Role of vaccines in preventing influenza in healthy children.

The role of an influenza vaccine is to minimise illness and death. Vaccines provide good protection against influenza strains and significantly reduce time off work. However, the recommendation for use depends on the efficacy, effectiveness and safety of the vaccines. We highlight a Cochrane review that sought to determine the efficacy, effectiveness and safety of seasonal influenza vaccines in healthy children, and provide implications for practice for vaccination of children. The findings suggest that influenza vaccines play a key role in reducing serious morbidity and mortality among children. There were few data available to provide firm conclusions on adverse events. Vaccinating against influenza not only reduces its incidence among children, but also extends these benefits to the unvaccinated population, such as the elderly. In light of the many direct and indirect benefits of vaccinating children aged 2 - 16 years, there is a need to provide access to influenza vaccines to all eligible South African children.

Taking stock of global immunisation coverage progress: the gains, the losses and the journey ahead.

Despite the enormous benefits of vaccination, global immunisation coverage progress has stalled and remains suboptimal in many countries. In this commentary, we review the recently published update of the World Health Organization and United Nations Children's Fund Estimates of National Immunization Coverage. We highlight trends in which, despite substantial gains made in improving immunisation coverage at the global level, there remain numerous challenges with reaching and sustaining optimal coverage. We contextualise the trends by exploring plausible supply- and demand-side root causes. Based on these, we stress the need for targeted, context-appropriate strategies for reaching and maintaining optimal immunisation coverage.

Lessons learnt during the national introduction of human papillomavirus (HPV) vaccination programmes in 6 African countries: Stakeholders' perspectives.

BACKGROUND: Infection with human papillomavirus (HPV) significantly increases the risk of developing cervical cancer later in life. Therefore, globally, HPV vaccines targeted to pre-adolescent and adolescent girls have been on the rise since the licensure in 2006. However, the introduction of HPV vaccines has been relatively slow in Africa. At the end of 2016, only 8 of the 54 countries in Africa were reported to have introduced HPV vaccination at a national level. By 2019, the number of countries had grown marginally to 11. OBJECTIVES: To investigate stakeholders' perspectives on the experiences, challenges and lessons learnt during national HPV vaccine introduction in Africa. METHODS: A questionnaire was administered to selected participants from 8 African countries. These countries had successfully introduced HPV vaccination at a national level by the end of 2016. We used in-depth interviews and self-administered online questionnaires for data collection and analysis. Data are presented without naming the country or participants; therefore, readers will not be able to identify the results that are specific to individual countries. Narrative and thematic reporting were used to describe the results. RESULTS: We obtained results from 6 of the 8 targeted countries. The challenges reported during HPV vaccination programmes were: identifying the target population, using a school-based vaccine-delivery strategy, obtaining political support, the need to integrate HPV vaccination with existing school health programmes and engaging multiple stakeholders. These challenges were similar in all 6 countries. The lessons learnt were that a school-based delivery strategy is a successful approach for national HPV vaccination, and that identifying girls for vaccination at schools was less challenging if implemented through a class-based instead of an age-based approach. CONCLUSIONS: Most African countries do not have established platforms to deliver vaccines to pre-adolescent and adolescent populations. The successful introduction of the HPV vaccine through school-based vaccination strategies in African countries may have created a platform to deliver other adolescent vaccines. The similarity of the study findings across the 6 participating countries further strengthens the need to document and disseminate the challenges and lessons learnt during HPV vaccine introduction in Africa. Documentation and dissemination of the challenges and lessons learnt are useful to other countries in Africa that plan to introduce an HPV vaccination programme, and possibly other adolescent vaccines.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19.

Convalescent plasma is being considered as a potential therapy for COVID-19. We highlight and contextualise the findings of a recent Cochrane rapid review that evaluated the effectiveness and safety of convalescent plasma or hyperimmune immunoglobulin transfusion in the treatment of people with COVID-19. The review found low-certainty evidence of the therapeutic effectiveness and safety of convalescent plasma. As the novel coronavirus continues to spread in South Africa (SA), convalescent plasma may offer a therapeutic ray of hope for mitigating the morbidity and mortality burdens of the disease. Further investigation of the clinical benefits of the therapy in well-designed studies is needed to provide more evidence that will guide COVID-19 treatment decision-making in the SA context.

Healthcare workers' adherence to infection prevention and control guidelines for respiratory infectious diseases: A rapid qualitative evidence synthesis.

COVID-19 spreads easily between people who are in close contact, or through coughs and sneezes. As the number of cases continues to increase, healthcare workers (HCWs) are notably at risk as a result of frequency of contact with suspected cases or infected people. Use of infection prevention and control (IPC) strategies by HCWs is therefore important. We summarise the evidence from a rapid Cochrane qualitative evidence synthesis by Houghton et al. on barriers and facilitators to HCWs' adherence to IPC guidelines for respiratory infectious diseases.

Rubella seroprevalence using residual samples from the South African measles surveillance program: a cross-sectional analytic study.

Introduction: South Africa is yet to introduce rubella-containing vaccines (RCV) into its routine immunization schedule. Selecting the target population when introducing RCV should take into account the ages of susceptible individuals in the population. We aimed to determine the seroprevalence of antibodies to rubella and characterize immunity gaps among individuals of all ages in South Africa. Methods: We tested for rubella immunoglobulin G (IgG) antibodies with a commercial enzyme-linked immunosorbent assay. We used residual samples collected from 2016 through 2018 as part of the national measles surveillance program. We only tested samples that were negative for measles and rubella immunoglobulin M (IgM) and explored the association between rubella susceptibility (IgG negative) and predictor variables (year of sample collection, age, sex, and province of residence) using logistic regression analysis. Results: We obtained results for 6057 records. Rubella susceptibility was highest among Individuals aged zero to 11 months (81.9%), followed by children 1 to 5 years old (71.5%), 6 to 10 y old (40.9%) and 11 to 15 y old (31.25) while the smallest proportion of susceptible individuals was among those 16 to 49 y old (19.9%). Females were less likely to be susceptible to rubella compared to males (OR = 0.79 (95%CI: 0.71-0.87), P < .001) in unadjusted analysis but this effect was not observed after adjusting for age and province. In multivariable logistic regression, age (OR = 6.24 (4.52-8.63), P < .001) and province of residence (OR = 0.97 (95%CI: 0.95-0.99), P = .01) were associated with rubella susceptibility. Conclusion: In the absence of rubella vaccination in the Expanded Program on Immunization in South Africa, the bulk of individuals susceptible to rubella are children under 16 y old. About 20% of individuals 16 to 49 y old are susceptible to rubella. This susceptibility gap must be born in mind during RCV introduction.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID­19

Convalescent plasma is being considered as a potential therapy for COVID­19. We highlight and contextualise the findings of a recent Cochrane rapid review that evaluated the effectiveness and safety of convalescent plasma or hyperimmune immunoglobulin transfusion in the treatment of people with COVID­19. The review found low­certainty evidence of the therapeutic effectiveness and safety of convalescent plasma. As the novel coronavirus continues to spread in South Africa (SA), convalescent plasma may offer a therapeutic ray of hope for mitigating the morbidity and mortality burdens of the disease. Further investigation of the clinical benefits of the therapy in well-designed studies is needed to provide more evidence that will guide COVID-19 treatment decision-making in the SA context

Healthcare workers' adherence to infection prevention and control guidelines for respiratory infectious diseases: A rapid qualitative evidence synthesis

COVID-19 spreads easily between people who are in close contact, or through coughs and sneezes. As the number of cases continues to increase, healthcare workers (HCWs) are notably at risk as a result of frequency of contact with suspected cases or infected people. Use of infection prevention and control (IPC) strategies by HCWs is therefore important. We summarise the evidence from a rapid Cochrane qualitative evidence synthesis by Houghton et al. on barriers and facilitators to HCWs' adherence to IPC guidelines for respiratory infectious diseases

Communication regarding routine childhood vaccination.

Vaccine hesitancy is an emerging problem in South Africa (SA), which threatens to erode the country's immunisation achievements. Communication interventions may be an effective strategy for addressing vaccine hesitancy. We highlight a Cochrane review of qualitative evidence that explored parents' views and experiences of communication regarding childhood vaccinations, and provide implications for practice that are relevant to the SA context. The findings suggest that healthcare providers (HCPs) play a central role in childhood vaccination attitudes and decision-making. Therefore, capacitating HCPs to promote vaccination with confidence is key to effective communication to address vaccine hesitancy in SA.

Neonatal, infant and child health in South Africa: Reflecting on the past towards a better future.

Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.

Human papillomavirus vaccination acceptance and hesitancy in South Africa: Research and policy agenda.

Cervical cancer is responsible for one-quarter of a million deaths per year worldwide. In South Africa (SA), cervical cancer is the leading cause of cancer deaths among women aged 15 - 44 years. Human papillomavirus (HPV) vaccines provide a safe and highly effective means to reduce the burden of cervical cancer. The World Health Organization initiated a plan for the elimination of cervical cancer; the programme's success relies on the introduction and high uptake of HPV vaccines globally. SA introduced a school-based HPV vaccination programme in 2014, but uptake is not as high as expected. Suboptimal HPV vaccination coverage may result from various factors, including vaccine hesitancy. Vaccine-hesitant parents may delay or refuse HPV vaccination for their daughters. Tailored interventions are needed to address this. However, knowledge regarding vaccine hesitancy and policies to address this hesitancy in SA are currently limited. While SA has taken commendable steps in cervical cancer prevention by implementing and financing the HPV vaccination programme, it is imperative that there are clear policies in place to help strengthen the programme. These policies need to clarify areas of uncertainty that may lead to mistrust, and pre-empt factors that will cause hesitancy. Equally important is that local research should be conducted to better understand HPV vaccination hesitancy and other determinants of uptake to further inform and shape national policies.

Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis.

Sputum induction (SI) has been proposed as the optimal sample collection method for patients with paucibacillary tuberculosis (TB). Studies reporting the culture of Mycobacterium tuberculosis from SI were reviewed. A random-effects meta-analysis of diagnostic yield (numerator M. tuberculosis SI culture-positive cases; denominator all culture-positive cases) was conducted. Diagnostic yields (95% confidence intervals, CIs) were displayed as Forest plots. Heterogeneity was evaluated using Chi-squared and I-squared tests and meta-regression analysis. Ninety publications were screened, 28 full-text papers reviewed, and 17 analyzed. Collectively, n=627 SI culture-positive cases among n=975 culture-confirmed TB cases were reported. The diagnostic yield of SI ranged from 35 to 95%. The pooled diagnostic yield was 74% (CI 65-81%), with significant heterogeneity (p<0.0001, I2=86%). There were no statistically significant differences in the yield between sub-groups defined by human immunodeficiency virus (HIV) prevalence or age. Univariate analysis demonstrated that the use of fiberoptic bronchoscopy (FOB) as the comparator method was associated with a 22% reduction (CI 2-42%) in the diagnostic yield of SI. However, after adjustment for confounding, the meta-regression analysis showed that FOB usage (p=0.21) and saline concentration (p=0.31) were not independently associated with the diagnostic yield. SI will detect approximately three-quarters of M. tuberculosis culture-positive cases under study conditions. Significant heterogeneity in the diagnostic yield was not explained by HIV prevalence, age, or the use of FOB as the comparator method. The use of a particular nebulized saline concentration for SI cannot be recommended on the basis of this meta-regression analysis.

A systematic review of randomized controlled trials to reduce hemorrhage during myomectomy for uterine fibroids.

OBJECTIVE: To assess the effectiveness and safety of interventions to reduce blood loss during myomectomy. METHODS: Electronic searches of the Cochrane Library, MEDLINE, and EMBASE, between 1966 and 2006 for randomized controlled trials (RCTs). RESULTS: We found significant reductions in blood loss with vaginal misoprostol (weighted mean difference [WMD] -149.00 mL, 95% confidence interval [CI] -229.24 to -68.76); intramyometrial vasopressin and analogues (WMD -298.72 mL, 95% CI -593.10 to -4.34); intramyometrial bupivacaine plus epinephrine (WMD -68.60 mL, 95% CI -93.69 to -43.51); and pericervical tourniquet (WMD -1870.00 mL, 95% CI -2547.16 to -1192.84). There was no evidence of effect in blood loss with myoma enucleation by morcellation and oxytocin. CONCLUSION: There is limited evidence from a few RCTs that some interventions may reduce bleeding during myomectomy. There is need for adequately powered RCTs to shed more light on the effectiveness, safety, and cost of different interventions to reduce blood loss during myomectomy.

Mortality in Patients Treated for Tuberculous Pericarditis in Sub-Saharan Africa

Objective: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. Design: Between 1 March 2004 and 31 October 2004; we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon; Nigeria; and South Africa; and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study; with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression; we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. Results: We obtained the vital status of 174 (94) patients (median age 33; range 14-87 years). The overall mortality rate was 26. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40versus 17; P=0.001). Independent predictors of death during follow-up were: (1) a proven non-tuberculosis final diagnosis (hazard ratio [HR] 5.35; 95confidence interval 1.76 to 16.25); (2) the presence of clinical signs of HIV infection (HR 2.28; 1.14-4.56); (3) co-existent pulmonary tuberculosis (HR 2.33; 1.20-4.54); and (4) older age (HR 1.02; 1.01-1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80; 0.90-3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34; 0.10-1.19). Conclusion : A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africans. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease

Beta-blockers for hypertension.

BACKGROUND: Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. OBJECTIVES: To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. SEARCH STRATEGY: We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. SELECTION CRITERIA: We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. DATA COLLECTION AND ANALYSIS: At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance. MAIN RESULTS: Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs. AUTHORS' CONCLUSIONS: The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

Interventions to reduce haemorrhage during myomectomy for fibroids.

BACKGROUND: Uterine myomas (fibroids) are benign tumours of the uterus. Myomectomy, the surgical removal of the myomas, is an important treatment option especially for women who desire to preserve their uteri. The major problem with myomectomy is excessive bleeding from increased uterine blood supply, and this can be life-threatening and prolong postoperative stay. Knowledge of the effectiveness of the interventions used to reduce blood loss during myomectomy is essential to enable evidence-based clinical decisions. OBJECTIVES: To assess the effectiveness and safety of interventions (other than GnRH analogues) to reduce blood loss during myomectomy. SEARCH STRATEGY: Electronic searches were undertaken in the Cochrane Menstrual Disorders and Subfertility Group specialised register, CENTRAL (Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006), EMBASE (1980 to March 2006), Current Contents (1993 to March 2006), the National Research Register, and the National Library of Medicine's Clinical Trial Register (up to March 2006). SELECTION CRITERIA: Only randomised controlled trials (RCTs) that compared interventions to reduce blood loss during myomectomy to placebo or no treatment were included. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the methodological quality and extracted data. We expressed study results as weighted mean differences (WMD) for continuous data, and odds ratios for dichotomous data. MAIN RESULTS: Eight RCTs met the inclusion criteria: two on intramyometrial vasopressin and analogues, and one each on vaginal misoprostol, IV oxytocin, pericervical tourniquet, chemical dissection with mesna, intramyometrial bupivacaine plus epinephrine and the enucleation of myoma by morcellation while it is attached to the uterus. We found significant reductions in blood loss with misoprostol (WMD -149.00 ml, 95% confidence interval [CI] -229.24 to -68.76), vasopressin and analogues (WMD -298.72 ml, 95% CI -593.10 to -4.34), bupivacaine plus epinephrine (WMD -68.60 ml, 95% CI -93.69 to - 43.51), and pericervical tourniquet (WMD -1870.00 ml, 95% CI -2547.16 to -1192.84). There was no evidence of effect in blood loss with myoma enucleation by morcellation and oxytocin. The trials did not assess the tolerability and costs of different interventions. AUTHORS' CONCLUSIONS: There is limited evidence from a few RCTs that misoprostol, vasopressin, bupivacaine plus epinephrine, tourniquet and mesna may reduce bleeding during myomectomy. There is no evidence that oxytocin and morcellation have an effect on intraoperative blood loss. There is need for adequately powered RCTs to shed more light on the effectiveness, safety and costs of different interventions in reducing blood loss during myomectomy.

The epidemiology of stroke in sickle cell patients in Yaounde, Cameroon.

BACKGROUND AND PURPOSE: Stroke, a severe and recurrent but preventable complication of sickle cell disease (SCD), has not been well studied in Cameroon. To obtain baseline data towards the development of a national stroke prevention programme in SCD, we studied a sample of sickle cell patients with the aim of determining stroke prevalence, clinical presentation and management practices. PATIENTS AND METHODS: Homozygous sickle cell patients in two centres in Yaounde were screened for stroke, in a cross-sectional study. Stroke was diagnosed clinically and confirmed where possible with brain computerized tomography. The National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale (mRS) were used to assess stroke severity. Management practices were noted from patient charts. RESULTS: One hundred and twenty patients aged 7 months to 35 years (mean age 13.49+/-8.79 years) were included. Eight cases of stroke (mean age 16.6+/-11.2 years) were identified, giving a stroke prevalence of 6.67%. Cerebral infarction was thrice as common as cerebral hemorrhage and clinical presentation was classical. Cerebral infarction was more frequent in patients aged below 20 years and hemorrhage in those above 20 (p=0.11). The annual recurrence rate was 25%. Missed diagnosis rate by attending physician was 25%. The NIHSS and mRS showed high stroke severity. Stroke management practices were insufficient and no patient received any form of stroke prophylaxis. CONCLUSION: Stroke prevalence and presentation in sickle cell patients in Yaounde is similar to that observed in developed countries, but the wide management gap calls for rapid action. Our situation is ideal for the study of the natural history of stroke in sickle cell disease.