High drug-pathogen mismatch in the management of invasive carbapenem-resistant Enterobacteriaceae infections at a tertiary hospital in Nigeria.

Objectives: This study aims to provide lacking data on antibiotics and treatment strategies used in the management of carbapenem-resistant Enterobacteriaceae (CRE) infections in Nigeria. Methods: A cross-sectional study was carried out at the University College Hospital in Ibadan. CRE isolated from routine culture of specimens from hospitalized patients from December 2021 to September 2022 was identified. Treatment information and other data were collected from the patients' medical records. Results: The hospital laboratory isolated CRE from 55 patients during the study period and 27 (49.1%) of them had data available for the study. The most frequently isolated CRE was Klebsiella spp. (13 of 27, 48.1%). Of the 24 patients who received empiric antibiotics, only two (8.3%) of their CRE isolates were susceptible. After receiving culture results, 18 (66.7%) patients were treated with at least one antibiotic, to which resistance was documented. Only three (11.1%) patients overall commenced or remained on an antibiotic, to which their CRE isolate was susceptible. Conclusions: Despite culture data, we found a high prevalence of drug-pathogen mismatch in CRE treatment, including new or persistent use of antibiotics, to which resistance was documented. Antimicrobial stewardship efforts need to be strengthened to specifically address CRE treatment and effective antibiotics need to be made accessible.

Clinical symptoms and faecal shedding of SARS-CoV-2 RNA among hospitalized COVID-19 patients: Implication for transmission.

SARS-CoV-2 shedding in human stool has been suggested as a probable route for faeco-oral transmission of the virus due to the availing evidence on the infectivity and pathogenicity of similar highly infectious respiratory viruses. Determining association of SARS-CoV-2 shedding in stools and presenting clinical status might be useful for prediction of the viral transmission spectrum and disease outcome. This study involved a descriptive cross-sectional survey of 91 consenting hospitalized, confirmed COVID-19 patients in Infectious Disease Isolation Centre, Oyo State, Nigeria. Socio-demographic characteristics and other ancillary data were collected from patient's hospital records with the aid of a structured investigator administered questionnaire. The laboratory detection of SARS-CoV-2 RNA in the stool of patients was performed using RT-PCR method. 27 (29.7%) of the 91 COVID-19 patients shed SARS-CoV-2 in their stools. The frequency of male (38.3%) patients shedding the virus in stools was higher than female (12.9%) patients (P = 0.012). Higher proportion of patients who had symptoms (41.2%) at admission shed the virus in their stool (P <0.007); particularly, fever (0.001), fatigue (0.003), headache (0.003), catarrh (0.001), and loss of smell (0.009). The frequency of viral shedding in stool was higher among patients with loss of taste (p = 0.028). Viral shedding in stool was significantly associated with low CT values (47.2%) and moderate CT value (21.4%) (P<0.05). Multivariate analysis showed that patients with moderate CT-value (OR = 0.28, 95% CI: 0.08-0.94, P = 0.039) and high CT-value (OR = 0.08, 95% CI: 0.01-0.80, P = 0.033) were less likely to shed the virus in stool. The gastrointestinal tract could be a route of SARS-CoV-2 transmission irrespective of the patients' clinical status. The low and moderate CT values of the nasopharyngeal swab is associated with shedding of the virus in patients' stools, although infectivity will depend on viral activity obtainable from further laboratory test analyses, such as viral culture.

Prevalence of rectal carbapenem resistant Enterobacterales carriage among patients attending healthcare facilities in Ibadan, Nigeria: a descriptive study.

BACKGROUND: Carbapenem Resistant Enterobacterales (CRE) infections are increasingly associated with or directly responsible for morbidity and mortality from bacterial infections in sub-Saharan Africa where there are limited antibiotic options. CRE rectal colonization of patients in healthcare facilities provides a reservoir of these organisms and could potentially cause invasive infections in these settings. The prevalence of rectal carriage among patients attending healthcare facilities in Nigeria has not been previously described. We set out to assess the prevalence of rectal CRE carriage and their antibiotic susceptibility patterns among patients attending healthcare facilities in Nigeria. METHODS: A descriptive cross-sectional study was carried out from December 2021 to September 2022 in Ibadan, in which patients attending primary, secondary and tertiary healthcare facilities were screened for rectal carriage of CRE by microscopy, culture and sensitivity of rectal swab specimens. RESULTS: A total of 291 patients were screened; 45 (15.5%), 66 (22.7%) and 180 (61.8%) at primary, secondary and tertiary healthcare facilities, respectively. All but one of them had received a third-generation cephalosporin or carbapenem in the preceding 30 days. The mean age was 28.8 years and 55.7% were male. Overall, 51 (17.5%) participants had CRE colonization, with 5(11.1%), 9(13.6%) and 37(20.6%) at primary, secondary and tertiary healthcare facilities, respectively (p = 0.243). Regarding antimicrobial susceptibility, 43(84.3%) CRE isolates were resistant to at least 3 different classes of antibiotics while two Escherichia coli isolates were resistant to all 5 classes of antibiotics tested. The lowest rates of CRE resistance were to tigecycline (6, 11.5%) and colistin (8, 15.7%). CONCLUSIONS: In this first study on CRE colonization in Nigeria, we found that a substantial proportion of patients in three levels of healthcare facilities had rectal carriage of CRE, including pan-resistant isolates. Active surveillance and appropriate infection prevention and control practices (IPC) need to be urgently strengthened to mitigate the risk of active CRE infection. TRIAL REGISTRATION: Not applicable.

Characteristics and outcomes of patients hospitalized with COVID-19 at a tertiary hospital in Nigeria.

Background: Data regarding the features and outcomes of hospitalized COVID-19 patients in Africa are increasingly available. Objectives: To describe socio-demographic, clinical and laboratory characteristics and outcomes of COVID-19 patients. Methods: A cross-sectional study of 86 adult patients hospitalized with COVID-19 between March and November 2020. Characteristics were described in survivors and non-survivors. Results: Mean age was 60.9±16.1 years, 53(61.6%) were male. Co-morbidities were found in 77(89.5%) patients. On severity, 6(7%) were mild, 23(26.7%) moderate, 51(59.3%) severe and 6(7%) critical. Oxygen saturation and respiratory rate were 71±22% and 38±11/minute in non-survivors and 90±7% and 31±7/minute in survivors respectively (p<0.001, p<0.001)). Overall mortality was 47.7% with no death among patients with mild disease and deaths in all patients with critical disease. Duration of hospitalization was 2.0(1.0-4.5) days in those who died and 12(7.0-15.0) days in those who survived (p<0.001). Of the 42 patients that received dexamethasone, 11(26.2%) died, while 31(73.8%) survived (p=<0.001). Conclusion: Most of the patients had co-morbidities and there was high mortality in patients with severe and critical COVID-19. Mean oxygen saturation was low and respiratory rate high overall. Factors associated with mortality included: Significantly greater hypoxia and tachypnea, less dexamethasone use and shorter hospitalization.

A multi-country phase 2 study to evaluate the suitcase lab for rapid detection of SARS-CoV-2 in seven Sub-Saharan African countries: Lessons from the field.

BACKGROUND: The COVID-19 pandemic led to severe health systems collapse, as well as logistics and supply delivery shortages across sectors. Delivery of PCR related healthcare supplies continue to be hindered. There is the need for a rapid and accessible SARS-CoV-2 molecular detection method in low resource settings. OBJECTIVES: To validate a novel isothermal amplification method for rapid detection of SARS-CoV-2 across seven sub-Sharan African countries. STUDY DESIGN: In this multi-country phase 2 diagnostic study, 3,231 clinical samples in seven African sites were tested with two reverse transcription Recombinase-Aided Amplification (RT-RAA) assays (based on SARS-CoV-2 Nucleocapsid (N) gene and RNA-dependent RNA polymerase (RdRP) gene). The test was performed in a mobile suitcase laboratory within 15 min. All results were compared to a real-time RT-PCR assay. Extraction kits based on silica gel or magnetic beads were applied. RESULTS: Four sites demonstrated good to excellent agreement, while three sites showed fair to moderate results. The RdRP gene assay exhibited an overall PPV of 0.92 and a NPV of 0.88. The N gene assay exhibited an overall PPV of 0.93 and a NPV 0.88. The sensitivity of both RT-RAA assays varied depending on the sample Ct values. When comparing sensitivity between sites, values differed considerably. For high viral load samples, the RT-RAA assay sensitivity ranges were between 60.5 and 100% (RdRP assay) and 25 and 98.6 (N assay). CONCLUSION: Overall, the RdRP based RT-RAA test showed the best assay accuracy. This study highlights the challenges of implementing rapid molecular assays in field conditions. Factors that are important for successful deployment across countries include the implementation of standardized operation procedures, in-person continuous training for staff, and enhanced quality control measures.

Seroprevalence of anti-SARS-CoV-2 specific antibodies in vaccinated and vaccine naïve adult Nigerians.

BACKGROUND: Reports on the evaluation of immune responses to different COVID-19 vaccines are limited. Similarly, effects of age and gender have not been well explored as variables that could impact on the vaccine-induced antibody response. Therefore, seroprevalence of anti-SARS-CoV-2 specific antibodies in vaccinated and vaccine naïve adult Nigerians was determined in this study. METHODOLOGY: A total of 141 adults were enrolled into this study. Presence or absence of SARS-CoV-2 infection was confirmed by real-time reverse-transcriptase polymerase-chain reaction (RT-PCR) assay on nasopharyngeal and oropharyngeal swab specimens. Anti-SARS-CoV-2 Specific IgG and IgM antibodies were qualitatively detected using a Rapid Diagnostic Test kit. RESULTS: Pre-vaccination, 77% of the study participants had never had PCR-confirmed COVID-19 test yet 66.7% of them were seropositive for SARS-CoV-2 antibodies. Of 111 COVID-19 vaccinated participants, 69.2% and 73.8% of them had SARS-CoV-2 specific IgG post-first and second doses of COVID-19 vaccine respectively. However, 23.1% and 21.4% of the participants who have had first and second doses respectively had no detectable anti-SARS-CoV-2 antibodies. The proportion of participants with SARS-CoV-2 specific IgG was insignificantly higher in those between the ages of 18-40 years and 41-59 years compared with individuals aged ≥60 years. No significant association was observed between gender and seropositivity for SARS-CoV-2 antibodies. CONCLUSION: There is high SARS-CoV-2 antibody seroprevalence among Nigerian adults who never had PCR-confirmed COVID-19. Also, there is the need for anti-SARS-CoV-2 antibodies screening post vaccination as this could be essential in achieving herd immunity. Age and gender do not seem to have significant association with seropositivity.

A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19.

Background: The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19. Methods: This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286). Results: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2-28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341-2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251-1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797-2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion: Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].

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.

Prevalence of hepatitis B virus core antibodies among blood donors in Nigeria: Implications for blood safety.

Background: Anti-hepatitis B core antibody (anti-HBc) testing improves transfusion safety by detecting past and current hepatitis B virus (HBV) infection while detecting hepatitis B surface antigen (HBsAg) in serology-negative HBV infection. However, occult HBV infection (OBI) (serum or liver HBV DNA-positive but HBsAg-negative) remains unaddressed among replacement blood donors - family members or friends who donate to replace blood transfused to a relative. Objective: This study assessed risk factors for a positive anti-HBc test among donors with OBI and determined the anti-HBc-positive status of replacement donors. Methods: The study was conducted at the University College Hospital Blood Bank, Ibadan, Nigeria, using blood samples collected from blood donors between April 2019 and May 2019. Donors were screened for HBsAg by rapid diagnostic test (RDT) and enzyme-linked immunosorbent assay (ELISA) and anti-HBc by ELISA, while HBV DNA was detected using a semi-nested polymerase chain reaction. Results: Of the 274 participants, 15 (5.5%) were HBsAg-positive by RDT and 36 (13.1%) by ELISA, while 133 (48.5%) were anti-HBc positive. Out of 232 HBsAg-negative donors, 107 (46.1%) were anti-HBc positive. Of the 107 HBsAg-negative but anti-HBc-positive samples, only one (0.93%) was HBV DNA-positive. The HBV DNA-positive donor was HBsAg-negative by both RDT and ELISA tests. Conclusion: This study establishes a potential risk for HBV transmission from isolated anti-HBc-positive donors to blood recipients. HBc immunoglobulin (antibody) M testing to identify blood units requiring further screening with polymerase chain reaction to detect OBI can prevent HBV transmission through blood transfusion.

The African Female Breast Cancer Epidemiology Study Protocol.

Breast cancer is now the commonest cancer in most sub-Saharan African countries. Few studies of the epidemiology and genomics of breast cancer and its molecular subtypes in these countries have been done. The African Female Breast Cancer Epidemiology (AFBRECANE) study, a part of the Human Heredity and Health in Africa (H3Africa) initiative, is designed to study the genomics and epidemiology of breast cancer and its molecular subtypes in Nigerian women. We link recruitment of breast cancer cases at study sites with population-based cancer registries activities to enable ascertainment of the incidence of breast cancer and its molecular subtypes. We use centralized laboratory processing to characterize the histopathological and molecular diagnosis of breast cancer and its subtypes using multiple technologies. By combining genome-wide association study (GWAS) data from this study with that generated from 12,000 women participating in our prospective cohort study of cervical cancer, we conduct GWAS of breast cancer in an entirely indigenous African population. We test associations between dietary intakes and breast cancer and focus on vitamin D which we measure using dietary intakes, serum vitamin D, and Mendelian randomization. This paper describes the AFBRECANE project, its design, objectives and anticipated contributions to knowledge and understanding of breast cancer.

Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria.

Disparities in SARS-CoV-2 genomic surveillance have limited our understanding of the viral population dynamics and may delay identification of globally important variants. Despite being the most populated country in Africa, Nigeria has remained critically under sampled. Here, we report sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. In early 2021, most isolates belonged to the Alpha "variant of concern" (VOC) or the Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after expansion of an otherwise rare Delta sub-lineage. Spike protein from the Eta variant conferred increased infectivity and decreased neutralization by convalescent sera in vitro. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally and represented a VOC in early 2021. These results demonstrate a distinct distribution of SARS-CoV-2 lineages in Nigeria, and emphasize the need for improved genomic surveillance worldwide.

Qualitative exploration of health system response to COVID-19 pandemic applying the WHO health systems framework: Case study of a Nigerian state.

Pandemics can result in significantly high rates of morbidity and mortality with higher impact in Lower- and Middle-Income Countries like Nigeria. Health systems have an important role in a multi-sector response to pandemics, as there are already concerns that COVID-19 will significantly divert limited health care resources. This study appraised the readiness and resilience of the Nigerian health system to the COVID-19 pandemic, using Oyo State, southwest Nigeria, as a case study. This study was a cross-sectional qualitative study involving key informant and in-depth interviews. Purposive sampling was used in recruiting participants who were members of the Task Force on COVID-19 in the state and Emergency Operations Centre (EOC) members (physicians, nurses, laboratory scientists, "contact tracers", logistic managers) and other partners. The state's health system response to COVID 19 was assessed using the WHO health systems framework. Audio recordings of the interviews done in English were transcribed and thematic analysis of these transcripts was carried out using NVIVO software. Results show that the state government responded promptly by putting in place measures to address the COVID-19 pandemic. However, the response was not adequate owing to the fact that the health system has already been weakened by various challenges like poor funding of the health system, shortage of human resources and inadequate infrastructure. These contributed to the health system's sub-optimal response to the pandemic. In order to arm the health system for adequate and appropriate response during major health disasters like pandemics, fundamental pillars of the health system-finance, human resources, information and technology, medical equipment and leadership - need to be addressed in order to have a resilient health system.

Frequency of Hepatitis B Virus Envelope Antigen and Antibodies Among Chronic Carriers in Ibadan, Nigeria.

Hepatitis B virus (HBV) infection is a major health challenge in sub-Saharan Africa with a prevalence rate of >7%. It is an important clinical problem due to its potential adverse sequelae, including hepatocellular carcinoma. The additional challenge of its associated chronic infection makes its prevention difficult despite the widely available vaccine. Infectious chronic HBV carriers are likely to be the most common source of HBV infection in the community. This study aims to study the degree of infectiousness of HBV carriers by testing for HBV envelope antigen (HBeAg) and antibody among HBV carriers attending the gastrointestinal clinic at University College Hospital (UCH, Ibadan, Nigeria). This is a cross-sectional study among 129 consecutively recruited HBV infected individuals who gave informed consent to participate in the study. The participants of the study were recruited from clients attending the gastrointestinal clinic of UCH. The sera obtained from the participants were tested for HBsAg, HBeAg, and antibodies to HBV envelope antibodies (HBeAb) using commercially available enzyme-linked immunosorbent assay (ELISA) test kits by DIA.PRO (Diagnostic Bioprobes Srl, Milan, Italy) according to the manufacturer's instruction. Of 129 samples collected, 63 (48.8%) tested positive for HBeAg, whereas 72 (55.8%) tested positive for HBeAb (p = 0.012); HBeAg prevalence was higher in females than males and also prevalent among the age group of 31-40 years. Seventy-four (57.4%) of the participants also tested positive for both HBeAg and HBeAb, whereas 55 (42.6%) were negative for both. This study shows that there is a high level of infectiousness among HBsAg-positive individuals in Ibadan, Nigeria.

Coincident rapid expansion of two SARS-CoV-2 lineages with enhanced infectivity in Nigeria.

The emergence of new SARS-CoV-2 variants with enhanced transmissibility or decreased susceptibility to immune responses is a major threat to global efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Disparities in viral genomic surveillance capabilities and efforts have resulted in gaps in our understanding of the viral population dynamics across the globe. Nigeria, despite having the largest population of any nation in Africa, has had relatively little SARS-CoV-2 sequence data made publicly available. Here we report the whole-genome sequences of 74 SARS-CoV-2 isolates collected from individuals in Oyo State, Nigeria in January 2021. Most isolates belonged to either the B.1.1.7 Alpha "variant of concern" or the B.1.525 Eta lineage, which is currently considered a "variant of interest" containing multiple spike protein mutations previously associated with enhanced transmissibility and possible immune escape. Nigeria has the highest reported frequency of the B.1.525 lineage globally with phylogenetic characteristics consistent with a recent monophyletic origin and rapid expansion. Spike protein from the B.1.525 lineage displayed both increased infectivity and decreased neutralization by convalescent sera compared to Spike proteins from other clades. These results, along with indications that the virus is outpacing the B.1.1.7 lineage in Nigeria, suggest that the B.1.525 lineage represents another "variant of concern" and further underline the importance of genomic surveillance in undersampled regions across the globe.

Association of the ABO blood group with SARS-CoV-2 infection in a community with low infection rate.

BACKGROUND AND OBJECTIVES: Reports on the association of the ABO phenotypes with infection by the SARS-CoV-2 virus have mostly come from countries with high infection rates. This study examined the possible association between SARS-CoV-2 infection and the ABO phenotype in Black Africa. MATERIALS AND METHODS: This report is from a single centre where both asymptomatic and symptomatic patients were quarantined. At the time of this report, Oyo State, Nigeria had carried out 15 733 tests of which 3119 were positive for the virus with 1952 recoveries and 37 deaths. The ABO distribution of patients was compared with that of a blood donor population. RESULTS: Of the 302 participants, 297 (98%) had their blood group determined, asymptomatic and symptomatic individuals were 123 (40·7%) and 179 (59·3%) respectively. Blood group O was significantly less represented among the patients (P < 0·01) while blood groups B and AB were significantly more represented (P < 0·01, P = 0·03 respectively). Patients with anti-B (groups A and O) were significantly less represented than those without anti-B (B and/or AB): B and AB (P < 0·001), B (P = 0·002), AB (P = 0·01). There was no difference in the blood group distribution of symptomatic and asymptomatic patients (χ2 (3, N = 302) = 2·29; P = 0·51), but symptomatic patients with anti-A (groups B and O) were more represented than asymptomatic patients with anti-A (χ2 4·89; P = 0·03). CONCLUSION: The higher prevalence of blood group O and more potent beta haemolysins (anti-B antibodies) are likely reasons for the lower infectivity by the SARS-CoV-2 virus and severity of COVID-19 disease in the community.

Efficacy and safety of nitazoxanide plus atazanavir/ritonavir for the treatment of moderate to severe COVID-19 (NACOVID): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19. TRIAL DESIGN: This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial. PARTICIPANTS: Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward. INCLUSION CRITERIA: Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening. INTERVENTION AND COMPARATOR: Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria. MAIN OUTCOME MEASURES: Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs. RANDOMISATION: Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities. BLINDING: None, this is an open-label trial. NUMBER TO BE RANDOMISED (SAMPLE SIZE): 98 patients (49 per arm). TRIAL STATUS: Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534 . FULL PROTOCOL: The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Assessment of hepatitis B surface antigen negative blood units for HBV DNA among replacement blood donors in a hospital based blood bank in Nigeria.

BACKGROUND: Hepatitis B virus infection is one of the greatest threats to blood safety all over the world. The laboratory algorithm based on only the detection of hepatitis B surface antigen (HBsAg) leaves a gap for infected HBsAg negative donors to donate blood during the "window period" (WP) and late stages of infection. OBJECTIVE: To estimate the frequency of the presence of HBV deoxyribonucleic acid (DNA) in HBsAg negative blood units screened using two different assays for HBsAg in a high endemic region. METHODS: Frozen serum aliquot of 100 replacement blood donors who donated blood units that were HBsAg negative were retrieved and tested for HBV DNA. Sample positive for HBV DNA was sequenced by Sanger's method, genotyped and the viral load was determined. RESULTS: One sample (1%) was positive for HBV DNA. The HBV viral load of the sample was 768,000 IU/ml. The partial S-gene of the Hepatitis B virus isolated was genotype E using the NCBI viral genotyping tool. CONCLUSIONS: There is still a risk of HBV infected blood unit escaping detection when donor testing is limited to HBsAg screening. The use of NAT which can substantially reduce HBV infected blood donors from the donor pool should be considered.

Changes in Selected Renal Function Parameters of Newly Admitted COVID-19 Patients from One Infectious Diseases Center in Ibadan, Nigeria: Indication for Immunopathology.

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) enters the host cells through attachment to the Angiotensin Converting Enzyme-2 receptors (ACE-2) on the host cells. ACE-2 is known to affect renal functions, vasoconstriction and fluid homeostasis. Thus, the impact of SARS-CoV-2 infection on renal functional parameters is worth investigating. Plasma obtained from whole blood samples collected from newly diagnosed COVID-19 patients were analysed for albumin, urea, creatinine, Na, K, Cl and HCO3 using auto analysers. All newly diagnosed patients were immediately admitted for managed at the Infectious Disease Center, Olodo in Ibadan the capital of Oyo State, South Western Nigeria. The results obtained were evaluated to determine the frequency of derangements in the renal parameters of patients with the COVID-19 disease. It was observed that 57.1%, 37.8%, 32.7%, 28.1%, 18.7%, 17.8% and 3.4% of newly diagnosed COVID-19 patients had values of Cl, creatinine, albumin, Na, K, HCO3 and urea respectively outside the reference ranges. While 43.3%, 4.7%, 2.5%, 2.5%, 2.0%, 1.7% and 1.0% of COVID-19 patients had values of Cl, creatinine, Na, K, albumin, Urea and HCO3 respectively above the reference ranges. Of all admitted patients, 33.1%, 30.7%, 25.6%, 16.8%, 16.3%, 13.8% and 1.7% had creatinine, albumin, Na, HCO3, K, Cl and urea values respectively below reference ranges. The changes in renal function parameters of newly diagnosed COVID-19 patients portend that renal failure is imminent in poorly managed COVID-19 patients and this has immunopathology implications during SAR-COV-2 infection.