Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis.

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. It was approved by the United States Federal Drug Administration (US FDA) as an add-on maintenance treatment for patients with severe uncontrolled asthma in December 2021. We conducted a systematic review and meta-analysis to investigate the safety and efficacy of tezepelumab on forced expiratory volume (FEV1) (L), the rate of asthma exacerbations, health-related quality of life, fractional exhaled nitric oxide (FeNO) (ppb), and blood eosinophil count (cells/mL) in patients with severe, uncontrolled asthma. Mean changes for efficacy and proportions (safety) with their corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of six randomized controlled trials comprising 2667 patients were included, of whom 1610 were treated with tezepelumab and 1057 received placebo. The pooled analysis showed that tezepelumab treatment resulted in an improvement in FEV1 of 0.15 L (95% CI: 0.12 to 0.17), a reduction in the asthma exacerbation rate per year of 0.60 (95% CI: 0.51 to 0.70), and a reduction in FeNO of -12.41 ppb (95% CI: -14.28 to -10.53) when compared to placebo. Improvements in FEV1 and FeNO levels were maintained at 24 and 52 weeks. As for safety, patients did not experience a higher incidence of adverse drug reactions with tezepelumab (0.79 (95% CI: 0.55 to 1.12)) as compared to placebo. As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: -0.09 to 0.38) for 70 mg, 0.18 (95% CI: -0.10 to 0.46) for 210 mg, 0.08 (95% CI: -0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV1 with an acceptable safety profile.

Evaluation of clinicians' knowledge of and attitudes to Ebola virus disease in Ebonyi State, Nigeria.

INTRODUCTION: Ebola virus disease (EVD) remains a global threat of international concern. Being at the frontline of medical care, clinicians are at high risk of infection. Inadequate knowledge of, or poor attitudes to, EVD among clinicians may lead to failure in the detection of and timely responses to EVD. We determined the knowledge of and attitudes to EVD among clinicians in Ebonyi State, Nigeria. MATERIALS AND METHODS: A descriptive, cross-sectional study was conducted among clinicians attending an EVD training programme in Ebonyi State, Nigeria. Knowledge and attitudes of the clinicians were evaluated using a structured questionnaire. Data were analysed using descriptive and inferential statistics. RESULTS: Of 398 clinicians who participated in the study, 274 (68.8%) were 40 years and below and 312 (78.4%) were male. Most of the clinicians surveyed (298, 74.9%) had worked for 10 years or less, and 354 (88.9%) of them had not undergone any training on EVD. The overall mean knowledge score of EVD among respondents was 42.0 ± 3.9 (maximum 51), and 370 (93.0%) respondents had a good overall knowledge of EVD. Overall, 334 (83.9%) respondents had an appropriate attitude towards EVD control, while 64 (16.1%) had a poor attitude towards EVD control. Only male gender was an independent predictor of good knowledge of EVD (adjusted odds ratio 4.0, 95% confidence interval 1.8-9.0). CONCLUSIONS: There was generally a high level of knowledge and good attitude to EVD among the clinicians surveyed. The gaps in knowledge and attitudes identified should inform post-EVD control strategies and future training programmes.

Factors Associated with Meeting Current Recommendation for Physical Activity in Scottish Adults with Diabetes.

It remains unclear which factors are instrumental in meeting the recommended physical activity in people with diabetes. We, therefore, aimed to determine the sociodemographic, health-related behavior and clinical factors associated with meeting the recommended levels of physical activity in Scottish adults with diabetes. The study was based on the nationally-representative cross-sectional Scottish Health Surveys (2014-2017). The study participants included a sub-sample of 1259 adults (≥16 years old) with diabetes. Physical activity was evaluated using international guidelines. Overall, 34.1% of the subjects met the recommended levels of physical activity. Independent determinants of meeting the recommended levels of physical activity include male gender (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.07-2.00) and being a non-smoker (OR 1.62; 95% CI 1.02-2.56). Furthermore, meeting the recommended physical activity levels decreased with age (OR 0.96; 95% CI 0.95-0.97), having a longstanding illness (OR 0.56; 95% CI 0.34-0.93) and body mass index (OR 0.94; 95% CI 0.92-0.97), but increased with higher fruit and vegetable intake (OR 1.16; 95% CI 1.07-1.25) and mental wellbeing (OR 1.04; 95% CI 1.02-1.06). Implementation of health promotion programs that target the identified determinants is needed to improve the recommended levels of physical activity among adults with diabetes.

Assessment of community knowledge, attitude, and stigma of Buruli ulcer disease in Southern Nigeria.

BACKGROUND: Poor knowledge can influence timely care-seeking among persons with Buruli ulcer disease (BUD). OBJECTIVES: To assess community knowledge, attitude and stigma towards persons with BUD in endemic settings of Southern Nigeria. METHODS: This was a cross-sectional survey conducted among adult community members in four States of Southern Nigeria. A semi-structured interviewer-administered questionnaire was administered to all participants. RESULTS: Of 491 adults who completed the survey, 315 (64.2%) belonged to the ≤40 years age group, 257 (52.3%) were males and 415 (84.5%) had some formal education. The overall mean (SD) knowledge score was 5.5±2.3 (maximum 10). Only 172 (35.0%) of the participants had a good knowledge of BUD. A total of 327 (66.6%) considered BUD as a very serious illness. Also, there was a high-level of stigma against BUD patients; 372 (75.8%) of the participants felt compassion for and desire to help them, 77 (15.7%) felt compassion but tended to stay away from them, and 53 (10.8%) feared them because they may infect them with the disease. Having a formal education and ethnicity were independent predictors of good knowledge of BUD. CONCLUSION: There is poor community knowledge of BUD in endemic settings of Southern Nigeria which influenced the attitude and perceptions of community members towards persons with BUD.

Widespread arenavirus occurrence and seroprevalence in small mammals, Nigeria.

BACKGROUND: Lassa fever, killing thousands of people annually, is the most reported viral zoonotic disease in Nigeria. Recently, different rodent species carrying diverse lineages of the Lassa virus (LASV) in addition to a novel Mobala-like genetic sequence were detected within the country. Here, screening 906 small mammal specimens from 11 localities for IgG antibodies and incorporating previous PCR detection data involving the same populations, we further describe arenavirus prevalence across Nigeria in relation to host species and geographical location. METHODS: Small mammals were trapped during the period 2011-2015 according to geographical location (endemic and non-endemic zones for Lassa fever), season (rainy and dry seasons between 2011 and 2012 for certain localities) and habitat (indoors, peridomestic settings and sylvatic vegetation). Identification of animal specimens from genera such as Mastomys and Mus (Nannomys) was assisted by DNA sequencing. Small mammals were tested for LASV IgG antibody using an indirect immunofluorescence assay (IFA). RESULTS: Small mammals were infected in both the endemic and non-endemic zones for Lassa fever, with a wider range of species IgG-positive (n = 8) than those which had been previously detected to be PCR-positive (n = 3). IgG-positive species, according to number of infected individuals, were Mastomys natalensis (n = 40), Mastomys erythroleucus (n = 15), Praomys daltoni (n = 6), Mus baoulei (n = 5), Rattus rattus (n = 2), Crocidura spp. (n = 2), Mus minutoides (n = 1) and Praomys misonnei (n = 1). Multimammate mice (Mastomys natalensis and M. erythroleucus) were the most ubiquitously infected, with animals testing positive by either PCR or IgG in 7 out of the 11 localities sampled. IgG prevalence in M. natalensis ranged from 1% in Abagboro, 17-36 % in Eguare Egoro, Ekpoma and Ngel Nyaki, up to 52 % in Mayo Ranewo. Prevalence according to locality, season and age was not, however, statistically significant for M. natalensis in Eguare Egoro and Ekpoma, localities that were sampled longitudinally. CONCLUSIONS: Overall, our study demonstrates that arenavirus occurrence is probably more widely distributed geographically and in extent of host taxa than is currently realized. This expanded scope should be taken into consideration in Lassa fever control efforts. Further sampling should also be carried out to isolate and characterize potential arenaviruses present in small mammal populations we found to be seropositive.

Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016.

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care. Objective: To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016. Design and Setting: We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study. Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates. We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region. We collected data on approval of lenalidomide and bortezomib worldwide. Main Outcomes and Measures: Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year. Results: Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles. The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe. Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016. Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East. In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively. Conclusions and Relevance: Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries. Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa. Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient. Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence.

Evaluation of clinicians' reporting proficiency and their risk perceptions of Ebola virus disease in Ebonyi State, Nigeria.

INTRODUCTION: Ebola virus disease (EVD) is a highly contagious infection with a high case fatality rate. Thus, there is a crucial need for early detection and reporting of any individual suspected to have EVD in order to facilitate containment strategies. The aim of our study was to evaluate clinicians' reporting proficiency and their risk perceptions of EVD in Ebonyi State, Nigeria. METHODS: We performed a descriptive cross-sectional study conducted among clinicians. Consenting clinicians completed a structured questionnaire on the reporting of and their risk perceptions about EVD. Predictors of reporting proficiency and risk perceptions of EVD were identified using multivariable logistic regression analysis. RESULTS: A total of 398 clinicians completed the survey, 312 (78.4%) were male. The average duration of the respondent's clinical practice was 5.0, 8.0, and 8.9 years for those working in primary, secondary and tertiary hospitals, respectively. The overall mean±SD knowledge score for proficiency in reporting was 4.4±0.6 (out of a maximum of 5), and 380 (95.5%) of the respondents had a good knowledge of the modalities of reporting suspected EVD cases. The overall mean±SD risk perception score was 5.6±1.2 (out of a maximum of 10) and only 202 (50.8%) of the respondents had accurate risk estimates towards EVD control. Only male sex was a predictor of accurate risk perception of EVD (aOR 1.7, 95%CI: 1.1-2.9). CONCLUSION: There was a high level of knowledge of reporting modalities regarding EVD among the clinicians; however, only approximately half of them had accurate risk perception towards EVD. The gaps identified should inform post-EVD control strategies.

Prevalence of drug-resistant tuberculosis in Nigeria: A systematic review and meta-analysis.

BACKGROUND: Drug-resistant tuberculosis (TB) undermines control efforts and its burden is poorly understood in resource-limited settings. We performed a systematic review and meta-analysis to provide an up-to-date summary of the extent of drug-resistant TB in Nigeria. METHODS: We searched PubMed, Scopus, Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar for reports published before January 31 2017, that included any resistance, mono-resistance or multidrug resistance to anti-TB drugs in Nigeria. Summary estimates were calculated using random effects models. RESULTS: We identified 34 anti-TB drug resistance surveys with 8002 adult TB patients consisting of 2982 new and 5020 previously-treated cases. The prevalence rate of any drug resistance among new TB cases was 32.0% (95% CI 24.0-40.0%; 734/2892) and among previously-treated cases, the rate was 53.0% (95% CI 35.0-71.0%; 1467/5020). Furthermore, multidrug resistance among new and previously-treated cases was 6.0% (95% CI 4.0-8.0%;161/2502)and 32.0% (95%CI 20.0-44.0; 357/949), respectively. There was significant heterogeneity between the studies (p<0.001, I2 tests). The prevalence of drug-resistant TB varied according to methods of drug susceptibility testing and geographic region of Nigeria. CONCLUSION: The burden of drug-resistant TB in Nigeria is high. We recommend that a national anti-TB drug resistance survey be carried out, and strategies for case detection and programmatic management of drug-resistant TB in Nigeria need to be strengthened.

Secondary bacterial isolates from previously untreated Buruli ulcer lesions and their antibiotic susceptibility patterns in Southern Nigeria.

INTRODUCTION:: Mycolactones, secreted by Mycobacterium ulcerans, were previously believed to prevent super infection in Buruli ulcer lesions. However, little is known about secondary bacterial infections in these lesions. This study evaluated contaminating bacterial flora and their antibiotic susceptibility patterns in cases of previously untreated Buruli ulcer disease from three states in Southern Nigeria. METHODS: A prospective analysis was conducted between January and June of 2015 using wound swabs from eligible patients with Buruli ulcer disease, confirmed by quantitative-polymerase chain reaction, with active ulcers. Microbiological analyses including isolation of bacteria, species identification of isolates, and drug susceptibility tests were performed. RESULTS: Of 51 patients, 27 (52.9%) were female. One or more bacterial species of clinical importance was isolated from each patient. A total of 17 different microbial species were isolated; 76.4% were Gram-negative and 23.6% were Gram-positive isolates. The most common bacterial species detected was Staphylococcus aureus (24%), followed by Aeromonas hydrophila (13%), Pseudomonas aeruginosa (13%), and Klebsiella pneumoniae (11%). Drug susceptibility tests showed a particularly high frequency of resistance to commonly used antimicrobials in Nigeria for Staphylococcus aureus. CONCLUSIONS: Super bacterial infections occur in Buruli ulcer lesions in Nigeria, and these infections are associated with high rates of resistance to commonly used antibiotics in the country.

Secondary bacterial isolates from previously untreated Buruli ulcer lesions and their antibiotic susceptibility patterns in Southern Nigeria

Abstract INTRODUCTION: Mycolactones, secreted by Mycobacterium ulcerans, were previously believed to prevent super infection in Buruli ulcer lesions. However, little is known about secondary bacterial infections in these lesions. This study evaluated contaminating bacterial flora and their antibiotic susceptibility patterns in cases of previously untreated Buruli ulcer disease from three states in Southern Nigeria. METHODS A prospective analysis was conducted between January and June of 2015 using wound swabs from eligible patients with Buruli ulcer disease, confirmed by quantitative-polymerase chain reaction, with active ulcers. Microbiological analyses including isolation of bacteria, species identification of isolates, and drug susceptibility tests were performed. RESULTS Of 51 patients, 27 (52.9%) were female. One or more bacterial species of clinical importance was isolated from each patient. A total of 17 different microbial species were isolated; 76.4% were Gram-negative and 23.6% were Gram-positive isolates. The most common bacterial species detected was Staphylococcus aureus (24%), followed by Aeromonas hydrophila (13%), Pseudomonas aeruginosa (13%), and Klebsiella pneumoniae (11%). Drug susceptibility tests showed a particularly high frequency of resistance to commonly used antimicrobials in Nigeria for Staphylococcus aureus. CONCLUSIONS Super bacterial infections occur in Buruli ulcer lesions in Nigeria, and these infections are associated with high rates of resistance to commonly used antibiotics in the country.

Profile, Outcomes, and Determinants of Unsuccessful Tuberculosis Treatment Outcomes among HIV-Infected Tuberculosis Patients in a Nigerian State.

Background. Few studies have evaluated the rate of tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection and the determinants of its treatment outcomes in Africa. We aimed to determine the predictors of unsuccessful treatment outcomes in HIV-infected tuberculosis patients in Nigeria. Methods. A retrospective cohort study design was used to assess adult TB/HIV patients who registered for TB treatment in two health facilities in Ebonyi State, Southeast Nigeria, between January 2011 and December 2012. Predictors of unsuccessful treatment outcomes were determined using multivariable logistic regression analysis. Results. Of 1668 TB patients, 342 (20.5%) were HIV coinfected. Of these, 195 (57%) had smear-negative pulmonary TB and 11 (3.2%) had extrapulmonary TB. Overall, 225 (65.8%) patients achieved successful outcomes, while 117 (34.2%) had unsuccessful outcomes. The unsuccessful treatment outcomes were due to "default" (9.9%), "death" (19%), "treatment failure" (1.5%), and "transferring out" (3.8%). Independent determinants for unsuccessful outcomes were receiving care at a public facility and noninitiation of antiretroviral therapy. Conclusion. There is need for the reevaluation of the quality of public sector treatment services provided for TB/HIV patients as well as further expansion of TB/HIV collaborative activities in rural areas, and interventions to reduce mortality and default rates among TB/HIV patients are urgently needed in Nigeria.

Household catastrophic payments for tuberculosis care in Nigeria: incidence, determinants, and policy implications for universal health coverage.

BACKGROUND: Studies on costs incurred by patients for tuberculosis (TB) care are limited as these costs are reported as averages, and the economic impact of the costs is estimated based on average patient/household incomes. Average expenditures do not represent the poor because they spend less on treatment compared to other economic groups. Thus, the extent to which TB expenditures risk sending households into, or further into, poverty and its determinants, is unknown. We assessed the incidence and determinants of household catastrophic payments for TB care in rural Nigeria. METHODS: Data used were obtained from a survey of 452 pulmonary TB patients sampled from three rural health facilities in Ebonyi State, Nigeria. Using household direct costs and income data, we analyzed the incidence of household catastrophic payments using, as thresholds, the traditional >10% of household income and the ≥40% of non-food income, as recommended by the World Health Organization. We used logistic regression analysis to identify the determinants of catastrophic payments. RESULTS: Average direct household costs for TB were US$157 or 14% of average annual incomes. The incidence catastrophic payment was 44%; with 69% and 15% of the poorest and richest household income-quartiles experiencing catastrophic activity, respectively. Independent determinants of catastrophic payments were: age >40 years (adjusted odds ratio [aOR] 3.9; 95% confidence interval [CI], 2.0, 7.8), male gender (aOR 3.0; CI 1.8, 5.2), urban residence (aOR 3.8; CI 1.9, 7.7), formal education (aOR 4.7; CI 2.5, 8.9), care at a private facility (aOR 2.9; 1.5, 5.9), poor household (aOR 6.7; CI 3.7, 12), household where the patient is the primary earner (aOR 3.8; CI 2.2, 6.6]), and HIV co-infection (aOR 3.1; CI 1.7, 5.6). CONCLUSIONS: Current cost-lowering strategies are not enough to prevent households from incurring catastrophic out-of-pocket payments for TB care. Financial and social protection interventions are needed for identified at-risk groups, and community-level interventions may reduce inefficiencies in the care-seeking pathway. These observations should inform post-2015 TB strategies and influence policy-making on health services that are meant to be free of charge.

Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases.

Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

Trend in case detection rate for all tuberculosis cases notified in Ebonyi, Southeastern Nigeria during 1999-2009.

Unlike previous annual WHO tuberculosis reports that reported case detection rate for only smear-positive tuberculosis cases, the 2010 report presented case detection rate for all tuberculosis cases notified in line with the current Stop TB strategy. To help us understand how tuberculosis control programmes performed in terms of detecting tuberculosis, there is need to document the trend in case detection rate for all tuberculosis cases notified in high burden countries. This evidence is currently lacking from Nigeria. Therefore, this study aimed to assess the trend in case detection rate for all tuberculosis cases notified from Ebonyi state compared to Nigeria national figures. Reports of tuberculosis cases notified between 1999 and 2009 were reviewed from the Ebonyi State Ministry of Health tuberculosis quarterly reports. Tuberculosis case detection rates were computed according to WHO guidelines. 22, 508 patients with all forms of tuberculosis were notified during the study. Case detection rate for all tuberculosis rose from 27% in 1999 to gradually reach a peak of 40% during 2007 to 2008 before a slight decline in 2009 to 38%. However, the national case detection rate for all tuberculosis cases in Nigeria rose from 7% in 1999 and progressively increased to reach a peak of 19% during 2008 and 2009. Since the introduction of DOTS in Ebonyi, the programme has achieved 40% case detection rate for all tuberculosis cases - about 20% better than national figures. However, with the current low case detection rates, alternative mechanisms are needed to achieve the current global stop- TB targets in Nigeria.

Clinical overlap between malaria and pneumonia: can malaria rapid diagnostic test play a role?

INTRODUCTION: Malaria and pneumonia account for 40% of mortality among children under five years of age in sub-Saharan Africa. Due to lack of diagnostic facilities, their management is based on the integrated management of childhood illnesses (IMCI) strategy. Symptoms of malaria and pneumonia overlap in African children, necessitating dual IMCI classifications at health centres and treatment with both antibiotics and antimalarials. This study determined the prevalence of malaria-pneumonia symptom overlap and confirmed the diagnosis of malaria in these cases using a rapid diagnostic test. METHODOLOGY: Consecutive consultations of 1,216 children (two months to five years old) were documented over a three-month period in a comprehensive health centre. Malaria rapid diagnostic tests were conducted only for children who had symptom overlap. RESULTS: Of the 1,216 children enrolled, 1,090 (90%) reported cough or fever. Among the children fulfilling the malaria case definition, 284 (30%) also met the pneumonia case definition. Twenty-three percent (284) of all children enrolled met the criteria for both malaria and pneumonia. However, only 130 (46%) of them had a positive result for malaria using a malaria rapid diagnostic test. During a malaria-pneumonia overlap, female children (chi-square 5.9, P = 0.01) and children ≥ one year (chi-square 4.8, P = 0.003) were more likely to seek care within two days of fever. CONCLUSION: Dual treatment with antimalarials and antibiotics in children with malaria-pneumonia overlap may result in unnecessary over-prescription of antimalarial medications. Use of rapid diagnostic tests in their management can potentially avoid over-prescribing of malaria medications.