Sickle cell trait, APOL1 risk allele status and chronic kidney disease among ART-experienced adults living with HIV in northern Nigeria.

BACKGROUND: We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 (APOL1) risk variants in people living with HIV (PLWH) in Nigeria, and to establish if SCT and APOL1 high-risk status correlate with estimated glomerular filtration rate (eGFR) and/or prevalent chronic kidney disease (CKD). METHODS: Baseline demographic and clinical data were obtained during three cross-sectional visits. CKD was defined as having an eGFR<60 mL/min/1.73 m2. We collected urine specimens to determine urine albumin-creatine ratio and blood samples for sickle cell genotyping, APOL1 testing, and for creatinine/cystatin C assessment. The associations between SCT, APOL1 genotype, and eGFR/CKD stages/CKD were investigated using linear/ordinal logistic/logistic regression models, respectively. RESULTS: Of 2443 participants, 599 (24.5%) had SCT, and 2291 (93.8%) had a low-risk APOL1 genotype (0 or 1 risk variant), while 152 (6.2%) had high-risk genotype (2 allele copies). In total, 108 participants (4.4%) were diagnosed with CKD. In adjusted analyses, SCT was associated with lower eGFR (adjusted mean difference [aMD]= -2.33, 95% CI -4.25, -0.42), but not with worse CKD stages, or increased odds of developing CKD. Participants with the APOL1 high risk genotype were more likely to have lower eGFR (aMD= -5.45, 95% CI -8.87, -2.03), to develop CKD (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.03, 3.75), and to be in worse CKD stages (aOR = 1.60, 95% CI: 1.12, 2.29) than those with the low-risk genotype. There was no evidence of interaction between SCT and APOL1 genotype on eGFR or risk of CKD. CONCLUSION: Our findings highlight the multifaceted interplay of genetic factors in the pathogenesis of CKD in PLWH.

Training the next generation of Biostatisticians in West Africa: The Vanderbilt Nigeria Biostatistics Training Program (VN-BioStat).

Biomedical HIV research is growing in West Africa, but biostatistical expertise is lagging. The Vanderbilt-Nigeria Biostatistics Training Program (VN-BioStat) seeks to establish a research and training platform for biostatisticians doing HIV-related research in Nigeria. The objectives of the program are: 1) Host two Nigerian data scientists per year (a total of 10 over 5 years) at Vanderbilt University Medical Center to gain hands-on biostatistics training and experience via one-year fellowships. Eligible trainees will be junior investigators with PhDs or nearing completion of their PhDs in statistics or related fields, including mathematics and computer science. 2) Conduct annual workshops in Nigeria to provide biostatistics training. Trainees will undertake biostatistics coursework and hands-on training and participate in mentorship as biostatisticians involved in HIV research. Trainees will be at Vanderbilt for a full year and be part of an active biostatistics department. They will be immersed in a dry-lab HIV biostatistics project in collaboration with a Nigerian HIV research project and lead a methodologically focused research project. They will also participate in a one-month research training/grant writing program in Nashville. The VN-BioStat program will build on the existing momentum of ongoing initiatives to enhance research capacity in Nigeria by developing biostatistics leadership. VN-BioStat trainees will interact with investigators from Nigeria to provide collaborative biostatistical assistance with study design and data analysis, thus gaining real-world experience that will benefit the trainees and the broader research community in Nigeria.

Barriers and Facilitators of Premarital Genetic Counseling for Sickle Cell Disease in Northern Nigeria.

In high-income countries, premarital genetic counseling for Sickle Cell Disease (SCD) is a standard practice. However, in Nigeria, there is no formal premarital genetic counseling program available for SCD. We conducted a series of focus group discussions with health care professionals, patients with SCD, and parents of the patients with or without SCD to gain an understanding of their attitudes and beliefs towards SCD/Sickle Cell Trait and premarital genetic counseling for SCD. Data were analyzed using Charmaz's constructivist grounded theory approach. Two themes were highlighted in the analysis as follows: (1) the difference between the perception of premarital sickle cell screening among individuals with SCD versus the general population, and (2) the personal beliefs and physical challenges that could lead to the avoidance of premarital screening within the general community. Lack of disease-related knowledge, testing facilities, transportation, and stigma associated with the disease were the most commonly perceived barriers to premarital testing. Also, a willingness to receive premarital testing for SCD exists within our community to reduce the spread of the disease and advocate for improved health-related quality of life of patients with SCD. The content and structure of a premarital genetic counseling program in Kano, Northern Nigeria, needs to be developed.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

The Vanderbilt Nigeria Biostatistics Training Program (VN-BioStat): Results from a Skills Workshop.

The Vanderbilt-Nigeria Biostatistics Training Program (VN-BioStat) aims to establish a research and training platform for biostatisticians doing HIV-related research in Nigeria, including enhancing mid-level biostatistics capacity through annual workshops. This paper describes findings from the inaugural workshop in Kano, Nigeria. Participants were surveyed before and after the workshop to assess their self-perceived familiarity with and confidence in their abilities to use statistical software and apply specific statistical techniques, as well as to gather feedback regarding the conduct of the workshop and future topic areas. Of the 23 participants enrolled in the workshop, 22 (96%) completed both pre- and post-workshop assessments. In both pre-workshop and post-workshop surveys, participants ranked their confidence in statistical skills using Likert scales. Scores were transformed to a 0-100 scale, and averages computed. Participants also shared open-ended feedback about the workshop and suggested future topic areas. Before the training, the average participant reported having either a "beginner" (30% of participants) or "moderate" (43%) level of familiarity with R. Many participants (65%) rated themselves as having "moderate" or "expert" familiarity with SPSS. Pre-workshop averages for confidence ranged from 26 to 64, with lowest confidence in "expanding continuous covariates in regression models and interpret results" and highest confidence in "fitting and interpreting results from a linear regression model". Post-workshop averages for confidence were all above 70. The lowest post-workshop score (74) was for "fit and interpret results from a semiparametric linear transformation model". The greatest increase in confidence was observed in "expanding continuous covariates in regression models using splines and interpreting results" and the lowest increase was in "fitting and interpreting results from a linear regression model." Participants offered positive feedback on instructor effectiveness (4.9/5) and overall course quality (4.9/5). While the overall course was rated on a 0-100 scale as "moderately difficult" (mean ± SD: 40.5 ± 17.5), the participants felt the course was highly organized (87.7 ± 17.8), and the information was moderately easy to learn (81.9 ± 15.9). Suggestions for future workshops included providing supplementary resources for out-of-classroom learning and releasing codes in advance to enhance participants' preparation. Among suggestions for future workshop topics, 80% of respondents listed survival analysis. Lessons learned provide insight into how short-term training opportunities can be leveraged to build biostatistics capacity in similar settings.

Transmission Dynamics of Monkeypox Virus in Nigeria during the Current COVID-19 Pandemic and Estimation of Effective Reproduction Number.

Monkeypox virus (MPXV) continues to pose severe threats to global public health, especially in non-endemic areas. Like all other regions, Africa faces potential public health crises due to the ongoing COVID-19 pandemic and other infectious disease outbreaks (such as Lassa fever and malaria) that have devastated the region and overwhelmed the healthcare systems. Owing to the recent surge in the MPXV and other infections, the COVID-19-control efforts could deteriorate and further worsen. This study discusses the potential emergencies of MPXV transmission during the current COVID-19 pandemic. We hypothesize some of the underlying drivers that possibly resulted in an increase in rodent-to-human interaction, such as the COVID-19 pandemic's impact and other human behavioral or environmental factors. Furthermore, we estimate the MPXV time-varying effective reproduction number (Rt) based on case notification in Nigeria. We find that Rt reached a peak in 2022 with a mean of 1.924 (95% CrI: 1.455, 2.485) and a median of 1.921 (95% CrI: 1.450, 2.482). We argue that the real-time monitoring of Rt is practical and can give public health authorities crucial data for circumstantial awareness and strategy recalibration. We also emphasize the need to improve awareness programs and the provision of adequate health care resources to suppress the outbreaks. These could also help to increase the reporting rate and, in turn, prevent large community transmission of the MPXV in Nigeria and beyond.

The Heterogeneous Severity of COVID-19 in African Countries: A Modeling Approach.

The COVID-19 pandemic has had a considerable impact on global health and economics. The impact in African countries has not been investigated thoroughly via fitting epidemic models to the reported COVID-19 deaths. We downloaded the data for the 12 most-affected countries with the highest cumulative COVID-19 deaths to estimate the time-varying basic reproductive number ([Formula: see text]) and infection attack rate. We develop a simple epidemic model and fitted it to reported COVID-19 deaths in 12 African countries using iterated filtering and allowing a flexible transmission rate. We observe high heterogeneity in the case-fatality rate across the countries, which may be due to different reporting or testing efforts. South Africa, Tunisia, and Libya were most affected, exhibiting a relatively higher [Formula: see text] and infection attack rate. Thus, to effectively control the spread of COVID-19 epidemics in Africa, there is a need to consider other mitigation strategies (such as improvements in socioeconomic well-being, healthcare systems, the water supply, and awareness campaigns).

Control of snakebite envenoming: A mathematical modeling study.

A mathematical model is designed to assess the impact of some interventional strategies for curtailing the burden of snakebite envenoming in a community. The model is fitted with real data set. Numerical simulations have shown that public health awareness of the susceptible individuals on snakebite preventive measures could reduce the number of envenoming and prevent deaths and disabilities in the population. The simulations further revealed that if at least fifty percent of snakebite envenoming patients receive early treatment with antivenom a substantial number of deaths will be averted. Furthermore, it is shown using optimal control that combining public health awareness and antivenom treatment averts the highest number of snakebite induced deaths and disability adjusted life years in the study area. To choose the best strategy amidst limited resources in the study area, cost effectiveness analysis in terms of incremental cost effectiveness ratio is performed. It has been established that the control efforts of combining public health awareness of the susceptible individuals and antivenom treatment for victims of snakebite envenoming is the most cost effective strategy. Approximately the sum of US$72,548 is needed to avert 117 deaths or 2,739 disability adjusted life years that are recorded within 21 months in the study area. Thus, the combination of these two control strategies is recommended.

The co-circulating transmission dynamics of SARS-CoV-2 Alpha and Eta variants in Nigeria: A retrospective modeling study of COVID-19.

BACKGROUND: The COVID-19 pandemic poses serious threats to public health globally, and the emerging mutations in SARS-CoV-2 genomes has become one of the major challenges of disease control. In the second epidemic wave in Nigeria, the roles of co-circulating SARS-CoV-2 Alpha (ie, B.1.1.7) and Eta (ie, B.1.525) variants in contributing to the epidemiological outcomes were of public health concerns for investigation. METHODS: We developed a mathematical model to capture the transmission dynamics of different types of strains in Nigeria. By fitting to the national-wide COVID-19 surveillance data, the transmission advantages of SARS-CoV-2 variants were estimated by likelihood-based inference framework. RESULTS: The reproduction numbers were estimated to decrease steadily from 1.5 to 0.8 in the second epidemic wave. In December 2020, when both Alpha and Eta variants were at low prevalent levels, their transmission advantages (against the wild type) were estimated at 1.51 (95% credible intervals (CrI) = 1.48, 1.54), and 1.56 (95% CrI = 1.54, 1.59), respectively. In January 2021, when the original variants almost vanished, we estimated a weak but significant transmission advantage of Eta against Alpha variants with 1.14 (95% CrI = 1.11, 1.16). CONCLUSIONS: Our findings suggested evidence of the transmission advantages for both Alpha and Eta variants, of which Eta appeared slightly more infectious than Alpha. We highlighted the critical importance of COVID-19 control measures in mitigating the outbreak size and relaxing the burdens to health care systems in Nigeria.

Men with sickle cell disease experience greater sexual dysfunction when compared with men without sickle cell disease.

Recurrent ischemic priapism is a common complication of sickle cell disease (SCD). We assessed the burden, characteristics, and types of priapism, including sexual dysfunction, in a cohort of men with and those without SCD, to test the hypothesis that sexual dysfunction is more prevalent in men with SCD. In Kano, Nigeria, we conducted a comparative cross-sectional survey that included 500 and 250 men 18 to 40 years of age, with and without SCD, respectively. The survey used the Priapism Questionnaire and the International Index of Erectile Function for sexual function assessment. All eligible participants approached for the study gave informed consent and were enrolled. Stuttering and major priapism were defined based on the average duration of priapism experiences that lasted ≤4 and >4 hours, respectively. The prevalence of priapism was significantly higher in men with SCD than in those without it (32.6% vs 2%; P < .001). Stuttering priapism accounted for 73.6% of the priapism episodes in men with SCD. Nearly 50% of the participants with SCD-related priapism had never sought medical attention for this complication. The majority of the men with SCD-related priapism used exercise as a coping mechanism. Priapism affected the self-image of the men with SCD, causing sadness, embarrassment, and fear. The percentage of the men with SCD who had erectile dysfunction was more than twofold higher than that of those without SCD who had erectile dysfunction (P = .01). The men with SCD had a higher prevalence of priapism and sexual dysfunction than the men without SCD.

Mathematical analysis of a model for zoonotic visceral leishmaniasis.

Zoonotic visceral leishmaniasis (ZVL), caused by the protozoan parasite Leishmania infantum and transmitted to humans and reservoir hosts by female sandflies, is endemic in many parts of the world (notably in Africa, Asia and the Mediterranean). This study presents a new mathematical model for assessing the transmission dynamics of ZVL in human and non-human animal reservoir populations. The model undergoes the usual phenomenon of backward bifurcation exhibited by similar vector-borne disease transmission models. In the absence of such phenomenon (which is shown to arise due to the disease-induced mortality in the host populations), the nontrivial disease-free equilibrium of the model is shown to be globally-asymptotically stable when the associated reproduction number of the model is less than unity. Using case and demographic data relevant to ZVL dynamics in AracÌ£atuba municipality of Brazil, it is shown, for the default case when systemic insecticide-based drugs are not used to treat infected reservoir hosts, that the associated reproduction number of the model (ℛ0) ranges from 0.3 to 1.4, with a mean of ℛ0=0.85 . Furthermore, when the effect of such drug treatment is explicitly incorporated in the model (i.e., accounting for the additional larval and sandfly mortality, following feeding on the treated reservoirs), the range of ℛ0 decreases to ℛ0∈[0.1,0.6] , with a mean of ℛ0=0.35 (this significantly increases the prospect of the effective control or elimination of the disease). Thus, ZVL transmission models (in communities where such treatment strategy is implemented) that do not explicitly incorporate the effect of such treatment may be over-estimating the disease burden (as measured in terms of ℛ0 ) in the community. It is shown that ℛ0 is more sensitive to increases in sandfly lifespan than that of the animal reservoir (so, a strategy that focuses on reducing sandflies, rather than the animal reservoir (e.g., via culling), may be more effective in reducing ZVL burden in the community). Further sensitivity analysis of the model ranks the sandfly removal rate (by natural death or by feeding from insecticide-treated reservoir hosts), the biting rate of sandflies on the reservoir hosts and the progression rate of exposed reservoirs to active ZVL as the three parameters with the most effect on the disease dynamics or burden (as measured in terms of the reproduction number ℛ0 ). Hence, this study identifies the key parameters that play a key role on the disease dynamics, and thereby contributing in the design of effective control strategies (that target the identified parameters).