Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2.

Background: Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells. Aim: This study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes. Methods: Neutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes. Results: Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively. Conclusion: The IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19.

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

SARS CoV-2 Seroprevalence in Selected States of High and Low Disease Burden in Nigeria.

Importance: The global impact of COVID-19 has led to an increased need to continuously assess disease surveillance tools. The utility of SARS-CoV-2 serologic tools in determining immunity levels across different age groups and locations in helping to quickly assess the burden of COVID-19 with significant health policy implications is unknown. Objective: To determine the prevalence of SARS-CoV-2 antibodies with respect to the age group and sex of participants. Design, Setting, and Participants: A cross-sectional survey of 4904 individuals across 12 states with high and low COVID-19 disease burden in Nigeria was carried out between June 29 and August 21, 2021. Main Outcomes and Measures: Enzyme-linked immunosorbent assay was used for the detection of specific SARS-CoV-2 immunoglobulin G and immunoglobulin M antibodies, such as the nucleocapsid protein-NCP and spike protein S1. Interviewer-administered questionnaires provided information on participants' history of disease and associated risk factors. Results: A total of 4904 individuals participated in the study (3033 were female [61.8%]; mean [SD] age, 26.7 [6.51] years). A high seroprevalence of SARS-CoV-2 (78.9%) was obtained. Seropositivity was consistent across the states surveyed, ranging from 69.8% in Lagos to 87.7% in Borno. There was no association between sex and seropositivity (female, 2414 [79.6%]; male, 1456 [77.8%]; P = .61); however, an association was noted between age and seropositivity, with the peak prevalence observed in participants aged 15 to 19 years (616 [83.6%]; P = .001). Similarly, loss of appetite (751 [82.3%]; P = .04) and smell (309 [84.4%]; P = .01) were associated with seropositivity. Conclusions and Relevance: In this cross-sectional study, a high SARS-CoV-2 seroprevalence was obtained among the study population during the low level of vaccination at the time of the survey. Thus, there is a need for both an efficacy and antibody neutralization test study to ascertain the efficacy of the antibody detected and the potential for herd immunity in Nigeria.

Gender Variations in Pharmacokinetics of Paracetamol in Hausa/Fulani Ethnic group in Northwest Nigeria - A Two-stage Approach.

BACKGROUND: Paracetamol is one of the most commonly used drugs worldwide and has been linked to drug-related liver damage, even when taken at recommended doses. Ingesting the upper limit of recommended doses of the drug produced a doubling of mortality when compared to not taking the drug. Acetaminophen ingestion has been implicated in the development of angioedema, the exasperation of asthma, and urticaria in patients with aspirin intolerance. AIM: This study aimed at assessing gender variations in the pharmacokinetics of paracetamol in Hausa/Fulani, the most populous ethnic group in Nigeria and determines a possibility of toxicity in the group. METHODS: It was an exploratory study involving twenty participants selected by criterion sampling who satisfied inclusion criteria. They were fasted 11-h preceding acetaminophen administration to 3 h after administration. A single dose of acetaminophen, 1 g orally with 300 ml of distilled water, was administered at 8 A. M. Blood was obtained before the administration and 15, 30, and 45 min, and 1, 2, 3, 4, 5, and 6 h after the administration. Acetaminophen plasma concentrations were determined by validated reverse-phase high-performance liquid chromatography Food and Drug Administration guidelines. RESULTS: Six out of 19 (31.6%) participants have higher than maximum therapeutic plasma concentration (>20 µg/ml). Pharmacokinetics parameters were higher in males except for clearance and volume of distribution. CONCLUSION: Clearance from the plasma tends to be more for females than their male counterparts. A good proportion of Hausa/Fulani is prone to acetaminophen toxicity at a therapeutic dose.

Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021.

BACKGROUND: With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria. METHODS: We conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13. RESULTS: There were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66 121 (18.2%) and 91 644 (20.8%) tested positive in the first and second waves, respectively. There was a 21.3% increase in the number of tests conducted in the second wave with TPR increasing by 14.3%. CI during the first and second waves were 30.3/100 000 and 42.0/100 000 respectively. During the second wave, confirmed COVID-19 cases increased among females and people 30 years old or younger and decreased among urban residents and individuals with travel history within 14 days of sample collection (p value <0.001). Most confirmed cases were asymptomatic at diagnosis during both waves: 74.9% in the first wave; 79.7% in the second wave. CFR decreased during the second wave (0.7%) compared with the first wave (1.8%). CONCLUSION: Nigeria experienced a larger but less severe second wave of COVID-19. Continued implementation of public health and social measures is needed to mitigate the resurgence of another wave.

Assessing the capacity of symptom scores to predict COVID-19 positivity in Nigeria: a national derivation and validation cohort study.

OBJECTIVES: This study aimed to develop and validate a symptom prediction tool for COVID-19 test positivity in Nigeria. DESIGN: Predictive modelling study. SETTING: All Nigeria States and the Federal Capital Territory. PARTICIPANTS: A cohort of 43 221 individuals within the national COVID-19 surveillance dataset from 27 February to 27 August 2020. Complete dataset was randomly split into two equal halves: derivation and validation datasets. Using the derivation dataset (n=21 477), backward multivariable logistic regression approach was used to identify symptoms positively associated with COVID-19 positivity (by real-time PCR) in children (≤17 years), adults (18-64 years) and elderly (≥65 years) patients separately. OUTCOME MEASURES: Weighted statistical and clinical scores based on beta regression coefficients and clinicians' judgements, respectively. Using the validation dataset (n=21 744), area under the receiver operating characteristic curve (AUROC) values were used to assess the predictive capacity of individual symptoms, unweighted score and the two weighted scores. RESULTS: Overall, 27.6% of children (4415/15 988), 34.6% of adults (9154/26 441) and 40.0% of elderly (317/792) that had been tested were positive for COVID-19. Best individual symptom predictor of COVID-19 positivity was loss of smell in children (AUROC 0.56, 95% CI 0.55 to 0.56), either fever or cough in adults (AUROC 0.57, 95% CI 0.56 to 0.58) and difficulty in breathing in the elderly (AUROC 0.53, 95% CI 0.48 to 0.58) patients. In children, adults and the elderly patients, all scoring approaches showed similar predictive performance. CONCLUSIONS: The predictive capacity of various symptom scores for COVID-19 positivity was poor overall. However, the findings could serve as an advocacy tool for more investments in resources for capacity strengthening of molecular testing for COVID-19 in Nigeria.

Evaluation of the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca L Delile in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Balanites aegyptiaca L. Delile (Zygophyllaceae) is a perennial tree that is mostly found in Africa, south Asia and most desert environments. Decoctions of its stem barks are used in northern Nigeria for the treatment of ulcers and stomach issues. Other folkloric uses include treatment of wounds, malaria, dysentery, asthma, and fever. AIM OF THE STUDY: The present study evaluated the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca in Wistar rats. MATERIALS AND METHODS: The antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca (125, 250 and 500 mg/kg, p.o.) was evaluated in ethanol, indomethacin, pylorus ligation and acetic acid-induced ulcer models in rats. Parameters such as mean ulcer indices and percentage ulcer inhibition were assessed in ethanol, indomethacin and acetic acid-induced ulcer models while gastric volume, pH, and titratable acidity were evaluated in the pylorus ligation ulcer model. RESULTS: The extract at the doses of 125, 250 and 500 mg/kg caused a significant (p < 0.01), dose dependent reduction in mean ulcer indices in the ethanol and indomethacin ulcer models. A significant dose dependent reduction in mean ulcer indices were also observed after three (p < 0.01) and seven (p < 0.001) days of treatment with the extract in acetic acid-induced ulcer model. In pylorus ligation model, the gastric secretion parameters (gastric volume, pH, and titratable acidity) showed no alteration in the different doses of the extract when compared to the control. CONCLUSION: Our study showed that the aqueous stem bark extract of Balanites aegyptiaca possesses gastroprotective and ulcer healing properties and therefore not only provides scientific evidence for its folkloric use in the treatment of ulcers but also showed evidence that it may be used in the development of a new phytotherapeutic formulation for the treatment of peptic ulcer.

Attitude of nurses and pharmacists on adverse drug reactions reporting in selected hospitals in Sokoto, Northwest Nigeria.

OBJECTIVE: Objective of this study was to assess the attitude of nurses and pharmacists towards adverse drug reactions (ADRs) reporting. METHODS: The questionnaire was designed based on extended "Inman seven deadly sins." Two hundred and seventy-two respondents were selected by stratified sampling technique. The questionnaires were delivered to the respondents at their places of practice. The data generated were analyzed by Sigma XL Software Inc. FINDINGS: There was no statistically significant relationship between demographic profiles and reporting attitude except for qualification. On extended "Inman seven deadly sins" awareness of reporting protocol and nearby center for ADRs reporting were low 27.3 and 7.5%, respectively. However, respondents' score on components of attitude of ADRs reporting is generally encouraging. On comparative basis, no statistical significance exists between pharmacists and nurses. CONCLUSION: The study showed that attitude of respondents towards ADRs reporting is good. However, there is a need for targeted health education intervention among these cadres of health-care professionals, especially on aspects of awareness of reporting protocol and reporting center.

On the safety of diagnostic ultrasound in pregnancy: have we handled the available data correctly?

Robust evidence of the bioeffects of ultrasound is available from animal studies but human studies are less convincing. Nevertheless, it is disturbing that the only response to safety issues is a twenty-year old principle known as ALARA (As Low As Reasonably Applicable). Using experience from obstetrics and toxicology, and drawing information mainly from two recent systematic reviews and meta-analysis that extensively covered the subject of ultrasound safety, this review captures the current knowledge of ultrasound bioeffects and suggests that it may be time for an international, multidisciplinary meeting on ultrasound safety to decide how to provide the evidence (available data) to patients and sonographers in a succinct manner.

On the Safety of Diagnostic Ultrasound in Pregnancy: Have we Handled the Available Data Correctly?

Robust evidence of the bioeffects of ultrasound is available from animal studies but human studies are less convincing. Nevertheless; it is disturbing that the only response to safety issues is a twenty-year old principle known as ALARA (As Low As Reasonably Applicable). Using experience from obstetrics and toxicology; and drawing information mainly from two recent systematic reviews and meta-analysis that extensively covered the subject of ultrasound safety; this review captures the current knowledge of ultrasound bioeffects and suggests that it may be time for an international; multidisciplinary meeting on ultrasound safety to decide how to provide the evidence (available data) to patients and sonographers in a succinct manner

Ficus platyphylla promotes fertility in female Rattus norvegicus Wistar strain: a preliminary study.

BACKGROUND: Ficus platyphylla Delile (family-Moracea) commonly called gutta percha tree is a deciduous plant found in savannah areas. It grows widely in the Northern part of Nigeria, up to 60 ft. high and is known as 'gamji' by the Hausas. The seeds, bark and leaves have been used traditionally in combination to promote fertility. Scientifically, the plant has been shown to have analgesic, anti-inflammatory and CNS effects. The present study was to validate the use of this plant to promote fertility in female Rattus norvegicus Wistar strain using various fertility parameters. METHODS: Female Rattus norvegicus Wistar strain weighing between 150-180 g were randomly selected and divided into two major groups. Each group was subdivided into 5 treatment groups of 100, 200, 400 mg/kg BW of aqueous extract of F. platyphylla and a control group of 5 ml/kg of distilled water. A positive control of clomiphene citrate was used. Treatment of the first group was discontinued after 15 days prior to mating (pre-mating treatment group), while the other was treated continuously till delivery (continuous treatment group). At the 10th day, females were sacrificed and implantation sites were checked and embryos counted. Upon delivery, litter sizes were determined and the pups weighed and checked for deformities. Other reproductive indices were calculated. Data were analyzed by one-way analysis of variance and students T-test. Proportions were analysed by Chi square. Statistical evaluations were performed using STATS programs and Graphpad prism, and a difference was considered statistically significant at P < 0.05. RESULTS: There was a significant reduction in the percentage post implantation losses of both the pre-treatment and the continuous treatment groups when compared to their distil water controls. The litter size of the pre-treatment group was similar to the distil water group while at 400 mg/kg, the continuous treatment group showed an increase in the litter size similar to that of the clomiphene group. There were no observed external deformities in the pups. CONCLUSIONS: Administration of aqueous extract of F. platyphylla promotes fertility by reducing post implantation loss and by increasing litter size in female Rattus norvegicus Wistar strain.

Knowledge and attitudes of physicians relating to reporting of adverse drug reactions in Sokoto, north-western Nigeria.

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) are important causes of morbidities. Voluntary reporting of ADR is important in safety surveillance of medicines already in the market. This study was, therefore, conducted to appraise the current documentation of ADR in Sokoto, to analyze the extent to which clinicians appreciate factors that could affect reporting ADRs. MATERIALS AND METHODS: Four hospitals within Sokoto metropolis were selected by convenient sampling. Pre-validated questionnaires containing questions on demographic and professional characteristics, and questions that evaluate attitudes as listed in the so-called "deadly sins" of Inman were self-administered by physicians. Data from respondents were analyzed by logistic regression. RESULTS: Of 61 physicians interviewed, 43 (70.5%) had encountered potential ADRs in the 12 months before the study but only 3 (7.0%) of these were reported. Fifty eight (95.1%) of the respondents were not aware that an ADR reporting system was available in Sokoto but all the 3 respondents who were aware of the existence of a reporting system had reported an ADR. Generally, there was no significant relationship between demographic and professional attributes and scores obtained on each of the Inman's attitude measured except that more experienced physicians tend to believe that ADRs are not impossible to identify and female physicians were more reluctant to engage representatives of pharmaceutical companies on ADRs related to their drugs. Additional attitudes that may influence ADRs reporting were identified. CONCLUSION: Adverse drug reactions are under-reported in Sokoto. Lack of physicians' awareness of channels for reporting appears to be the major cause.

Antihyperglycaemic activity of aqueous leaf extract of Combretum micranthum (Combretaceae) in normal and alloxan-induced diabetic rats.

AIM OF THE STUDY: To investigate antidiabetic effect of the leaves of Combretum micranthum G. Don, a medicinal plant used for treating diabetes in Northwestern Nigeria. MATERIALS AND METHODS: Three doses (100mg/kg, 200mg/kg and 400mg/kg) of the aqueous leaf extract of Combretum micranthum were administered to normal glucose loaded, subdiabetic and diabetic rats. RESULTS: Of the doses tested, 100mg/kg of the extract was the most effective. It produces a significant hypoglycaemic and antidiabetic activity comparable to the effect of standard drug (0.6 mg/kg glibenclemide). CONCLUSION: This study demonstrated the potential antidiabetic property of aqueous leaf extract of Combretum micranthum thus justifying its traditional usage.

Artesunate Plus Amodiaquine (AS+AQ) Versus Artemether -Lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Sub-Saharan Africa-A Meta-Analysis.

The purpose of this study is to summarize the available data on the efficacy of Artesunate plus Amodiaquine (AS+AQ) versus Artemether -Lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa using uncorrected parasitaemia as a clinically relevant endpoint. Studies and conference abstracts identified through Pubmed, Medline, Embase, Ansinet, AJOL, Bioline, Cochrane Infectious Diseases Group trials register, The Cochrane Controlled Trials Register, Science Citation Index, Lilacs, African Index Medicus, Clusty, Google, Yahoo and Microsoft search engines. Randomized controlled clinical trials comparing Artesunate-Amodiaquine versus Artemether-Lumefantrine, in Sub-Saharan Africa from January 2004 to June 2009, and which had at least 30 patients per study arm. The authors independently applied the inclusion criteria, assessed methodological quality and extracted data into a predesigned form. The outcome of interest was uncorrected day 28 parasitological failure. Data were then checked for agreement and double entered into RevMan version 5 for further analyses. Fifteen trials (4265 participants) met the inclusion criteria. Day 28 parasitological failure was lower for AL (286 of 2201 participants or 13.0 % failures) when compared with AS+AQ (446 of 2424 participants or 18.4% failures). The relative risk of parasitological failure with AS+AQ was higher when compared with AL (RR 1.65, 95% CI, 1.18-2.32). There were significant heterogeneity and inconsistencies in the studies. AL appears more effective at avoiding parasitological failure at days 28 than AS+AQ.

Is chloroquine better than artemisinin combination therapy as first line treatment in adult nigerians with uncomplicated malaria?-A cost effectiveness analysis.

The current case management and drug policy of malaria in Nigeria recommended by the Federal ministry of health may not be appropriate for all age categories. This suspicion was tested by running a cost effectiveness analysis of two possible and alternative strategies: Artemisinin Combination Therapy (ACT) or Chloroquine and ACT only if CQ fails (CANACT), in adult non pregnant Nigerians aged 20-45yrs. The result confirms that ACT is indeed more effective but also more costly with an incremental cost effectiveness ratio (ICER) of #2,546,527.00 per QALY that is much higher than the estimated upper limit of #25,000.00 that either patients or provider may be willing to pay. The CANACT strategy may be the most cost effective strategy in this subgroup of Nigerian patients and also provides better value for money.

Dose-dependent amelioration of gentamicin-Induced nephrotoxicity in adult swiss albino rats by vitamin B-complex - A preliminary study

Purpose: To evaluate the effect of vitamin B-complex on the nephrotoxicity of gentamicin in an established rat model. Methods: Adult Swiss albino rats weighing 170±20g were divided into 4 groups of 4 rats each. Each group was given one of the following: placebo injection (Control), 80mg/kg of gentamicin sulphate alone or with 1.5ml/kg/3ml/kg body weight of vitamin B-complex (intramuscular) containing 10mg thiamine, 1.5mg riboflavin and 1.0mg pyridoxal-6-phosphate per ml. Results: In the Swiss albino rats, daily intramuscular 80mg/kg gentamicin sulphate significantly (p<0.05) and consistently produced biochemical signs of nephrotoxicity after 5 days. Also, 1.5 ml/kg of B-complex significantly (p<0.05) ameliorated the rate and extent of increase in serum urea and creatine while 3ml/kg of the same drug completely prevented the increase in serum urea and creatine in this model. Conclusion: Vitamin B-complex dose-dependently ameliorated gentamicin-induced nephrotoxicity in adult Swiss albino rats when given intramuscularly. This finding may have important clinical utility