectively. Code to visualise and plot this data is found in https://github.com/mackelab/sbi-ice.
Figurations of Returning to the Community in Léonora Miano’s African Novels
2023-12-01

Abstract This article examines figurations of returning to the community in two of Léonora Miano’s novels. These novels offer an opportunity to broaden the notion of returning to community that, in philosophical debates, tends to be essentialist and abstract. In Les aubes écarlates and La saison de l’ombre, two clans find themselves confronted with the abduction of community members who become child soldiers or slaves. The physical or spiritual return of those abductees to their communities is at the core of the novels, and it is closely linked to questions of memory. Understanding the dynamics of return as a figuration—both in the literary sense and in Norbert Elias’s process sociology sense—helps us look at the concrete interactions that make up a community. This article analyzes the physical, mnemonic, and spiritual dimensions of returning to community and looks at the significance of inventing new rituals and forms of community.
Recent progress in quantitative phosphoproteomics
2023-12-02

Despite quantitative phosphoproteomics is one of the most thriving fields in the proteomics world, many challenges still have to be overcome to facilitate even deeper and more comprehensive analyses as required in the current research, especially at single cell levels and in clinical diagnostics.