Gut microbiota in vaccine naïve Gabonese children with rotavirus A gastroenteritis.

Background: While the gut microbiome modulates the pathogenesis of enteric viruses, how infections caused by rotavirus A (RVA), with or without diarrhoea, alter the gut microbiota has been sparsely studied. Methods: From a cohort of 224 vaccine naïve Gabonese children with and without diarrhoea (n = 177 and n = 67, respectively), 48 stool samples were analysed: (i) RVA with diarrhoea (n = 12); (ii) RVA without diarrhoea (n = 12); (iii) diarrhoea without RVA (n = 12); (iv) healthy controls without diarrhoea and RVA (n = 12). The 16S rRNA metabarcoding using Oxford Nanopore sequencing data was analysed for taxonomic composition, abundance, alpha and beta diversity, and metabolic pathways. Findings: Alpha diversity showed that children with acute diarrhoea (with and without RVA infection), and children with acute diarrhoea without RVA had low microbial diversity compared to healthy children (p = 0.001 and p = 0.006, respectively). No significant differences observed when comparing children with RVA with or without diarrhoea. Beta diversity revealed high microbial heterogeneity in children without diarrhoea. Proteobacteria (68%) and Firmicutes (69%) were most common in the diarrhoea and non-diarrhoea groups, respectively. Proteobacteria (53%) were most common in children without RVA, while Firmicutes (55%) were most common with RVA. At the genus level, Escherichia (21%), Klebsiella (10%) and Salmonella (4%) were abundant in children with diarrhoea, while Blautia (11%), Clostridium (8%), Lachnoclostridium (6%) and Ruminococcus (5%) were abundant in children without diarrhoea. Metabolites involved in amino acid, carbohydrate, lipid, nucleotide, and vitamin metabolism were quantitatively altered. Interpretation: Although host physiology dictates the intestinal milieu, diarrhoea per se can alter a balanced gut microbiota, whereas infectious diarrhoea disrupts the gut microbiome and reduces its diversity.

Whole genome sequencing and phylogenetic analysis of SARS-CoV-2 strains isolated during the COVID-19 pandemic in Nigeria.

Objectives: The emergence and spread of SARS-CoV-2 have stimulated ongoing research into the virus transmission dynamics, circulating variants, and potential mutations. This study was conducted to understand the genomic dynamics of the epidemic in Nigeria. Design: Whole genome sequencing was conducted on SARS-CoV-2 samples collected during the first and second outbreaks using the Oxford Nanopore MinION sequencing platform. Phylogenetic analysis was conducted, and genomes were grouped into different pangolin lineages. Results: The study revealed four circulating SARS-CoV-2 variants. The Alpha (B.1.1.7) variant was the most prevalent (32.7%), followed by Beta (B.1 B.1.1, L.3, and B.1.1.318) (30.8%), Eta (B.1.525) (28.9%), and Delta (B.1.617, AY.1, AY.109, and AY.36) (7.7%). Phylogenetic analysis revealed three clusters with four Nextstrain clades (20I, 20B, 21D, and 21J). The Alpha lineages (B.1.1.7) clustered with references from Italy. The Beta lineages (Clade 20B) (B.11, B.11318, and L3) and sub-lineage B.11 were distinct. Sub-lineage B.11318 is clustered with references from the USA, whereas sub-lineage L3 is clustered with references from Russia, the Philippines, Australia, and Japan. The 21D and 21J, belonging to two Pango lineages, Eta (B.1525) and Delta (B.1.617 and AY.109), showed high genetic similarity. Conclusion: The phylogenetic relatedness of the lineages suggests multiple virus introduction, which could be a source of more virulent, locally adapted variants.

Tübingen model study: large-scale introduction of rapid antigen testing in the population and the viral dynamics of SARS-CoV-2.

Despite of contact restrictions, population mobility remains the main reason for the spread of SARS-CoV-2. The state of Baden-Württemberg (BW), Germany, approved a model study in Tübingen (TÜMOD) to evaluate how mandatory rapid diagnostic tests (RDT) could reduce transmission. Between 16 March and 24 April 2021, approximately 165,000 residents and visitors to the city were screened for SARS CoV-2 infection using Abbott Panbio™ COVID-19 Antigen rapid test device. We assessed incidences and recorded epidemiological characteristics in a subset of 4,118 participants recruited at three of the nine testing stations. PCR tests were performed in RDT-positives to determine the positive predictive value (PPV), and circulating variants of SARS-CoV-2 were identified by whole-genome sequencing. 2,282 RDT-negative samples were tested by pooled PCR to calculate the false negative rate (FNR). Viral load was compared between variants. 116 (3%) participants were positive by RDT, and of these, 57 (49%) were positive by PCR, 55 (47%) were negative. This resulted in a PPV of 51%. Of the 57 positives, 52 SARS-CoV-2 genomes were successfully sequenced. Of these, 50 belonged to the B.1.1.7 lineage, which had a high viral load (average Ct = 19). Of the 2,282 RDT negatives tested, all were PCR negative (FNR 0%). At the end of TÜMOD, the incidence in Tübingen, which was initially lower, had reached the incidence in the state of BW. While it is difficult to assess the impact of TÜMOD on incidence independent of confounding factors, further studies are needed to identify the effect of close-meshed testing on infection rates.

Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. MATERIALS AND METHODS: We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2-∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. RESULTS: Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. CONCLUSION: The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes.

Diagnosis of pathogens causing bacterial meningitis using Nanopore sequencing in a resource-limited setting.

AIM: The aim of the present study is to compare the performance of 16S rRNA Nanopore sequencing and conventional culture in detecting infectious pathogens in patients with suspected meningitis in a resource-limited setting without extensive bioinformatics expertise. METHODS: DNA was isolated from the cerebrospinal fluid (CSF) of 30 patients with suspected bacterial meningitis. The isolated DNA was subjected to 16S sequencing using MinION™. The data were analysed in real time via the EPI2ME cloud platform. The Nanopore sequencing was done in parallel to routine microbiological diagnostics. RESULTS: Nanopore sequencing detected bacterial pathogens to species level in 13 of 30 (43%) samples. CSF culture showed 40% (12/30) positivity. In 21 of 30 patients (70%) with suspected bacterial meningitis, both methods yielded concordant results. About nine of 30 samples showed discordant results, of these five were false positive and four were false negative. In five of the culture negative results, nanopore sequencing was able to detect pathogen genome, due to the higher sensitivity of the molecular diagnostics. In two other samples, the CSF culture revealed Cryptococcus neoformans and Streptococcus pneumoniae, which were not detected by Nanopore sequencing. Overall, using both the cultures and 16S Nanopore sequencing, positivity rate increased from 40% (12/30) to 57% (17/30). CONCLUSION: Next-generation sequencing could detect pathogens within six hours and could become an important tool for both pathogen screening and surveillance in low- and middle-income countries (LMICs) that do not have direct access to extensive bioinformatics expertise.

Host genetic loci LZTFL1 and CCL2 associated with SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: Host genetic factors contribute to the variable severity of COVID-19. We examined genetic variants from genome-wide association studies and candidate gene association studies in a cohort of patients with COVID-19 and investigated the role of early SARS-CoV-2 strains in COVID-19 severity. METHODS: This case-control study included 123 COVID-19 cases (hospitalized or ambulatory) and healthy controls from the state of Baden-Wuerttemberg, Germany. We genotyped 30 single nucleotide polymorphisms, using a custom-designed panel. Cases were also compared with the 1000 genomes project. Polygenic risk scores were constructed. SARS-CoV-2 genomes from 26 patients with COVID-19 were sequenced and compared between ambulatory and hospitalized cases, and phylogeny was reconstructed. RESULTS: Eight variants reached nominal significance and two were significantly associated with at least one of the phenotypes "susceptibility to infection", "hospitalization", or "severity": rs73064425 in LZTFL1 (hospitalization and severity, P <0.001) and rs1024611 near CCL2 (susceptibility, including 1000 genomes project, P = 0.001). The polygenic risk score could predict hospitalization. Most (23/26, 89%) of the SARS-CoV-2 genomes were classified as B.1 lineage. No associations of SARS-CoV-2 mutations or lineages with severity were observed. CONCLUSION: These host genetic markers provide insights into pathogenesis and enable risk classification. Variants which reached nominal significance should be included in larger studies.

SARS-CoV-2 B.1.214.1, B.1.214.2 and B.1.620 are predominant lineages between December 2020 and July 2021 in the Republic of Congo.

Background: : SARS-CoV-2 variants have been emerging and are shown to increase transmissibility, pathogenicity, and decreased vaccine efficacies. The objective of this study was to determine the distribution, prevalence, and dynamics of SARS-CoV-2 variants circulating in Brazzaville, the Republic of Congo (ROC). Methods: : Between December 2020 and July 2021, a total of n=600 oropharyngeal specimens collected in the community were tested for COVID-19. Of the samples tested, 317 (53%) were SARS-CoV-2 positive. All samples that had a threshold of Ct <30 (n=182) were sequenced by next-generation sequencing (NGS), and all complete sequenced genomes were submitted to GISAID; lineages were assigned using pangolin nomenclature and a phylogenetic tree was reconstructed. In addition, the global prevalence of the predominant lineages was analysed using data from GISAID and Outbreak databases. Results: : A total of 15 lineages circulated with B.1.214.2 (26%), B.1.214.1 (19%) and B.1.620 (18%) being predominant. The variants of concern (VOC) alpha (B.1.1.7) (6%) and for the first time in June delta (B.1.617.2) (4%) were observed. In addition, the B.1.214.1 lineage first reported from ROC was observed to be spreading locally and regionally. Phylogenetic analysis suggests that the B.1.620 variant (VUM) under observation may have originated from either Cameroon or the Central African Republic. SARS-CoV-2 lineages were heterogeneous, with the densely populated districts of Poto-Poto and Moungali likely the epicenter of spread. Conclusion: : Longitudinal monitoring and molecular surveillance across time and space are critical to understanding viral phylodynamics, which could have important implications for transmissibility and impact infection prevention and control measures.

SARS-CoV-2 viral dynamics of the first 1000 sequences from Vietnam and neighbouring ASEAN countries.

Objective: The regional distribution and transmissibility of existing COVID-19 variants of concern (VOC) has led to concerns about increasing transmission, given the ability of VOCs to evade immunity as breakthrough infections become more prevalent. Methods: SARS-CoV-2 genomes (n = 277) were sequenced and analysed alongside all available genomes from Vietnam and ASEAN countries to understand the phylodynamics. The observed lineages were assigned using Pangolin nomenclature, and spread patterns were investigated. Results: Between January and November 8, 2021, VOCs, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2), were observed across the ASEAN countries. While alpha and delta were the major VOCs in nine ASEAN countries, delta was predominant. The alpha VOC was first reported by Singapore, beta by Malaysia, gamma by the Philippines, and delta by Singapore. Of the first 1000 genomes analysed from Vietnam, alpha and delta were the most represented, with delta being the dominant VOC from May 2021. The delta variant was introduced in early January 2021, and formed a large cluster within the representative genomes. Conclusion: Spatial and temporal monitoring of SARS-CoV-2 variants is critical to the understanding of viral phylodynamics, and will provide useful guidance to policy makers for infection prevention and control.

Evaluation of SARS-CoV-2 diagnostics and risk factors associated with SARS-CoV-2 infection in Zambia.

OBJECTIVES: To conduct a diagnostic validation study of SARS-CoV-2 diagnostic kits. METHODS: We compared SARS-CoV-2 diagnostic test results from 3 RT-PCR assays used by the Zambian government between November 2020 and February 2021 (Panther Fusion assay, Da An Gene's 2019-nCoV RNA kit and Maccura's PCR Kit) with the Altona RealStar RT-PCR kit which served as the gold standard. We also evaluated results from rapid antigen testing and whether comorbidities were linked with increased odds of infection. RESULTS: We recruited 244 participants, 61% (149/244) were positive by at least 1 PCR assay. Da An Gene, Maccura, and Panther Fusion assays had sensitivities of 0.0% (95% confidence interval [CI] 0%-41%), 27.1% (95% CI 15%-42%), and 76% (95% CI 65%-85%), respectively, but specificity was low (<85% for all 3 assays). HIV and TB were not associated with SARS-CoV-2, whereas female sex (OR 0.5 [0.3-0.9], p = 0.026) and chronic pulmonary disease (0.1 [0.0-0.8], p = 0.031) were associated with lower odds of SARS-CoV-2 infection. Of 44 samples, 84% sequenced were Beta variant. CONCLUSIONS: The RT-PCR assays evaluated did not meet WHO recommended minimum sensitivity of 80%. Local diagnostic validation studies should be embedded within preparedness plans for future outbreaks to improve the public health response.

Association Between Soluble Notch Ligand Delta-like Ligand 1 and Bleeding Complications in Patients With Dengue Fever Infection.

Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay. Seventeen of 115 patients (14.8%) experienced bleeding manifestations. High soluble delta-like ligand 1 (sDLL1) plasma levels was associated with bleeding (median, 15 674 vs 7117 pg/mL; P < .001). Receiver operating characteristic (ROC) curve analysis demonstrated that sDLL1 had the best test performance (area under the ROC curve, 0.852), with 88% sensitivity and 84% specificity. The combination with alanine aminotransferase and aspartate aminotransferase slightly increased sDLL1 performance. sDLL1 may be useful to guide clinical management of patients with patients in endemic settings.

Emergence of B.1.1.318 SARS-CoV-2 viral lineage and high incidence of alpha B.1.1.7 variant of concern in the Republic of Gabon.

OBJECTIVE: Variants of concern (VOCs) associated with relatively high transmissibility appear to be rapidly spreading in Gabon. Therefore, it is imperative to understand the distribution of several VOCs in the population, which could have implications for transmissibility and vaccine efficacy. METHODS: Between February and May 2021, SARS-CoV-2 genomes were sequenced using the Oxford nanopore MinION method and the respective genome diversity was elucidated. Phylogenetic analysis was performed and genomes were classified using pangolin lineages. RESULTS: The results highlighted an increase (46%) in the alpha VOC (B.1.1.7) in the Gabonese population over the study period. In addition, an increase (31%) in the B.1.1.318 lineage, which is associated with high transmission and impaired vaccine efficacy (D614G+E484K+Y144del), was detected. CONCLUSION: With the second wave ongoing, these findings highlight the need for surveillance of the SARS-CoV-2 genome in the Republic of Gabon and should provide useful guidance to policymakers in selecting an appropriate vaccine for this population.

Low Prevalence of HEV Infection and No Associated Risk of HEV Transmission from Mother to Child among Pregnant Women in Vietnam.

Infections with HEV in low- and middle-income countries (LMICs) are associated with increased rates of preterm birth, miscarriage, and stillbirth. The aim of the present study was to investigate HEV infections in pregnant women and the possibility of mother-to-child transmission, and associated outcomes. A total of 183 pregnant women in their third trimester were recruited and followed until delivery. Anti-HEV IgG and IgM were determined via enzyme-linked immunosorbent assay (ELISA), and HEV nucleic acids were detected in stool and cord blood samples. HEV genotypes were identified by Sanger sequencing, and phylogenetic analyses were performed. Mother-to-child transmission and associated adverse outcomes were not observed. Only 2% of patients (n = 4/183) tested positive for anti-HEV IgM, and 8% (n = 14/183) tested positive for anti-HEV IgG antibodies. Cord blood (n = 150) analysis showed that there was no IgM detected, while 4% (n = 6/150) tested positive for anti-HEV IgG, which was consistent with mothers testing positive for anti-HEV IgG. Nucleic acid tests for HEV RNA yielded 2% (n = 4/183) from the serum and stool of pregnant women, and none from cord blood. The HEV isolates belonged to the genotype HEV-3a, with 99% homology with humans and 96% with pigs. No association was found between the risk of HEV infection and pregnancy outcomes or HEV transmission from mother to child. HEV-3 infections of zoonotic origin in pregnancy might have eventually resolved without complications.

Host genetic factors determining COVID-19 susceptibility and severity.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.

How to (ab)use a COVID-19 antigen rapid test with soft drinks?

With reasonably good specificity and sensitivity, the speed and convenience of COVID-19 antigen tests have led to self-testing in schools, offices, and universities in the European Union (EU). Although self-testing can be beneficial and increase the accessibility to testing, there are potential ways to confound a positive COVID-19 lateral flow test. We observed that all soft drinks, energy drinks, alcoholic beverages (vodka, whiskey, and brandy), commercially bottled mineral water, and carbonated mineral water caused the appearance of a red test line. However, when equal volumes of the buffer and the respective beverages are mixed, there are no false-positive test lines. Deceitful methods may easily lead to misuse of COVID-19 antigen rapid tests and lead to false-positive results; however, this does not prove that these tests are unreliable when performed correctly.

Host factors facilitating SARS-CoV-2 virus infection and replication in the lungs.

SARS-CoV-2 is the virus causing the major pandemic facing the world today. Although, SARS-CoV-2 primarily causes lung infection, a variety of symptoms have proven a systemic impact on the body. SARS-CoV-2 has spread in the community quickly infecting humans from all age, ethnicities and gender. However, fatal outcomes have been linked to specific host factors and co-morbidities such as age, hypertension, immuno-deficiencies, chronic lung diseases or metabolic disorders. A major shift in the microbiome of patients suffering of the coronavirus disease 2019 (COVID-19) have also been observed and is linked to a worst outcome of the disease. As many co-morbidities are already known to be associated with a dysbiosis of the microbiome such as hypertension, diabetes and metabolic disorders. Host factors and microbiome changes are believed to be involved as a network in the acquisition of the infection and the development of the diseases. We will review in detail in this manuscript, the immune response toward SARS-CoV-2 infection as well as the host factors involved in the facilitation and worsening of the infection. We will also address the impact of COVID-19 on the host's microbiome and secondary infection which also worsen the disease.

Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients.

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.

Maternal Vaginal Colonization and Extended-Spectrum Beta-Lactamase-Producing Bacteria in Vietnamese Pregnant Women.

Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) resistance to commonly prescribed drugs is increasing in Vietnam. During pregnancy, ESBL-E may predispose women to reproductive tract infections and increases the risk for neonatal morbidity. Vaginal colonization and infections by Escherichia coli and Klebsiella pneumoniae are seldom studied in Vietnam. In this study, we investigated ESBL-producing Enterobacterales in the birth canal of pregnant women. Between 2016 and 2020, vaginal swabs were collected from 3104 pregnant women (mean gestational age of 31 weeks) and inoculated onto MacConkey agar plates. Colonies were subjected to direct identification and antimicrobial susceptibility testing using the VITEK®-2 automated compact system and disk diffusion. ESBL production was determined phenotypically. E. coli, Klebsiella species were identified in 30% (918/3104) of the vaginal swabs, with E. coli being the most common (73%; 667/918). ESBL-production was detected in 47% (432/918) of Enterobacterales, with frequent multidrug-resistant phenotype. The overall prevalence of carbapenem resistance was low (8%). Over 20% of Klebsiella spp. were carbapenem-resistant. Pregnant women had a high prevalence of colonization and may transmit ESBL-E to neonates at birth, an important risk factor to be considered. The high rate of ESBL-producers and carbapenem resistance in Enterobacterales in Vietnam emphasizes the need for consequent surveillance and access to molecular typing.

Diagnosis of Chikungunya Virus in Febrile Patients From a Malaria Holoendemic Area.

INTRODUCTION: Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls. METHODS: Between June and November 2019, a total of 107 febrile patients with suspected CHIK were subjected to differential diagnosis both for CHIK and malaria. Patients were screened for CHIK virus using molecular diagnosis by real-time PCR, serologic testing by IgM-specific and IgG-specific ELISAs, and lateral flow-based method with rapid diagnostic test (RDT), while malaria diagnosis was confirmed by PCR methods. Pro-inflammatory (IL-12, IL-16, IFN-γ, TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were quantified in patients and healthy controls by ELISA assays. RESULTS: Molecular diagnoses revealed that 57% (61/107) were positive for CHIK by RT-PCR, while serologic testing revealed 31% (33/107) and 9% (10/107) seropositivity for anti- IgM and IgG, respectively. None of the patients were CHIK RDT-positive. Also, 27% (29/107) were PCR-positive for malaria. Among the malaria-positive patients, 14% (15/107) were co-infected with CHIK and 13% (14/107) were monoinfection. Plasma IL-12 and TNF-α levels were increased in patients with malaria and IL-13 levels were increased in patients with co-infection (p<0.05). CONCLUSION: Co-infection of malaria and CHIK were common in febrile Congolese patients. Real-time PCR was a better tool for detecting actual occurrences of CHIK in a malaria holoendemic area.

Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression.

The inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case-control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.