Invasive pneumococcal disease is an important cause of severe illness. In South Africa, a national program to vaccinate children with the conjugated pneumococcal vaccine resulted in a substantial ...decline in invasive pneumococcal disease countrywide, including in adults.
The majority of deaths associated with childhood pneumococcal disease occur in Africa.
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In randomized trials conducted in Africa,
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a pneumococcal conjugate vaccine (PCV) was given to infants when they were 6, 10, and 14 weeks of age, without a booster dose. The vaccine showed efficacy for the prevention of invasive pneumococcal disease caused by the nine serotypes contained in the vaccine among infants who were not infected with the human immunodeficiency virus (HIV) (83% efficacy; 95% confidence interval CI, 39 to 97) and among infants who were infected with HIV (65% efficacy; 95% CI, 24 to 86).
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The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and ...meningitis in South Africa, 2012-2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with ...emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents.
Areas covered: Given that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide.
Expert commentary: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention.
Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial ...susceptibility for culture-confirmed neonatal bloodstream infections and meningitis in South Africa.
We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014–19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria.
Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0–6·1). The incidence risk of late-onset sepsis (days 3–27 of life) was 4·9 per 1000 livebirths (4·9–5·0) and that of early-onset sepsis (days 0–2 of life) was 1·1 per 1000 livebirths (1·1–1·1); risk ratio 4·4 (95% CI 4·3–4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period.
We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured.
Bill & Melinda Gates Foundation.
Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination ...decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence ...of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018-2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host-pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.
Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, ...following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere.
We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005-2008) and post-PCV introduction (2012-2013) in children aged 0-59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals.
In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval CI 83,000-140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000-50,000) severe pneumococcal disease cases were estimated in 2012-2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000-6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000-2500) in 2012-2013, a mortality rate difference of 61 per 100,000 child-years.
While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0-59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics ...(ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women.
Methods
From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression.
Results
We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7
p
< 0.001). Women aged 25—29 and > 35 years were less likely to be vaccinated than women aged 18—24 years (OR = 0.9
p
= 0.053; OR = 0.9
p <
0.001). HIV positive status was not associated with vaccination (OR = 1.0
p
= 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489).
Conclusion
Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.
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Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the ...potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We compared the epidemiology of laboratory-confirmed paediatric cryptococcal disease with adult-onset disease in the South African population.
The study was an active, prospective, population-based, ...laboratory-based surveillance in South Africa. We compared cases of paediatric cryptococcosis (<15 years) with cases of adult-onset cryptococcosis that were reported to the surveillance programme between 1 January 2005 and 31 December 2007. The case definition was based on a positive India ink test, cryptococcal antigen test or cryptococcal culture. Clinical case data were obtained at enhanced surveillance sites.
Of 16,192 incident episodes of cryptococcosis in South Africa, 361 (2%) episodes occurred among children. In 2007, incidence was one and 19 cases per 100,000 persons in the general paediatric and adult populations and was 47 and 120 cases per 100,000 persons for HIV-infected children and adults, respectively. Among children, a bimodal peak in incidence was evident in the less than 1-year age group and in the 5 age group. Most children (64%) and adults (63%) were severely immunocompromised (CD4 T-lymphocyte cell count < 50 cells/μl) at the time of diagnosis. On multivariable analysis, children were significantly more likely than adults to be male, diagnosed on blood culture, infected with Cryptococcus gattii, treated with amphotericin B and admitted for a longer stay in hospital.
This series of 361 cases of paediatric cryptococcosis is by far the largest described to date. The diagnosis of cryptococcosis should be considered in the paediatric HIV-infected population, especially among those who are severely immunocompromised.
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