Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.

INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.

High prevalence of resistance to third-generation cephalosporins detected among clinical isolates from sentinel healthcare facilities in Lagos, Nigeria.

BACKGROUND: Antimicrobial resistance (AMR) in bacterial pathogens is a worldwide concern that demands immediate attention. Most information on AMR originates from high-income countries and little is known about the burden in Africa, particularly Nigeria. Using four sentinel sites (General hospitals) in Lagos State, this study sought to estimate the burden of AMR. METHODS: This is a hospital-based surveillance using secondary health care centres. Four sites were randomly selected and included in the study. Clinical isolates were collected over a period of 6 months for each site from August 2020 to March 2021. All isolates were characterised and analysed for resistance to 15 antibiotics using the Kirby-Baur method. Multiplex PCR assay was used for the detection of Extended spectrum beta lactamase genes. Data analysis was done using SPSS version 27.0. RESULTS: Four hundred and ninety-nine (499) patients consented and participated in this study, consisting of 412 (82.6%) females and 87 (17.4%) males. The mean age ± SD of the participants was 33.9 ± 13.8 with a range of 1-89 years. The majority (90.8%) of the participants were outpatients. Two hundred and thirty-two (232) isolates were obtained from 219 samples, comprising of 120 (51.7%) Gram positive and 112 (48.3%) Gram negative organisms. Key bacterial pathogens isolated from this study included Staphylococcus aureus (22.8%), Escherichia coli (16.4%), Staphylococcus spp. (15.9%), Enterococcus spp. (7.3%) and Klebsiella pneumoniae (6.5%). There was high prevalence of multi-drug resistance (79.3%) among the isolates with 73.6% of Staphylococcus aureus phenotypically resistant to methicillin and 70% possessed the MecA gene. 76.5% of Enterococcus spp. isolated were Vancomycin resistant. Overall, resistance to Cephalosporins was most frequently/commonly observed (Cefotaxime 87.5%). CONCLUSION: A high incidence of AMR was identified in clinical bacteria isolates from selected general hospitals in Lagos State, highlighting the necessity for the implementation of national action plans to limit the prevalence of AMR. Surveillance via collection of isolates has a lot of promise, especially in resource-limited environments.

A national survey of public awareness of antimicrobial resistance in Nigeria.

BACKGROUND: One of the objectives of the Global Action Plan by the World Health Organization (WHO) to contain antimicrobial resistance (AMR), is to improve global awareness through effective communication and education. Comprehensive information on the level of awareness of AMR among Nigerian public is deficient. This study was therefore designed to assess the current level of awareness and knowledge of the Nigerian public of AMR. METHODS: Pre-tested and validated questionnaire was used to obtain information from the general public across the six geopolitical zones (North Central, North East, North West, South East, South South and South West) in Nigeria. Multi-stage sampling was used to select one state from each zone and respondents were selected through a multi-stage sampling technique. Responses to eight questions were used to grade the level of knowledge categorized as poor, fair and good. Collation and analysis of data were performed at the Microbiology Department of the Nigerian Institute of Medical Research (NIMR), Lagos, Nigeria, using SPSS version 24.0. RESULTS: Questionnaires from 482 respondents comprising 242 (50.2%) females and 240 (49.8%) males from six states (Lagos, Ebonyi, Delta, Plateau, Borno and Jigawa) were analyzed. Of the 482 respondents, 322 (66.8%) had taken antibiotics in the last six months out of which 31.3% were without prescription. 26.1% of respondents believe they don't need to complete the dosage as long as they feel better. Although 272(56.5%) of the respondents were familiar with the term "antibiotic resistance", only 40(8.3%) had good knowledge of AMR. A majority (76.6%) believed that they were powerless to stop the spread of AMR. There was no association between the gender of respondents and knowledge of AMR (p = 0.13). However, respondents from Ebonyi and Delta states in southern Nigeria were more likely to have good knowledge of AMR (X2 = 53.22, P < 0.0001). The respondents in the urban area had a higher score for knowledge level compared to the rural dwellers, though this was not statistically significant within and across states. CONCLUSION: This survey provides an insight into the level of AMR awareness and antibiotic use in the wider Nigeria public. Our findings show that about a third of the general public consume antibiotics obtained without prescription. There is an overall poor understanding of antimicrobial resistance and/or proper use of antibiotics among respondents. It is critical that more holistic public enlightenment programs are carried out to increase awareness of AMR and promote responsible use of antibiotics.

A FOUR-YEAR REVIEW OF GERIATRIC MENTAL HEALTH SERVICES. IN A LAGOS BASED HOSPITAL, NIGERIA

Background: There is a growing global concern about the public health implications of the increasing population of the elderly. One main issue of concern is centered on how to address their mental health needs using homegrown interventions and services. We expect that important lessons on geriatric mental health issues would be brought to fore in this report. Methods: This is a four-year (2007-2011) retrospective report on the mental health services rendered to 938 clients aged 60 years and above at a Lagos based mental health treatment facility in Nigeria. Designed questionnaires were filled with socio-demographic and clinical data obtained from patients case notes based on the objectives of the study. Results: The mean (standard deviation) age of elders was (±7.93) 69.6 years, and 65.5% were females. Majority were married, self-employed and belonged to low socio-economic status (73.1%, 63.1% and 63.2%, respectively). Close to two-thirds (62.4%) commute for at least one hour to get treatment. The commonest diagnosis was psychotic disorders (34.8%), while 5.5% had Alzheimer's dementia. Some 96.5% of the elders were solely on medications. About a quarter had past history of mental illness and 48.5% reported co-morbid medical conditions, with cardiovascular problems (53.0%) being the commonest physical comorbidity. The middle old along with very old elders (aged≥70 years), and those with at least tertiary education, were more likely to present with dementia were more likely to present with index episode of mental illness and receive outpatient care Conclusion: The elders were managed for a wide range of treatable mental illnesses and other comorbidities and commute for hours to access care. Pharmacotherapy was the preponderant sole treatment modality. There is need for sustained development of expertise to enhance multimodal care and scaling up of comprehensive geriatric mental health services. Further research is needed on how to appropriately link and/or integrate geriatric care with services at all-tiers of health care delivery.

A four-year review of geriatric mental health services in a Lagos based hospital, Nigeria

Background: There is a growing global concern about the public health implications of the increasing population of the elderly. One main issue of concern is centered on how to address their mental health needs using home-grown interventions and services. We expect that important lessons on geriatric mental health issues would be brought to fore in this report.Methods: This is a four-year (2007-2011) retrospective report on the mental health services rendered to 938 clients aged 60 years and above at a Lagos based mental health treatment facility in Nigeria. Designed questionnaires were filled with socio-demographic and clinical data obtained from patients' case notes based on the objectives of the study.Results: The mean (standard deviation) age of elders was 69.6 (±7.93) years, and 65.5% were females. Majority were married, self-employed and belonged to low socio-economic status (73.1%, 63.1% and 63.2%, respectively). Close to two-thirds (62.4%) commute for at least one hour to get treatment. The commonest diagnosis was psychotic disorders (34.8%), while 5.5% had Alzheimer's dementia. Some 96.5% of the elders were solely on medications. About a quarter had past history of mental illness and 48.5% reported co-morbid medical conditions, with cardiovascular problems (53.0%) being the commonest physical comorbidity. The middle old along with very old elders (aged ≥70years), and those with at least tertiary education, were more likely to present with dementia. Elders with dementia were more likely to present with index episode of mental illness and receive outpatient care.Conclusion: The elders were managed for a wide range of treatable mental illnesses and other comorbidities and commute for hours to access care. Pharmacotherapy was the preponderant sole treatment modality. There is need for sustained development of expertise to enhance multimodal care and scaling up of comprehensive geriatric mental health services. Further research is needed on how to appropriately link and/or integrate geriatric care with services at all-tiers of health care delivery

From addiction to infection: managing drug abuse in the context of HIV/AIDS in Africa.

People who use drugs are at higher risk of HIV: directly through the sharing of injecting equipment, indirectly through associated risk behavior, and physiologically through the substances' impact on the immune system. Drug users, especially people who inject drugs (PWID) are a bridge to the general population. The treatment of drug addiction and provision of harm reduction interventions have impact on HIV transmission and incidence. Addiction treatment reduces the frequency of drug-related risky behaviors and enhances access and adherence to HIV treatment, resulting in fewer new infections. However, the drug policies of many African countries are punitive and hostile to harm reduction programs. These fuel criminalization of drug use and discrimination against the drug user thereby preventing individuals with drug addiction from accessing treatment programs. There is need to formulate policies aimed at protecting the rights of people with drug addiction and address the ethical aspects of treatment.

Psychiatric emergencies and the millennium: an international study.

BACKGROUND: The millennium posed an unknown challenge to mental health services worldwide. In anticipation, contingencies were implemented in preparation for the unexpected impact on psychiatric morbidity. RESULTS: This study evaluates the impact of the millennium on psychiatric emergency service utilization in the Northern and Southern hemispheres--the UK, Nigeria and Australia. Findings did not demonstrate a notable "millennium effect" on mental health services. A number of patients presented psychopathology incorporating millennium themes. A post-Christmas and post-New Year increase in presentation was observed. CONCLUSION: There was no change in service needs.