Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial.

BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per µL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING: ANRS MIE.

Reported antibiotic use among patients in the multicenter ANDEMIA infectious diseases surveillance study in sub-saharan Africa.

BACKGROUND: Exposure to antibiotics has been shown to be one of the drivers of antimicrobial resistance (AMR) and is critical to address when planning and implementing strategies for combatting AMR. However, data on antibiotic use in sub-Saharan Africa are still limited. Using hospital-based surveillance data from the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA), we assessed self-reported antibiotic use in multiple sub-Saharan African countries. METHODS: ANDEMIA included 12 urban and rural health facilities in Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo, and Republic of South Africa. Patients with acute respiratory infection (RTI), acute gastrointestinal infection (GI) and acute febrile disease of unknown cause (AFDUC) were routinely enrolled, and clinical, demographic, socio-economic and behavioral data were collected using standardized questionnaires. An analysis of ANDEMIA data from February 2018 to May 2022 was conducted. Reported antibiotic use in the ten days prior to study enrolment were described by substance and by the WHO AWaRe classification ("Access", "Watch", "Reserve", and "Not recommended" antibiotics). Frequency of antibiotic use was stratified by location, disease syndrome and individual patient factors. RESULTS: Among 19,700 ANDEMIA patients, 7,258 (36.8%) reported antibiotic use. A total of 9,695 antibiotics were reported, including 54.7% (n = 5,299) from the WHO Access antibiotic group and 44.7% (n = 4,330) from the WHO Watch antibiotic group. The Watch antibiotic ceftriaxone was the most commonly reported antibiotic (n = 3,071, 31.7%). Watch antibiotic use ranged from 17.4% (56/322) among RTI patients in Côte d'Ivoire urban facilities to 73.7% (630/855) among AFDUC patients in Burkina Faso urban facilities. Reported antibiotic use included WHO Not recommended antibiotics but no Reserve antibiotics. CONCLUSIONS: Reported antibiotic use data from this multicenter study in sub-Saharan Africa revealed a high proportion of WHO Watch antibiotics. Differences in Watch antibiotic use were found by disease syndrome, country and health facility location, which calls for a more differentiated approach to antibiotic use interventions including further evaluation of accessibility and affordability of patient treatment.

On-site evaluation as external quality assessment of microbiology laboratories involved in sentinel laboratory-based antimicrobial resistance surveillance network in Burkina Faso.

BACKGROUND: The laboratory-based surveillance of antimicrobial resistance (AMR) is a priority component of the multisectoral national action plan to combat AMR in Burkina Faso. This study aimed to assess the QMS of microbiology laboratories involved in the Sentinel laboratory-based antimicrobial resistance surveillance network in Burkina Faso. METHODS: A cross-sectional study was conducted from September 1st to November 30th, 2022. The external quality assessment (EQA) method used was on-site evaluation using a checklist that was developed and validated by a technical committee of experts. Teams of two, including an antimicrobial susceptibility test (AST) specialist and a QMS specialist, were trained on this checklist to conduct the assessment. Satisfactory performance was defined as any on-site evaluation score 80% and above with the aim of developing action plans to address gaps. RESULTS: All 18 laboratories were evaluated. The overall average performance score of the participating laboratories was 40%. The highest overall performance score was 58%, and the lowest overall performance score was 26%. The average overall scores were not significantly different between private and public laboratories (p value = 0.78). The only section of the checklist with the satisfactory performance concerned the "Analytical step of AST", with 76.5% (13/17) of the sentinel laboratories having a score ≥ 80%. CONCLUSION: The performance of the QMS of the sentinel laboratories in Burkina Faso for AMR surveillance was unsatisfactory, and a corrective action plan was proposed to support these laboratories in improving their QMS over the next 3 years.

An emerging clade of Chikungunya West African genotype discovered in real-time during 2023 outbreak in Senegal.

Chikungunya (CHIKV) is a re-emerging endemic arbovirus in West Africa. Since July 2023, Senegal and Burkina Faso have been experiencing an ongoing outbreak, with over 300 confirmed cases detected so far in the regions of Kédougou and Tambacounda in Senegal, the largest recorded outbreak yet. CHIKV is typically maintained in a sylvatic cycle in Senegal but its evolution and factors contributing to re-emergence are so far unknown in West Africa, leaving a gap in understanding and responding to recurrent epidemics. We produced, in real-time, the first locally-generated and publicly available CHIKV whole genomes in West Africa, to characterize the genetic diversity of circulating strains, along with phylodynamic analysis to estimate time of emergence and population growth dynamics. A novel strain of the West African genotype, phylogenetically distinct from strains circulating in previous outbreaks, was identified. This suggests a likely new spillover from sylvatic cycles in rural Senegal and potential of seeding larger epidemics in urban settings in Senegal and elsewhere.

Influence of HIV infection on cognition and overall intelligence in HIV-infected individuals: advances and perspectives.

It is now well understood that HIV-positive individuals, even those under effective ART, tend to develop a spectrum of cognitive, motor, and/or mood conditions which are contemporarily referred to as HIV-associated neurocognitive disorder (HAND), and which is directly related to HIV-1 infection and HIV-1 replication in the central nervous system (CNS). As HAND is known to induce difficulties associated with attention, concentration, and memory, it is thus legitimate and pertinent to speculate upon the possibility that HIV infection may well influence human cognition and intelligence. We therefore propose herein to review the concept of intelligence, the concept of cells of intelligence, the influence of HIV on these particular cells, and the evidence pointing to differences in observed intelligence quotient (IQ) scores between HIV-positive and HIV-negative individuals. Additionally, cumulative research evidence continues to draw attention to the influence of the gut on human intelligence. Up to now, although it is known that HIV infection profoundly alters both the composition and diversity of the gut microbiota and the structural integrity of the gut, the influence of the gut on intelligence in the context of HIV infection remains poorly described. As such, we also provide herein a review of the different ways in which HIV may influence human intelligence via the gut-brain axis. Finally, we provide a discourse on perspectives related to HIV and human intelligence which may assist in generating more robust evidence with respect to this issue in future studies. Our aim is to provide insightful knowledge for the identification of novel areas of investigation, in order to reveal and explain some of the enigmas related to HIV infection.

Analytical performances of the Xpert MTB/RIF assay using stool specimens to improve the diagnosis of pulmonary tuberculosis in Burkina Faso, a tuberculosis endemic country.

Timely diagnosis of Pulmonary Tuberculosis (PTB) is associated with good prognosis, but remains difficult in primary healthcare facilities and particularly in children and patients living with HIV. The aim of this study was to compare the GeneXpert ® MTB/RIF assay (Xpert) performed using a stool sample (3-5 g) and using the first Respiratory Tract Sample (RTS; i.e., sputum, bronchoalveolar or gastric aspirate; as normally done) concomitantly collected from 119 patients with suspected PTB to improve PTB diagnosis in Burkina Faso, a high tuberculosis burden country with limited resources. Overall, microbiological, microscopic and molecular analysis of the 119 first RTS and 119 stool specimens led to Mycobacterium tuberculosis complex detection in 28 patients (23 positive RTS cultures and 5 negative RTS cultures-RTS Xpert positive). When using the 28 clinical confirmed cases as reference standard, the sensitivities of the stool-based and RTS-based Xpert assays were not different (24/28, 85.7%, versus 26/28, 92.86%; p > 0.30), and 22 results were fully concordant. Considering the first RTS culture as the gold standard, the sensitivities of the stool-based and RTS-based Xpert assays to detect PTB in patients with positive RTS culture were 100% (23/23) and 91.3% (21/23), respectively (p >0.05). The stool-based Xpert assay specificity for excluding PTB was 99% (95/96) (compared with 95%, 91/96, when using RTS) and its negative and positive predictive values were 100% (95/95) and 96% (23/24), respectively. Compared with the 23 positive RTS cultures, the incremental yield rates of the RTS-based and stool-based Xpert assays were 4.2% (5/119) and 0.84% (1/119), respectively. Overall, our findings support using the stool-based Xpert assay as an alternative method for earlier PTB diagnosis, when RTS are difficult to obtain.

Corrigendum: Formulation of phage cocktails and evaluation of their interaction with antibiotics in inhibiting carbapenemase-producing Klebsiella pneumoniae in vitro in Kenya.

[This corrects the article DOI: 10.4102/ajlm.v11i1.1803.].

Seroprevalence of SARS-CoV-2 IgG and associated factors among people living with HIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso, a sub-Saharan African country.

OBJECTIVE: This study aimed to evaluate the seroprevalence of anti-SARS-CoV-2 IgG and factors associated with the infection among PLWHIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso. DESIGN: A retrospective cross-sectional study of plasma samples collected from March 9, 2020, and March 8, 2021, at the outpatient HIV referral center, before the introduction of the SARS-CoV-2 vaccine in Burkina Faso. METHODS: Anti-SARS-CoV-2 IgG were detected in plasma using DS-ЕIA-ANTI-SARS-CoV-2-G (S) kit. Logistic regressions were used to compare SARS-CoV-2 specific immune responses between groups and within subgroups. RESULTS AND DISCUSSION: A total of 419 plasma were subjected to serological diagnosis. None of the participants was vaccinated against COVID-19 during the period of sample collection, and 130 samples were positive for anti-SARS-CoV-2 IgG, giving a prevalence of 31.0% (95% CI 26.6-35.7). The median CD4 cell count was 661 cells/µL (IQR,422-928). Retailers had half the risk of being infected compared to housemaids with an OR of 0.49 (p = 0.028, 95% CI 0.26-0.91). Likewise, the risk of infection was 1.69 times higher in patients on integrase inhibitors compared to that of patients on non-nucleoside reverse transcriptase inhibitors (p = 0.020, 95% CI 1.09-2.63). CONCLUSION: Our study reveals a high seroprevalence among PLWHIV to SARS-CoV-2 during the first year of the pandemic. In addition, PLWHIV on integrase inhibitors are 1.69 times more likely to be infected than PLWHIV on non-nucleoside inhibitors, and this observation remains an intriguing topic that still needs to be clarified.

Long-term evolution of immunological and virological parameters in patients undergoing treatments for HIV-1 infection at the Day Hospital of Bobo-Dioulasso, Burkina Faso.

Introduction: antiretroviral therapy enables the suppression of the plasma viral load and the restoration of immune responses. Therapeutic failures are still observed in patients living with HIV despite the considerable benefits of antiretroviral therapy. This study aimed to describe the long-term evolution of immunological and virological parameters in patients undergoing treatments for HIV-1 at the Day Hospital of Bobo-Dioulasso in Burkina Faso. Methods: a retrospective descriptive and analytical study covering 10 years from 2009 was conducted at the Sourô Sanou University Hospital Center (CHUSS) in Bobo-Dioulasso. HIV-1-positive patients with at least two viral load measurements and two CD4 T cell counts were included in this study. Excel 2019 and RStudio were used to analyze the data. Results: a total of 265 patients were included in this study. The mean age of the patients was 48 ± 8.98 years and women accounted for 77.7% of the study population. A considerable decrease in the number of patients with TCD4 lymphocytes below 200 cells/µl from year 2 of treatment and a progressive increase in those with TCD4 lymphocytes above 500 cells/µl were observed in the study. Regarding the evolution of viral load, an increase in the proportions of patients with an undetectable viral load and a decrease in those with a viral load greater than 1000 copies/ml were noticed in years 2, 5, 6, and 8 of the follow-up. However, a decrease in the proportions of patients with undetectable viral load and an increase in those with viral load above 1000 copies/ml were observed in the years 4, 7, and 10 of follow-up. Conclusion: this study highlighted the different trends of viral load and LTCD4 evolution over 10 years of antiretroviral treatment. It showed a good immunovirological response was shown at the beginning of antiretroviral therapy, and then, a poor evolution of these markers at certain periods during the follow-up of HIV-positive patients.

Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance.

Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics.

Evaluation of the impact of COVID-19 in people coinfected with HIV and/or tuberculosis in low-income countries: study protocol for mixed methods research in Burkina Faso.

BACKGROUND: An issue of particular concern is the impact of the 2019 novel coronavirus (2019 nCOV) on the people coinfected with the Human Immuno-deficiency Virus (HIV) and/or tuberculosis (TB). Unfortunately, this interaction has not been well explored in African despite the large proportion of these risk populations living with HIV and/or patients and/or tuberculosis (TB) in the African region. This study aims to design a research protocol for assessment of the impact of coronavirus disease 2019 (COVID-19) on these risk populations in response to COVID-19 strategic plans in Burkina Faso by generating serological, epidemiological, virological, clinical and socio-anthropological evidence-based data. METHODS: A multidisciplinary research will be conducted in the city of Bobo-Dioulasso, Burkina Faso using mixed methods. Data will be collected from a cohort of people living with HIV and/or TB patients in the city (i) to determine the proportion of people with specific antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using retrospective data ; (ii) to determine the proportion of people infected with Covid-19 and the dynamics of viral loads and antibodies in these people based on prospective data; (iii) to identify circulating SARS-COV-2 variants and novel biomarkers using prospective data ; (iv) to analyze perceptions, community experiences and response strategies during the public health emergencies imposed by COVID-19 through a qualitative study. DISCUSSION: This study will generate factual and comprehensive data that will contribute in improving response strategies to COVID-19 and the other possible emerging diseases with keen interest on the risk populations living with HIV and/or TB infected patients.

Prevalence and Phenotypic and Molecular Characterization of Carbapenemase-Producing Gram-Negative Bacteria in Gabon.

Data collection and monitoring of carbapenemase-producing (CP) Gram-negative bacteria (GNB) are often limited. This study determined CP-GNB prevalence in Gabon and the genetic origins of the resistance genes. From January 2016 to March 2018, 869 clinically significant GNB isolates from inpatients and outpatients, and 19 fecal samples (inpatients) were analyzed in the main hospitals of Gabon. Fecal samples were screened using ChromID® CARBA SMART selective chromogenic medium biplates. Species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antibiotic susceptibility was tested using the disk diffusion method on Müller-Hinton agar, and resistance genes were assessed by multiplex polymerase chain reaction and sequencing. Overall, 1.61% of clinical isolates (14 of 869) and 5.26% of fecal samples (1 of 19) were CP-GNB. The CP-GNB rate was higher among inpatients (2.98%) than outpatients (0.33%), in intensive care units (28.57%, 4 of 14), and in urine samples (35.71%, 5 of 14). The most common CP-GNB were Klebsiella pneumoniae (53.33%) and Acinetobacter baumannii (26.67%). blaOXA-48 was the predominant carbapenemase-encoding gene (40%), followed by blaNDM-5 (33.33%). The A. baumannii multilocus sequence types ST2 and ST78, Enterobacter cloacae ST78, Escherichia coli ST2, and K. pneumonia ST48 and ST147 were found. These data indicate that CP bacteria are present in clinical and carriage samples. Preventive measures are needed to avoid the spread of resistance genes.

Characterization of extended-spectrum beta-lactamase and carbapenemase genes in bacteria from environment in Burkina Faso.

INTRODUCTION: This study aimed to characterize extended-spectrum beta-lactamase (ESBL) and carbapenemase genes in bacteria from the environment in Bobo-Dioulasso, Burkina Faso. METHODOLOGY: This study was conducted from January 18 to December 31, 2019. Environmental samples were collected from the effluents of Souro Sanou University Hospital Center and the wastewater treatment plant at Bobo-Dioulasso. MacConkey agar media supplemented with 4 µg/mL cefotaxime was used for bacterial growth, and identification of bacteria was performed using API 20E system (BioMerieux SA, Lyon, France). Antibiotic susceptibility testing, synergy test, carbapenem inactivation method and molecular characterization were performed. RESULTS: A total of 180 bacterial isolates were identified from the different sites with a predominance of Klebsiella oxytoca and Klebsiella pneumoniae (27.5%). All 180 bacterial isolates were ESBL producers and 18 (10.0%) of them produced carbapenemases. Out of the 180 bacterial isolates, DNAs of 98.9% (178/180) bacterial isolates were extracted and tested through polymerase chain reaction (PCR) for characterization of resistant genes. The study showed that 89.8% (160/178) carried the bla-CTX-M genes including 54.4 (87/160) from hospital effluents and 45.6 (73/160) from the wastewater treatment plant. Regarding the carriage of carbapenemase genes, 7.9 (14/178) blaNDM-1 was found in all the sites including 71.4% (10/14) from hospital effluents and 28.6 (4/14) from the wastewater treatment plant. blaOXA-48-like was only found in bacteria from hospital effluents and represented 2.2% (4/178). CONCLUSIONS: This study highlights the need to build hospital effluent treatment plants to reduce the load of resistant bacteria before discharging the effluents into the urban wastewater system.

Genomic Epidemiology of SARS-CoV-2 in Western Burkina Faso, West Africa.

BACKGROUND: After its initial detection in Wuhan, China, in December 2019, SARS-CoV-2 has spread rapidly, causing successive epidemic waves worldwide. This study aims to provide a genomic epidemiology of SARS-CoV-2 in Burkina Faso. METHODS: Three hundred and seventy-seven SARS-CoV-2 genomes obtained from PCR-positive nasopharyngeal samples (PCR cycle threshold score < 35) collected between 5 May 2020, and 31 January 2022 were analyzed. Genomic sequences were assigned to phylogenetic clades using NextClade and to Pango lineages using pangolin. Phylogenetic and phylogeographic analyses were performed to determine the geographical sources and time of virus introduction in Burkina Faso. RESULTS: The analyzed SARS-CoV-2 genomes can be assigned to 10 phylogenetic clades and 27 Pango lineages already described worldwide. Our analyses revealed the important role of cross-border human mobility in the successive SARS-CoV-2 introductions in Burkina Faso from neighboring countries. CONCLUSIONS: This study provides additional insights into the genomic epidemiology of SARS-CoV-2 in West Africa. It highlights the importance of land travel in the spread of the virus and the need to rapidly implement preventive policies. Regional cross-border collaborations and the adherence of the general population to government policies are key to prevent new epidemic waves.

Impact of mentoring on the implementation of the quality management system in clinical laboratories in Burkina Faso, West Africa.

In Burkina Faso, the implementation of the quality management system remains weak in diagnostic laboratories. Integrating mentoring into the life of clinical diagnostic laboratories, a qualified mentor is essential for quality system control. The objective of this study was to evaluate the impact of the mentoring process on quality improvement. Mentoring process was implemented at nine laboratories. The process consisted of a one-week mentor stay in the laboratory as one visit, with four in total. The SLIPTA checklist was used as a measurement tool. Two audits were performed (before and after the implementation of the mentoring process. The audit data were analyzed to estimate the effect of mentoring on quality improvement. A score difference of 24.55% was found significant between the two audits (paired Student's t-test p-value = 0.0002). The variables non-conformities, corrective/preventive actions, and facilities/safety have factored more than eight points between the two audits. However, the management/customer service and information one have only slightly increased (2.27 and 0.63, respectively). Mentoring has improved the quality management system in laboratories. However, some points of the process need to be improved to bring these laboratories toward international accreditation.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Formulation of phage cocktails and evaluation of their interaction with antibiotics in inhibiting carbapenemase-producing Klebsiella pneumoniae in vitro in Kenya.

Background: The development of alternative control measures, such as phage therapy or adjunctive therapy, is urgently needed to manage the dissemination of carbapenemase-producing Klebsiella pneumoniae. Objective: This study aimed to evaluate the therapeutic potential of formulated phage cocktails and their interaction with select antibiotics in inhibiting the growth of carbapenemase-producing K. pneumoniae clinical isolate in vitro in Kenya. Methods: The study was conducted from February 2021 to October 2021 at the Institute of Primate Research, Nairobi, Kenya. Phage cocktails were formulated based on the morphology and biological properties of precipitated Klebsiella phages. The efficacy of individual bacteriophages and phage cocktails as well as their combination with antibiotics were determined for their inhibitory activity on carbapenemase-producing K. pneumoniae (KP20). Results: The precipitated bacteriophages were members of Myoviridae, Siphoviridae and Podoviridae. Regarding the evaluation of the phage cocktails, the absorbances at 600 nm of the bacterial culture treated with the two-phage cocktail (2φ MA) ranged from 0.173 to 0.246 at 16 h and 20 h whereas it peaked from 2.116 to 2.190 for the positive control. Moreover, the results of the adjunctive therapy showed that the optical density at 600 nm of the bacterial culture treated with 2φ MA was 0.186 at 24 h post-incubation time while it was 0.099 with the bacterial culture treated with imipenem in combination with 2φ MA. Conclusion: This study demonstrated that the two-phage cocktail in combination with imipenem was able to synergistically delay the increase in carbapenemase-producing K. pneumoniae growth in vitro.

Antibody escape and global spread of SARS-CoV-2 lineage A.27.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

Assessment of Recovery Time, Worsening, and Death among Inpatients and Outpatients with COVID-19, Treated with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso.

OBJECTIVES: Our study aimed to assess the statistical relationship between the use of chloroquine phosphate or hydroxychloroquine plus azithromycin (CQ/HCQ + AZ) and virological recovery, disease worsening, and death among out- and inpatients with COVID-19 in Burkina Faso. METHODS AND DESIGNS: This was a retrospective observational study that compared outcomes in terms of time to recovery, worsening, and death in patients who received CQ/HCQ + AZ and those who did not using a multivariable Cox or Poisson model before and after propensity matching. RESULTS: Of the 863 patients included in the study, about 50% (432/863) were home-based follow-up patients and 50% were inpatients. Of these, 83.3% (746/863) received at least 1 dose of CQ/HCQ + AZ and 13.7% (118/863) did not. There were no significant differences in associated time to recovery for patients receiving any CQ/HCQ + AZ (adjusted HR 1.44; 95% CI 0.76-2.71). Similarly, there was no significant association between CQ/HCQ + AZ use and worsening (adjusted IRR 0.80; 95% CI 0.50-1.50). However, compared with the untreated group, the treated group had a lower risk of death (adjusted HR 0.20; 95% CI 0.10-0.44). CONCLUSIONS: The study provided valuable additional information on the use of CQ/HCQ in patients with COVID-19 and did not show any harmful outcomes of CQ/HCQ + AZ treatment.