Preliminary Study on Open Labelled Randomized Controlled Trial of the Safety and Efficacy of Hydroxychloroquine and Chloroquine Phosphate for the Treatment of Persons Infected with 2019 Coronavirus Disease in Nigeria.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 is a leading cause of ill-health and deaths worldwide. Currently, COVID-19 has no known widely approved therapeutics. Thus, the need for effective treatment. OBJECTIVES: We investigated the safety and efficacy of two (2) therapeutic agents; chloroquine phosphate (CQ), 2- hydroxychloroquine (HCQ) and a control (standard supportive therapy) among hospitalized adults with COVID-19. METHODS: The clinical trial was done in accordance to the World Health Organization master protocol for investigational therapeutics for COVID-19. Atotal of 40 participants with laboratory-confirmed positive COVID-19 were enrolled. Blood samples and oropharyngeal (OP) swabs were obtained on days 1,3,15 and 29 for safety and efficacy assessments. RESULTS: The baseline demographics showed that the median ages in years (range) were 45 (31-57) in CQ, 45 (36.5-60.5) in HCQ, 43 (39.5-67.0) and 44.5 (25.3-51.3) in the control (P<0.042).At randomization, seven (7) participants were asymptomatic, thirty-three (33) had mild symptoms, eight (8) had moderate symptoms while three (3) had severe symptoms. The average day of conversion to negative COVID-19 was 15.5 days for CQ, 16 days for HCQ and 18 days for the control(P=0.036). CONCLUSION: The safety assessment revealed no adverse effect of the drugs in COVID-19 patients after treatment. These findings proved that chloroquine and hydroxychloroquine are effective for the treatment of COVID-19 among hospitalized adults. It also confirmed that they are safe.

CONTEXTE: Le coronavirus du syndrome respiratoire aigu sévère 2 (SARS-CoV-2),agentcausaldelaCOVID-19, est l'unedes principales causes demaladie et de décès dans le monde. À l'heure actuelle, il n'existe aucun traitement largement approuvé pour la COVID-19. Ainsi, ilya un besoin de traitement efficace. OBJECTIFS: Nous avons étudié l'innocuité et l'efficacité de deux (2) agents thérapeutiques, le phosphate de chloroquine (CQ) et l'hydroxychloroquine (HCQ), ainsi qu'un groupe témoin (traitement de soutien standard) chez des adultes hospitalisés atteints de la COVID-19.MÉTHODES: L'essai clinique a été mené conformément au protocole maître de l'Organisation mondiale de la santé pour les thérapeutiques à l'étude de la COVID-19. Au total, 40 participants atteints de la COVID-19, confirmée en laboratoire, ont été in scrits. Des échantillons de sang et des prélèvements oropharyngés (PO) ont été effectuésauxjours1,3,15et29pourévaluerl'innocuitéetl'efficacité. RÉSULTATS: Les données démographiques initiales ont révélé que l'âge médian en années (plage) était de 45 (31-57) pour le groupe CQ, de 45 (36,5-60,5) pour le groupe HCQ, de 43 (39,5-67,0) et de 44,5 (25,3-51,3) pour le groupe témoin (P<0,042). À la randomisation, sept (7) participants étaient asymptomatiques, trente-trois (33) présentaient des symptômes bénins, huit(8) avaient des symptômes modérés, tandis que trois(3) avaient des symptômes graves. Le jour moyende conversionentest COVID-19 négatif était de 15,5 jours pour le groupe CQ, de 16 jours pour le groupe HCQ et de 18 jours pourle groupe témoin (P=0,036). CONCLUSION: L'évaluation de la sécurité n'a révélé aucun effet indésirable des médicaments chez les patients atteints de la COVID-19 après le traitement. Ces conclusions ont prouvé que la chloroquine et l'hydroxychloroquine sont efficaces pour le traitement de la COVID-19 chez les adultes hospitalisés. Cela a également confirmé qu' ilssont sûrs. Mots-clés: COVID-19, SARS-CoV-2, essai clinique, innocuité, efficacité, thérapeutiques.

Determinants of Antimicrobial Use for Covid-19 Related Symptoms among Nigerians.

BACKGROUND: Antimicrobial use plays a key role in development and spread of antimicrobial resistance. Following the global coronavirus disease 2019 (COVID-19) pandemic and the report of the first confirmed case in Nigeria, several states embarked on either a full or partial lockdown as a measure to prevent or curtail the spread of the virus with its attendant challenges. This survey was designed to provide a snapshot of public antimicrobial use and common perception related to antimicrobial use for COVID-19 related symptoms among Nigerian populace. METHODS: We developed and tested a 29-question electronic questionnaire with Google forms asking respondents about their antimicrobial use and perceptions regarding appropriate antimicrobial use for real or perceived symptoms during the outbreak period. Respondents aged 18 years and above were recruited through crowd sourcing and they received the link to the survey tool through emails and social media including WhatsApp, Twitter, Facebook, LinkedIn, and Instagram. All data analysis was performed using SPSS version 26.0. RESULTS: A total of 410 responses were received from the six geopolitical zones in Nigeria comprising 200 (48.8%) females and 210 (51.2%) males. Majority (62.9%) of the respondents had taken antimicrobials in the 3 months period preceding the survey, while less than half (46.8%) received prescription for it. Previous intake of antimicrobial for similar illness was a predictor of antimicrobial intake (OR: 0.55, 95%CI: 0.30-1.01). The most consumed antimicrobial was antimalarial drugs, specifically Artemisinin-based combination therapy (43.4%), followed by antibiotics [Ciprofloxacin (20.2%)]. CONCLUSION: There was high levels of antimicrobial use for COVID-19 related symptoms by the Nigerian public. This is likely to escalate the already high prevalence of antimicrobial use previously reported and may further fuel the emergence of antimicrobial resistance.

CONTEXTE: L'utilisation d'antimicrobiens joue un rôle clé dans le développement et la propagation de la résistance aux antimicrobiens. À la suite de la pandémie mondiale de coronavirus 2019 (COVID-19) et du rapport du premier cas confirmé au Nigéria, plusieurs États se sont engagés dans un verrouillage complet ou partiel en tant que mesure pour prévenir ou freiner la propagation du virus avec ses défis associés. Cette enquête a été conçue pour fournir un aperçu de l'utilisation publique des antimicrobiens et de la perception commune liée à l'utilisation des antimicrobiens pour les symptômes liés au COVID-19 parmi la population nigériane. MÉTHODES: Nous avons développé et testé un questionnaire électronique de 29 questions avec des formulaires Google interrogeant les répondants sur leur utilisation d'antimicrobiens et leurs perceptions concernant l'utilisation appropriée d'antimicrobiens pour les symptômes réels ou perçus pendant la période d'épidémie. Les répondants âgés de 18 ans et plus ont été recrutés via le crowdsourcing et ils ont reçu le lien vers l'outil d'enquête via des e-mails et des médias sociaux, notamment WhatsApp, Twitter, Facebook, LinkedIn et Instagram. Toutes les analyses de données ont été effectuées à l'aide de la version 26.0 de SPSS. RÉSULTATS: Un total de 410 réponses ont été reçues des six zones géopolitiques du Nigéria comprenant 200 (48,8%) femmes et 210 (51,2%) hommes. La majorité (62,9%) des répondants avaient pris des antimicrobiens au cours des 3 mois précédant l'enquête, tandis que moins de la moitié (46,8%) en avaient reçu une prescription. La prise antérieure d'antimicrobiens pour une maladie similaire était un prédicteur de l'ingestion d'antimicrobiens (OR: 0,55, IC à 95%: 0,30-1,01). L'antimicrobien le plus consommé était les antipaludiques, en particulier les associations thérapeutiques à base d'artémisinine (43,4%), suivis des antibiotiques [Ciprofloxacine (20,2%)]. CONCLUSION: Il y avait des niveaux élevés d'utilisation d'antimicrobiens pour les symptômes liés au COVID-19 par le public nigérian. Cela est susceptible d'augmenter la prévalence déjà élevée de l'utilisation d'antimicrobiens rapportée précédemment et peut encore alimenter l'émergence de la résistance aux antimicrobiens.

Detection and molecular characterization of a first isolate of rabbit haemorrhagic disease virus in Nigeria.

Rabbit haemorrhagic disease virus (RHDV) was recovered from necropsied rabbits that died during an outbreak characterized by epistaxis, incoordination, paralysis, and multi-organ haemorrhages in Ilorin, Nigeria. The haemagglutination test (HA) and RT-PCR assay targeted against a fragment of the RHDV VP60 gene were performed on liver, spleen, and kidney homogenates; faeces; and urine obtained from the rabbits. Amplicons were purified, sequenced, and phylogenetically analysed. The liver homogenates yielded the highest HA titres while RT-PCR of liver, spleen, and kidneys yielded the expected 1252 bp band. Sequence and phylogenetic analyses revealed that the Nigerian RHDV strain (RHDV/NGR/ILN/001) was 98.57%, 97.95%, and 96.70% homologous with RHDV2 (RHDVGI.2) strains from the Netherlands, Germany, and France, respectively. RHDV/NGR/ILN/001 induced tracheal, intestinal, and mediastinal lymph node haemorrhages, pulmonary oedema and congestion, and enlarged, necrotic liver in experimentally inoculated rabbits. The implications of this study, which is the first report of RHDV in Nigeria, are discussed.

Prevalence and Clinical Characteristics of Coronavirus Disease 2019 Seen at a Testing Centre in Lagos Nigeria.

BACKGROUND: The SARS-CoV-2 infection continues to ravage the global community since it was declared a pandemic. The socio-demographic and clinical characteristics defining the disease are mainly from Europe and Asia. The disease symptomatology is similar to the prevalent diseases in our environment, this could result in the delay in prompt identification and appropriate management of suspected cases toward combating community transmission. This study evaluates the prevalence, socio-demographic and clinical characteristics of positive cases of COVID -19. METHODS: This was a retrospective cohort study. Data on the socio-demographic, clinical characteristics and the results of the SARS-CoV-2 test of participants at the Nigerian Institute of Medical Research [NIMR] Modified Drive-through Centre for COVID-19 test sample collection over two months [24th February 2020- 27th April 2020] were retrieved from the electronic medical records (EMR). Data obtained were analyzed using SPSS version 22.0. RESULTS: A total number of 481 clients were evaluated in this review. The prevalence of SARS-CoV-2 infection in the population was 14.6%. The mean age of the positive cases was 42.2 [±15.9] years. The common symptoms reported by the positive cases were fever (40.0%), cough (32.9%), sore throat (17.1%) and running nose (15.7%). Fever depicted statistical significance with positive cases with the majority being of mild to moderate clinical severity. CONCLUSION: The prevalence of SARS-CoV-2 infection among this cohort was 14.6% with a male preponderance. Fever and sore throat were the variables that predicted SARS CoV-2 infection among our cohort.

Serological and virological markers of nigerian patients with hepatitis B infection.

BACKGROUND: The natural history of chronic hepatitis B virus (HBV) infection and the spectrum of diseases attributable to chronic hepatitis B are diverse. It is estimated that 15%-25% of chronic carriers will die from complications of progressive disease such as liver cirrhosis, hepatocellular carcinoma, and hepatic decompensation. The main aim of this study is to evaluate the serological and virological profile of patients with hepatitis B infection to enhance the evaluation of the natural history of viral hepatitis in an endemic population. METHODS: Characteristics of hepatitis B surface antigen (HBsAg) patients (2010-2016) were extracted from the database of a reference laboratory in Lagos. These included serological tests for hepatitis B antigens (HBeAg, HBsAg), antibodies (anti-HBcIgM, anti-HBeAb) (DIA.PRO), and HBV DNA (Roche Diagnostics). SPSS version 20.0 was used for data analysis. RESULTS: Of the 1,983 patients, 1,252 were male and 731 female. HBeAg was detected in 8.0% (128/1,605) of the subjects, anti-HBe was positive in 90.0% (1,257/1,396), while HBcore subclass IgM antibody was detected in 12.6% (116/930). Detectable HBV DNA was identified in 1,781 (89%), with viral load exceeding 2,001 IU/mL in 712 (35.9%) subjects. HBV viral loads >200,000 IU/mL were more frequently detected in HBeAg-positive compared with HBeAg-negative subjects (65.7% vs 4.9%, P < 0.0001). CONCLUSION: We have demonstrated the predominance of low replicative phase HBV infection and highlighted the importance of HBeAg-negative infections that may require antiviral therapy. HBeAg-positive infections occurred significantly in younger adults with new or acute infections. Our findings have implications for patient evaluation and planning of hepatitis treatment programs.

Discordant rapid HIV tests: lessons from a low-resource community.

OBJECTIVES: HIV rapid antibody tests are widely used in Africa, but dual testing sometimes produces discordant results. It is not clear if discordant rapid HIV tests should always heighten suspicion by frontline health workers that early HIV infection is present. Some studies have reported that discordant rapid tests have value for identifying early HIV infection in high HIV prevalence populations. It is not known if rapid test performance influenced this conclusion, or if this observation will hold true for low HIV prevalence populations. We therefore explored the occurrence of discordant rapid HIV tests in a low-resource community. METHODS: A cross-sectional sample of HIV status-unaware adults with recent exposure to unsafe sex was assessed using a validated risk-based tool (University of North Carolina (UNC)-Malawi Risk Screening Score) for acute HIV infection. Participants received rapid testing with Determine™ HIV 1/2 and Uni-Gold™ HIV assays, plus plasma HIV-1 antigen testing with the COBAS® Ampliprep/COBAS® Taqman® HIV-1 assay, followed by western blot in those with detected HIV-1 antigen. RESULTS: Of 408 participants, 1.0% were confirmed to have established HIV infection. The discordance between rapid tests at initial screening was 2.45 and 2.94% when the two assays were used sequentially and simultaneously, respectively. Discordant rapid tests were strongly associated with risk scores > 2 [odds ratio (OR) 10.88; 95% confidence interval (CI) 2.35-50.43], and with detected HIV-1 RNA (OR 26.06; 95% CI 3.91-173.60). CONCLUSIONS: When the sample occurrence of discordance between the first and second tests is below 5%, discordant rapid tests in an adult with sexual risk behaviour should trigger strong suspicion of early HIV infection in low HIV prevalence populations.

Immunological and virological response to haart in HIV-1 patients co-infected with hepatitis B and C viruses.

BACKGROUND: Among the countries highly endemic for viral hepatitis, Nigeria is found. Information on how triple infected persons (HIV, HBV, and HCV) fare on HAART in the country is lacking. Laboratory based investigation was carried out to assess the virological and immunological parameters of HIV-1 infected patients co-infected with Hepatitis B and C, accessing care at the Nigerian Institute of Medical Research. It was a case controlled study. OBJECTIVES: The study aimed to compare the laboratory data of HIV-HBV-HCV patients seen between 2006 and 2009 with HIV-1 monoinfected patients in the same period, on HAART according to the national guideline and followed up for 12 months. METHODS: Detection of Hepatitis B surface Antigen (HBsAg) and Hepatitis C Virus Antibody (HCVAb) were assayed using ELISA techniques (Bio Rad and DIA PRO respectively). The CD4 and HIV viral load were determined using the Cyflow Counter/Kits (Partec) and the Amplicor HIV-1 Monitor Test V1.5 (Roche) techniques respectively. RESULTS: Forty-one (0.4%) of the 10,214 HIV-1 patients seen during the period were co-infected with both HBV and HCV. Over the 12 month-period, median HIV-1 viral load and CD4 count reduced and increased respectively (12,205-200 RNA copies/mL; 210-430 cells/mL from baseline - 12th month), and for the HIV-1 monoinfected patients (36,794-200 RNA copies/mL [p=0.5485] and 206-347 cells/mL [p=0.7703] from baseline - 12th month). CONCLUSION: There seems to be no significant influence of hepatitis B and C in HIV infection on HAART judging by the CD4 and viral load profiles which were similar in the two groups.

Genetic studies in the Nigerian population implicate an MSX1 mutation in complex oral facial clefting disorders.

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck, with a worldwide prevalence of 1 in 700 births. They are commonly divided into CL(P) and CP based on anatomic, genetic, and embryologic findings. A Nigerian craniofacial anomalies study (NigeriaCRAN) was set up in 2006 to investigate the role of gene-environment interaction in the origin of orofacial clefts in Nigeria. SUBJECTS AND METHODS: DNA isolated from saliva from Nigerian probands was used for genotype association studies and direct sequencing of cleft candidate genes: MSX1 , IRF6 , FOXE1, FGFR1 , FGFR2 , BMP4 , MAFB, ABCA4 , PAX7, and VAX1 , and the chromosome 8q region. RESULTS: A missense mutation A34G in MSX1 was observed in nine cases and four HapMap controls. No other apparent causative variations were identified. Deviation from Hardy Weinberg equilibrium (HWE) was observed in these cases (p = .00002). A significant difference was noted between the affected side for unilateral CL (p = .03) and bilateral clefts and between clefts on either side (p = .02). A significant gender difference was also observed for CP (p = .008). CONCLUSIONS: Replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the development of CL(P).

Establishment of reference values of CD4 and CD8 lymphocyte subsets in healthy Nigerian adults.

A total of 2,570 apparently healthy human immunodeficiency virus-negative adults from the six geopolitical zones in the country were enrolled in our study in 2006. The samples were assayed using the Cyflow technique. Data were analyzed using the Statistical Package for Social Scientists (SPSS). The majority (64%) of the participants had CD4 counts within the range of 501 to 1,000 cells/microl. The reference range for CD4 was 365 to 1,571 cells/microl, while the reference range for CD8 was 145 to 884 cells/microl.

Comparison of Dynabeads and Capcellia methods with FACScount for the estimation of CD4 T-lymphocyte levels in HIV/AIDS patients in Lagos, Nigeria.

OBJECTIVE: To compare the efficacy of the Capcellia assay and the Dynabeads technique against the FACScount technique in the estimation of CD4 T-lymphocytes within a Nigerian setting. DESIGN: Prospective study. SETTING: Urban area in Nigeria. SUBJECTS: Ninety seven subjects (51 HIV seronegative and 46 HIV seropositive adults) seen in the blood banks and two out patient clinics in Lagos within the study period. MAIN OUTCOME MEASURES: Dynadeads technique with a higher correlation coefficient is a feasible alternative to the FACScount method. RESULTS: There was an overall correlation coefficient of r = 0.75 for CD4 cell counts as determined by the Dynabeads technique in comparison with the FACScount method. Also, an overall correlation coefficient of r = 0.17 for CD4 cell counts as determined by the Capcellia technique against the FACScount method. CONCLUSION: Dynabeads technique is simple to carry out and cheaper in terms of demand for human expertise and infrastructural requirements than the FACScounts. Therefore, it was recommended for use in the laboratory for monitoring of ARV therapy in Nigeria and any other resource poor

Evaluation of the Nigerian national antiretroviral (ARV) treatment training programme.

There is an understanding that greater availability of HIV treatment for the 40.3 million people currently infected with HIV is a humanitarian imperative that could prolong the lives of millions, restore economic productivity, and stabilise societies in some of the world's hardest-hit regions. The Nigerian government recognises that the country has the third highest burden of infection, with people living with HIV estimated to total 4.0 million, and so in 2002 commenced the implementation of one of Africa's largest antiretroviral (ARV) treatment programmes. A successful ARV programme requires that all components of a functional management system be put in place for effective and efficient functioning. This would include logistics, human resources, financial planning, and monitoring and evaluation systems, as well as sustainable institutional capacities. The Nigerian national ARV treatment training programme was conceived to meet the human resource needs in hospitals providing ARV therapy. This paper reports on the evaluation of the training programme. It examines knowledge and skills gained, and utilisation thereof. Recommendations are made for improved training effectiveness and for specific national policy on training, to meet the demand for scaling up therapy to the thousands who need ARV.

Estimation of the rate of mother to child transmission of HIV in Nigeria.

Definitive diagnosis of HIV infection in infants < 18 months of age who were born to HIV-infected mothers is still posing some difficulty in Nigeria and other developing countries. Within this age definitive diagnosis can only be carried out by antigen based techniques which are indeed not available in these developing countries. This has resulted in the absence of authoritative data on the rate of mother-to-child transmission in these countries. Nigeria inclusive. The present pilot study was therefore carried out to generate some information on the rate of mother to child transmission in Nigeria using the PCR technique. Plasma samples were obtained from 68 children of both sexes less than 18 months of age and who were born to HIV infected mothers. The samples were collected from two pediatric departments. in Lagos and in Benin. The presence of HIV 1 RNA in each of the samples. was determined using the Amplicor Monitor V 1.5 technique (Roche Diagnostics). Data showed that HIV-1 RNA was detected in 15 of the 68 samples tested. This gave an HIV-1 RNA detection rate of 22%. Among women who had some intervention, the rate of transmission of infection was 11% while the rate among those without intervention was 30%. The 22% transmission rate recorded in this study is close to the range of 25 to 35% that has been reported in several developed and a few developing countries. A multicenter nationwide study will still be needed to determine the national mother to child transmission rate in Nigeria.

Potency status and efficacy of measles vaccine administered in Nigeria: a case study of three EPI centres in Lagos, Nigeria.

The potency status and efficacy of measles vaccines were studied in three immunization (EPI) centres in the suburban area of Lagos, Nigeria. A total of 14 vials of measles vaccine were collected and subjected to potency testing while, 203 measles-vaccinated children were recruited for this study. Only 85 (41.87%) of the vaccinees reported back for the post-vaccination follow-up screening. The seroconversion pattern showed that 51(60%) had potent antibody titres ranging from 1:40 to 1:1280, while the remaining 34 (40%) had a low antibody titres between < 1:20 and 1:20. The vaccine potency test showed that only 1 (7.14%) of the 14 vaccine vials collected at these centres had virus titre of 3.5 Log while the remaining 13 (92.86%) had virus titres lower than 3.0 Log: the recommended human dose by the World Health Organisation (WHO) for measles vaccine. The administration of these subpotent and/or impotent vaccines vis-à-vis the status of immune response elicited in the vaccinees may be one of the reasons for the occurrence of measles infection in vaccinated children in the recent time in Nigeria. We herein suggested the subjection of all vaccines to a thorough standard laboratory screening before use in Nigeria.

Faecal contamination level; survival of salmonella typhi and pH changes in 'Gari' and its potential public health hazard in Lagos

The pH changes; faecal contamination level; survival of nalidixic-acid resistant salmonella typhi in 'gari' soaked in water was examined. The pH values showed that 'gari' had a range of pH 3.76 to pH 6.24. The mean pH values showed that there were no appreciable change for gari types from various sources within the studied time period of 120 minutes. Faecal coliform contamination of 4 to 2;400/g using the MPN technique were recorded in 33of the 36 'gari' samples. This high faecal coliform contamination rate of gari; a popular fermented cassava food is unacceptable and it is of public health importance. Our survival experiment showed that the seeded enteric pathogen slightly decreased in colony-forming unit (cfu) with log(0.3 10) 0.3 within the studied 120 minutes. It is concluded that our local foods should be monitored regularly for public health safety; and improved hygienic practices should be emphasized as an intervention for diarrhoeal diseases in developing countries