Lassa fever (LF) remains endemic in Nigeria with the country reporting the highest incidence and mortality globally. Recent national data suggests increasing incidence and expanding geographic ...spread. Predictors of LF case positivity in Nigeria have been sparsely studied. We thus sought to determine the sociodemographic and clinical determinants of LF positivity amongst suspected cases presenting to health facilities from 2018 to 2021. A secondary analysis of the national LF surveillance data between January 2018 and December 2021. Socio-demographic and clinical data of 20,027 suspected LF cases were analysed using frequencies and Chi-square statistics with significant p-value set at p < 0.05. The outcome variable was LF case status (positive or negative). Predictors of LF case positivity were assessed using multiple logistic regression models with 95% confidence intervals (CI). Case positivity rate (CPR) for the four years was 15.8% with higher odds of positivity among age group 40-49 years (aOR = 1.40; 95% CI 1.21-1.62), males (aOR = 1.11; 95% CI 1.03-1.20), those with formal education (aOR = 1.33; 95% CI 1.13-1.56), artisans (aOR = 1.70; 95% CI 1.28-2.27), religious leaders (aOR = 1.62; 95% CI 1.04-2.52), farmers (aOR = 1.48; 95% CI 1.21-1.81), and symptomatic individuals (aOR = 2.36; 95% CI 2.09-2.68). Being a health worker (aOR = 0.69; 95% CI 0.53-0.91), a teacher (aOR = 0.69; 95% CI 0.53-0.89) and cases reporting in the 3rd quarter (aOR = 0.79; 95% CI 0.69-0.92) had lower odds. In a sex-disaggregated analysis, female farmers had higher odds of positivity (aOR = 2.43; 95% CI 1.76-3.38; p < 0.001) than male farmers (aOR = 1.52; 95% CI 1.19-1.96; p < 0.01). Fever (aOR = 2.39; 95% CI 2.00-2.84) and gastrointestinal (GI) symptoms (aOR = 2.15; 95% CI 1.94-2.37) had the highest odds among symptoms. Combination of fever and GI symptoms (aOR = 2.15; 95% CI 1.50-3.10), fever and neurological symptoms (aOR = 6.37; 95% CI 1.49-27.16), fever and musculo-skeletal symptoms (aOR = 2.95; 95% CI 1.37-6.33), fever and cardiopulmonary symptoms (aOR = 1.81; 95% CI 1.24-2.64), and cardiopulmonary and general symptoms (aOR = 1.50; 95% CI 1.19-1.89) were also predictive. Cumulative LF CPR appears high with clearly identified predictors. Targeted interventions with heightened index of suspicion for sociodemographic categories predictive of LF in suspected cases are recommended. Ethnographic and further epidemiological studies could aid better understanding of these associations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The implementation of the country-wide comprehensive sexuality education (CSE) curriculum among in-school adolescents remains abysmally low and mHealth-based interventions are promising. We assessed ...the effect of a mHealth-based CSE on the sexual and reproductive health (SRH) knowledge, attitude and behaviour of in-school adolescents in Ilorin, northcentral Nigeria.
Using schools as clusters, 1280 in-school adolescents were randomised into intervention and control groups. Data was collected at baseline (T
), immediately after the intervention (T
) and 3 months afterwards (T
) on SRH knowledge, attitude and practice of risky sexual behaviour (RSB). Data analysis included test of associations using Chi-square, independent t-test and repeated measures ANOVA. Predictors were identified using binary logistic regression.
In the intervention group, there was a statistically significant main effect on mean knowledge score (F = 2117.252, p = < 0.001) and mean attitude score (F = 148.493, p = < 0.001) from T
to T
compared to the control group which showed no statistically significant main effects in knowledge (p = 0.073), attitude (p = 0.142) and RSB (p = 0.142). Though the mean RSB score declined from T
to T
, this effect was not statistically significant (F = 0.558, p = 0.572). Post-intervention, being female was a positive predictor of good SRH knowledge; being male was a positive predictor of RSB while being in a higher-class level was a negative predictor of RSB.
The mHealth-based CSE was effective in improving SRH knowledge and attitude among in-school adolescents. This strategy should be strengthened to bridge the SRH knowledge and attitude gap among in-school adolescents. Trial registration Retrospectively registered on the Pan African Clinical Trial Registry (pactr.samrc.ac.za) on 19 October 2023. Identification number: PACTR202310485136014.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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 (M
PRO
) 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 M
PRO
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 (IC
50
) 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 IC
50
values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (M
PRO
) with IC
50
values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.
Conclusion
The IC
50
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.
The aim of this study was to describe the extent of self-reported non-communicable diseases (NCDs) among highly active antiretroviral therapy (HAART) recipients in Kagera region in Tanzania and their ...effect on health-related quality of life (HRQOL). This study was conducted 2 years after HAART administration was started in Kagera region.
The SF-36 questionnaire was used to collect the HRQOL data of 329 HAART recipients. Questions on the NCDs, socio-demographic characteristics and treatment information were validated and added to the SF-36. Bivariate analyses involving socio-demographic characteristics and SF-36 scores of the recipients were performed. Multiple logistic regression was employed to compute adjusted odds ratios for different explanatory variables on physical functioning and mental health scores.
Respondents who reported having 1 or more NCDs were 57.8% of all the respondents. Arthritis was the commonest NCD (57.8%). Respondents with the NCDs were more likely to have HRQOL scores below the mean of the general Tanzanian population. The population attributable fraction (PAF) for the NCDs on physical functioning was 0.28 and on mental health was 0.22.
Self-reported NCDs were prevalent among the HAART recipients in Kagera region. They accounted for 28% of the physical functioning scores and 22% of the mental health scores that were below the mean of the general Tanzanian population. Therefore, the integration of NCD care is important in the management of HIV/AIDS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cardiovascular diseases (CVDs) are a challenge to populations and health systems worldwide. It is projected that by 2020 about a third of all deaths globally will be caused by CVDs, and that they ...will become the single leading cause of death by 2030. Empirical evidence suggests that there is socioeconomic patterning in the distribution and prevalence of risk factors for CVD, but the exact nature of this relationship in South Africa remains unclear.
To examine the association between socioeconomic status (SES) and risk factors for CVD in a cohort of adult South Africans living in rural and urban communities.
This was a cross-sectional analytical study of baseline data on a population-based cohort of 1 976 SA men and women aged 35 - 70 years who were part of the Cape Town arm of the Prospective Urban and Rural Epidemiology (PURE) Study.
We found a complex association between SES and CVD risk factors, its pattern differing between urban and rural participants. Marital status showed the most consistent association with CVD risk in both groups: widowed participants living in urban communities were more likely to be hypertensive as well as diabetic, while single participants in both locations were more likely to use alcohol and tobacco products. Level of education was the only SES variable that had no significant association with any CVD risk factor in either study group. All measured SES variables were significantly different between urban and rural participants (p<0.05), with diabetes, obesity and alcohol use significantly more prevalent in urban than in rural participants (p<0.05) while hypertension and tobacco use were not (p≥0.05).
In this cohort of South Africans, there were significant associations between SES and CVD risk, with marked differences in these associations between rural and urban locations. These findings highlight the need to consider SES and area of residence when designing interventions for CVD prevention and control.
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.
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 (M
) enzymes.
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 M
activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.
Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC
) 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 IC
values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (M
) with IC
values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.
The IC
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.
Philosophiae Doctor - PhD
Pain is a complex biopsychosocial phenomenon that can have a profound impact on people's lives (Access Economics AE, 2007). lts clinical relevance is well known - pain is ...suggestive of "actual or potential tissue damage" and plays a role in the diagnosis and clinical management of diseases and/or injury (International Association for the Study of Pain IASP, 1986). It has both sensory and emotional aspects and is behaviourally expressed by how it is communicated by the sufferer and by its effect on the sufferer's behaviour (IASP, 1986; Linton, 2005; AE, 2007). Even though the experience of pain is associated with tissue damage or is described in terms of such damage, this association is variable so that "the size of an injury can be a poor guide as to how much an individual experiences pain" (AE, 2007). In fact, pain can exist without an objective evidence of tissue damage making pain the "ultimate subjective experience" (Odendaal, 2006). This phenomenon may relate to the fact that the interpretation of nociceptive signals as pain is influenced by a number of personal and environmental factors including past experience, integrity of the nervous system, beliefs and the situation in which tissue damage occurs (Eccleston, 2001; Turk, 2002a; Flor and Hermann, 2004; AE, 2007). As such, decisive and objective measurements are difficult to arrive at and pain is not always easily assessed by the healthcare provider. The translation of pain from acute to chronic however, means that pain and discomfort remains;
beyond the normal time of healing and by definition, persists either continuously or intermittently for 3 months or longer (Elliot et al., 1999). This changes the physiognomy of pain and the condition of chronic pain ensues. Chronic pain is an important but often neglected public health problem. It is disabling and associated with interference in normal activities of daily living (ADLs) such as work, home chores, family and sporting activities. Research shows that chronic pain is a key complaint that motivates many to seek health care (Crook et al., 1984, 1989; Sullivan et al., 1990; Smith et al., 1996; Mantyselka et al., 2001, 2002; Eriksen et al., 2004; AE, 2007) leading to high and ongoing;
consumption of treatments (AE, 2007). In fact, studies have shown that persons with chronic pain use health services up to five times more frequently than the rest of the population (Von Korff et al., 1990, 1991; Elliot et al., 1999; Eriksen et al., 2004). Side-effects of treatment;
are common with medication use including gastric problems such as ulcerations, nausea, constipation and mental slowing or confusion which can affect functioning. Chronic pam is also associated with mood and sleep disturbances such as depression or adjustment problems and trouble getting to sleep and/or frequent wakening during the night. For the sufferer, the effect of disuse of the aspect of the body in which pain is experienced is another manifestation of chronic pain. Muscles and joints become de-conditioned and pain sufferers may lose general body fitness (AE, 2007). Within the community, pain is a common cause of considerable suffering and disability affecting the general health and quality of life of individuals (Von Korff et al., 1990, 1992; Magni et al., 1990,1993; Walsh et al., 1992; Smith et al., 1996,2001; Verhaak et al., 1998; Elliot et al., 1999, 2002; Blyth et al., 2001; Reyes-Gibby et al., 2002; Lanteri-Minet et al., 2003). Significant amounts of working days are lost among the labour force impacting a profound economic and social toll on society (Bowsher et al., 1991; Elliot et al., 1999; Blyth et al., 2003; Igumbor et al.,2003). Simply put, "chronic pain is a human tragedy" (Odendaal, 2006). It is a serious and common problem that causes distress to patients and their caregivers, is a burden on health care professionals and health care resources and results in significant lost productivity. Chronic pain is therefore a problem of public health importance.
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