Heart failure in Nigeria: protocol for a systematic review and meta-analysis.

Background: Heart failure is now a significant contributor to the burden of non-communicable diseases in developing countries like Nigeria which is experiencing epidemiologic and demographic transition. The epidemiology of heart failure in this country is poorly characterized. The aim of the review is to determine the prevalence of heart failure, the associated risk factors, the aetiology, management, and outcomes of the condition in the country. Methods: Relevant databases such as PubMed /Medline, EMBASE, Web of Science, Google Scholar, African Index Medicus, and African journal online would be searched for articles published in English from January 2000 to December 2021. The analysis will include observational studies conducted among Nigerian adults aged 12 years and above. Article selection shall be conducted by pairs of independent reviewers. Data extraction shall be done by 2 independent reviewers. Results: The primary outcome would be the pooled prevalence of heart failure while the secondary outcomes would be to identify the risk factors and management of heart failure in Nigeria. Conclusion: This will be the first systematic review and meta-analysis of heart failure epidemiology in Nigeria which will hopefully identify gaps for future research and guidance for policy interventions.

Cohort study on adverse drug reactions in adults admitted to the medical wards of a tertiary hospital in Nigeria: Prevalence, incidence, risk factors and fatality.

AIMS: Intensive monitoring of medical patients for adverse drug reactions (ADRs) to assess prevalence, incidence, risk factors and fatality of ADRs leading to hospital admission or occurring in the hospital. METHODS: Prospective cohort study on 1280 adult patients admitted to the medical wards of a tertiary institution over 12 months. Patients were assessed for ADRs during and throughout admission; causality and preventability of ADRs were assessed. RESULTS: Sixty-seven (5.2%) patients had ADRs, 51 (3.9%) caused hospitalisation while 17(1.3%) occurred during hospitalisation, and 42 (62.7%) of total ADRs were preventable. Nonsteroidal anti-inflammatory drugs, 14 (20.3%), antidiabetics, 12 (17.4%) and antibacterial, 11 (15.8%) were the most implicated drug classes. Gastrointestinal tract (37%), central nervous system (30.2%), and skin (24.7%) were the most affected organ/systems, while upper gastrointestinal bleeding and hypoglycaemia were the most observed ADRs. ADRs led to deaths in 7 (10.4%) patients, with an overall case fatality rate of 0.5%. The highest number of deaths were among patients with Stevens-Johnson syndrome 2/7 (28.6%) and hepatotoxicity 2/7 (28.6%). Risk factors, adjusted odds ratio (AOR [95% confidence interval, CI]) for ADRs leading to hospitalisation was male sex 3.11 (1.11, 8.73) while for ADRs during hospitalisation were number of drugs used before admission (AOR [95% CI] = 6.67 [1.16, 38.47]) and comorbidities (AOR [95% CI] = 3.0 [1.13, 8.01]). Patients admitted with ADRs had prolonged hospital stay (AOR [95% CI] = 3.37 [1.11, 8.71]). CONCLUSION: Preventable ADRs are common and important causes of hospitalisation and inpatients' morbidity and mortality among medical patients in Nigeria. Upper gastrointestinal bleeding and hypoglycaemia, resulting from nonsteroidal anti-inflammatory drugs and antidiabetic drugs were the most observed ADRs.

Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents.

Hearing loss is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342 GJB2 mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala, and the United States (South Florida). We detected causative DNA variants in 25 % of multiplex and 7 % of simplex families. The detection rate varied between 0 and 57 % based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include MYO15A, SLC26A4, USH2A, MYO7A, MYO6, and TRIOBP. Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.

Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.

Asymptomatic falciparum malaria and genetic polymorphisms of Pfcrt K76T and Pfmdr1 N86Y among almajirai in northeast Nigeria.

INTRODUCTION: Malaria remains a public health challenge, especially in sub-Saharan Africa where asymptomatic malaria is not uncommon. In the present study, the prevalence of asymptomatic falciparum malaria was investigated in almajirai, and the genetic polymorphisms of chloroquine (CQ) resistance biomarkers were assessed. METHODOLOGY: A total of 440 apparently healthy almajirai between 3 and 12 years of age were randomly enrolled in Maiduguri, northeast Nigeria, between July and December 2010. Parasitemia and gametocytemia were assessed by light microscopy, and polymorphisms of Pfcrt K76T and Pfmdr1 N86Y were detected by nested polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. RESULTS: The mean age of the subjects was 8.3 ± 4.5 years, with subjects ≤ 5 years accounting for 10.7% (47/440) of the population. Prevalence of asymptomatic falciparum parasitemia and gametocytemia were 12.7% (56/440) and 8.6% (38/440), respectively. Geometric mean parasite density (GMPD) was 240 (160-630) parasites/µL, while geometric mean gametocyte density (GMGD) was 53 (24-96) gametocytes/µL. The GMPD was higher among subjects ≤ 5 years of age (p = 0.027). Pfcrt 76T was detected in 5.4% (3/56) of the isolates, and no isolates harbored Pfmdr1 86Y mutant. CONCLUSIONS: The study reveals asymptomatic falciparum malaria in almajirai and low levels of Pfcrt 76T and Pfmdr1 86Y alleles. These findings could hinder malaria control measures, and hence almajirai should be incorporated into malaria control programs.

Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.

OBJECTIVES: Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug-drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). METHODS: This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n = 10) and ART-naive subjects (control group, n = 11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. RESULTS: Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC0₋24 145 versus 204 ng·h/mL, P = 0.02; DEAQ AUC0₋96 14,571 versus 21,648 ng·h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) ratio was not different between groups (ART group 116 versus control group 102, P = 0.67). CONCLUSIONS: Subjects on nevirapine-based ART had lower exposure to both amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected individuals on this ART combination.