HIV subtype and drug resistance patterns among drug naïve persons in Jos, Nigeria

To determine HIV-1 subtypes and antiretroviral drug resistance mutations for 16 infected, pregnant women in Jos, Nigeria, part of pol (1040 bp) was amplified from patient PBMC DNA, sequenced andanalyzed. Eight of the samples were subtype G, three were CRF02_AG and 2 were unique recombinant forms (URF) between G and CRF02_AG. The remaining consisted of 3 different strains: one was subtypeC, and the other 2 were unrelated URF. Nearly full-length genome sequences were completed for 6 of the strains: 4 subtype G and 2 CRF02_AG. In the 14 drug-naïve subjects, no primary resistance-associated mutations were found, but secondary mutations were identified in 7 different codons of the gene coding for protease: PR K20I, M36I, L63A/P/V, V82I, L10M/I and I93L. In addition, the K238R mutation was identified in the reverse transcriptase gene of 3 viruses. The PR K20I and M36I mutations occurred in all of the strains, and the L10M and V82I mutations occurred only in subtype G. The mutation, I93L, was carried by subtype C viruses. Two of the women that had prior niverapine treatment, had primary resistance-associated mutations, RT M184V and K103N, archived in their proviral DNA several months after treatment cessation. The study reports a predominance of clade G and CRF02_AG, and provides many more examples of nearly full-length genome sequences for subtype G viruses from Nigeria. The ubiquitous presence of PI secondary resistance-associated mutations, as well as primary resistanceassociatedmutations in 2 previously treated women, underscores the need to ensure adherence compliance to treatment

Validation of xMAP SARS-CoV-2 Multi-Antigen IgG assay in Nigeria

Objective: There is a need for reliable serological assays to determine accurate estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. Most single target antigen assays have shown some limitations in Africa. To assess the performance of a multi-antigen assay, we evaluated a commercially available SARS-CoV-2 Multi-Antigen IgG assay for human coronavirus disease 2019 (COVID-19) in Nigeria. / Methods: Validation of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was carried out using well-characterized SARS-CoV-2 reverse transcription polymerase chain reactive positive (97) and pre-COVID-19 pandemic (86) plasma panels. Cross-reactivity was assessed using pre-COVID-19 pandemic plasma specimens (213) from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). / Results: The overall sensitivity of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was 75.3% [95% CI: 65.8%– 82.8%] and specificity was 99.0% [95% CI: 96.8%– 99.7%]. The sensitivity estimate increased to 83.3% [95% CI: 70.4%– 91.3%] for specimens >14 days post-confirmation of diagnosis. However, using the NAIIS pre-pandemic specimens, the false positivity rate was 1.4% (3/213). / Conclusions: Our results showed overall lower sensitivity and a comparable specificity with the manufacturer’s validation. There appears to be less cross-reactivity with NAIIS pre-pandemic COVID-19 specimens using the xMAP SARS-CoV-2 Multi-Antigen IgG assay. In-country SARS-CoV-2 serology assay validation can help guide the best choice of assays in Africa

Intestinal Microbiota Shifts towards Elevated Commensal Escherichia coli Loads Abrogate Colonization Resistance against Campylobacter jejuni in Mice

Background: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. Methodology/Principal Findings: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. Conclusion/Significance: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiot

Mortality of drug-resistant tuberculosis in high-burden countries: comparison of routine drug susceptibility testing with whole-genome sequencing

Background: Drug-resistance threatens global tuberculosis control. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS). Methods: We collected pulmonary Mycobacterium tuberculosis isolates and clinical data from adult tuberculosis patients from Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and drug resistance, from 2013 to 2016. Sites tested drug susceptibility using routinely available methods. WGS was done on Illumina HiSeq 2500 in the USA and Switzerland, and TBprofiler used to analyse the genomes. We analysed mortality in multivariable logistic regression models adjusted for sex, age, HIV-status, history of tuberculosis, and sputum positivity. Findings: We included 582 tuberculosis patients. The median age was 33 years (interquartile range 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan- susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR). The local results were discordant with the WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with a high agreement. Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inappropriate treatment according to WGS results and the World Health Organization (WHO) treatment guidelines. The analysis of mortality was based on 530 patients; 63 (12%) died, and 77 patients (15%) received inappropriate treatment. Mortality ranged from 6% in patients with pan-susceptible tuberculosis (18/310) to 39% in patients with pre-XDR/XDR tuberculosis (9/23). The adjusted odds ratio for mortality was 4.92 (95% CI 2.47-9.78) among under-treated patients, compared to appropriately treated cases. Interpretation: In seven high-burden tuberculosis countries, we observed discrepancies between drug resistance patterns obtained locally and WGS. The under-diagnosis of drug resistances resulted in inappropriate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information required to improve the outcomes of drug-resistant tuberculosis in high-burden settings. Our results support the WHO's call for point-of- care tests based on WGS