Pneumococcal conjugate vaccine – a health priority

Pneumonia is a major cause of childhood mortality and morbidity. Streptococcus pneumoniae is the most important bacterial pathogen causing pneumonia in children. The HIV epidemic has increased the burden and severity of childhood pneumococcal pneumonia and invasive disease fortyfold. Pneumococcal conjugate vaccine (PCV) is a highly effective intervention to reduce invasive pneumococcal disease and pneumonia. Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccineserotype- specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in antimicrobial-resistant invasive disease. PCV may also reduce childhood mortality, especially in places with limited access to health care, as shown in Gambian study in which PCV reduced childhood mortality by 16%. In addition to the direct effects of PCV, there is a substantial reduction in disease burden through indirect protection of non-vaccinated populations. PCV is immunogenic in HIV-infected children and provides protection against invasive disease or pneumonia in a substantial number of children. Although the efficacy of PCV for prevention of invasive disease or pneumonia is lower in HIV-infected compared to -uninfected children, the overall burden of disease prevented is much greater in HIV-infected children because of the higher burden of pneumococcal disease in these children. Consequently, vaccine-preventable invasive disease is almost 60 times higher in HIV-infected compared to -uninfected children, while the reduction in pneumonia in HIV-infected children is 15 times greater. However, the long-term efficacy of PCV wanes in HIVinfected children who are not taking antiretroviral therapy, and booster doses are probably indicated. Although there is concern about the potential for replacement disease due to non-vaccine serotypes, a substantial and sustained reduction in invasive disease has occurred overall in populations with widespread childhood immunisation. Routine childhood immunisation is now the standard of care in most developed countries. However, PCV is much less accessible to children in developing countries due to cost and availability. Cost-effectiveness analysis indicates that use of PCV is potentially highly cost-effective, at tiered pricing, even in very low-income countries. Widespread availability and vaccination with PCV is urgently needed for all children under 2 years of age in South Africa. In addition, the use of PCV for all HIV-infected children under 9 years should be prioritised.South African Medical Journal Vol. 98 (6) 2008 pp. 463-46

Планування індивідуальних тренувальних навантажень у швидкісно-силових видах легкої атлетики

Використання контролю за функціональним станом центральної нервової системи і нервово-м'язового апарату позитивно впливає під час планування індивідуальних тренувальних навантажень спортсменів, які спеціалізуються у швидкісно-силових видах легкої атлетики. Набули подальшого розвитку дані про нормування параметрів (потужності м'язів, вибухової м'язової сили, час включення м'язів, ступінь активації, втоми центральної нервової системи), які характеризують функціональний стан організму спортсменів. Доповнено дані та розширено уявлення провідної ролі контролю у процесі індивідуальної адаптації організму спортсменів до тренувальних навантажень. Практична значимість полягає у тому, що результати дослідження можуть бути запроваджено під час планування навчально-тренувального процесу спортсменів, які спеціалізуються у швидкісно-силових видах легкої атлетики, юними спортсменами дитячо-юнацьких спортивних шкіл, збірними командами різного рангу, на всіх рівнях майстерності. Це дозволяє тренерам планувати оптимальні параметри індивідуальних тренувальних навантажень та використовувати дидактичний принцип доступності та індивідуалізації у тренувальному процесі річного циклу підготовки.Использование контроля за функциональным состоянием центральной нервной системы и нервно-мышечного аппарата оказывает положительное влияние при планировании индивидуальных тренировочных нагрузок спортсменов, специализирующихся в скоростно-силовых видах легкой атлетики. Получили дальнейшее развитие данные о нормировании параметров (мощности мышц, взрывной мышечной силы, времени включения мышц, степени активации, усталости центральной нервной системы), которые характеризуют функциональное состояние организма спортсменов. Дополнены данные и расширены представления ведущей роли контроля в процессе индивидуальной адаптации организма спортсменов к тренировочным нагрузкам. Практическая значимость состоит в том, что результаты исследования могут быть введены при планировании учебно-тренировочного процесса спортсменов, специализирующихся в скоростно-силовых видах легкой атлетики, юными спортсменами детско-юношеских спортивных школ, сборными командами разного ранга, на всех уровнях мастерства. Это позволяет тренерам планировать оптимальные параметры индивидуальных тренировочных нагрузок и использовать дидактический принцип доступности и индивидуализации в учебном процессе годового цикла подготовки.The use of control over the functional state of the central nervous system and neuromuscular apparatus has a positive effect when planning individual training loads of athletes who specialize in speed and strength athletics. Data on the normalization of parameters (muscle power, explosive muscle strength, time of muscle activation, degree of activation, fatigue of the central nervous system), which characterize the functional state of the body of athletes, have been further developed. The data are supplemented and the idea of the leading role of control in the process of individual adaptation of the body of athletes to training loads is expanded. The practical significance is that the results of the study can be introduced during the planning of the training process of athletes who specialize in speed and strength athletics, young athletes of children's and youth sports schools, national teams of various ranks, at all skill levels. This allows trainers to plan the optimal parameters of individual training loads and use the didactic principle of accessibility and individualization in the training process of the annual training cycle

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

Towards a population-based threshold of protection for COVID-19 vaccines

Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42–559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35–102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious

High incidence of antimicrobial resistant organisms including extended spectrum beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus in nasopharyngeal and blood isolates of HIV-infected children from Cape Town, South Africa

<p>Abstract</p> <p>Background</p> <p>There is little information on nasopharyngeal (NP) flora or bacteremia in HIV-infected children. Our aim was to describe the organisms and antimicrobial resistance patterns in children enrolled in a prospective study comparing daily and three times weekly trimethoprim-sulfamethoxazole (TMP-SMX) and isoniazid (INH) or placebo prophylaxis.</p> <p>Methods</p> <p>NP swabs were taken at baseline from HIV-infected children enrolled in the study. Standard microbiological techniques were used. Children were grouped according to previous or current exposure to TMP-SMX and whether enrolled to the study during a period of hospitalization. Blood culture results were also recorded within 12 months of baseline.</p> <p>Results</p> <p>Two hundred and three children, median age 1.8 (Interquartile [IQ]: 0.7–4) years had NP swabs submitted for culture. One hundred and eighty-four (90.7%) had either stage B or C HIV disease. One hundred and forty-one (69.8%) were receiving TMP-SMX and 19 (9.4%) were on antiretroviral therapy. The majority, 168 (82%) had a history of hospitalization and 91 (44.8%) were enrolled during a period of hospitalization. Thirty-two subjects (16.2%) died within 12 months of study entry.</p> <p>One hundred and eighty-one potential pathogens were found in 167 children. The most commonly isolated organisms were <it>Streptococcus pneumoniae </it>(48: 22.2%), Gram-negative respiratory organisms (<it>Haemophilus influenzae </it>and <it>Moraxella catarrhalis</it>) (47: 21.8%), <it>Staphylococcus aureus </it>(44: 20.4%), Enterobacteriaceae 32 (14.8%) and Pseudomonas 5 (2.3%).</p> <p>Resistance to TMP-SMX occurred in > 80% of pathogens except for <it>M. catarrhalis </it>(2: 18.2% of tested organisms). TMP-SMX resistance tended to be higher in those receiving it at baseline (p = 0.065). Carriage of Methicillin resistant <it>S. aureus </it>(MRSA) was significantly associated with being on TMP-SMX at baseline (p = 0.002). Minimal inhibitory concentrations (MIC) to penicillin were determined for 18 <it>S. pneumoniae </it>isolates: 7 (38.9%) were fully sensitive (MIC ≤ 0.06 μg/ml), 9 (50%) had intermediate resistance (MIC 0.12 – 1 μg/ml) and 2 (11.1%) had high level resistance (MIC ≥2 μg/ml). Fifty percent of Enterobacteriaceae produced extended spectrum beta-lactamases (ESBL) (resistant to third generation cephalosporins) and 56% were resistant to gentamicin. Seventy-seven percent of <it>S. aureus </it>were MRSA. Carriage of resistant organisms was not associated with hospitalization.</p> <p>On multivariate logistic regression, risk factors for colonization with Enterobacteriaceae were age ≤ one year (Odds ratio 4.4; 95% Confidence Interval 1.9–10.9; p = 0.0008) and CDC stage C disease (Odds ratio 3.6; 95% Confidence Interval 1.5–8.6; p = 0.005)</p> <p>Nineteen (9.4%) subjects had 23 episodes of bacteremia. Enterobacteriaceae were most commonly isolated (13 of 25 isolates), of which 6 (46%) produced ESBL and were resistant to gentamicin.</p> <p>Conclusion</p> <p>HIV-infected children are colonized with potential pathogens, most of which are resistant to commonly used antibiotics. TMP-SMX resistance is extremely common. Antibiotic resistance is widespread in colonizing organisms and those causing invasive disease. Antibiotic recommendations should take cognizance of resistance patterns. Antibiotics appropriate for ESBL-producing Enterobacteriaceae and MRSA should be used for severely ill HIV-infected children in our region. Further study of antibiotic resistance patterns in HIV-infected children from other areas is needed.</p

Identification of Colletotrichum species associated with anthracnose disease of coffee in Vietnam

Colletotrichum gloeosporioides, C. acutatum, C. capsici and C. boninense associated with anthracnose disease on coffee (Coffea spp.) in Vietnam were identified based on morphology and DNA analysis. Phylogenetic analysis of DNA sequences from the internal transcribed spacer region of nuclear rDNA and a portion of mitochondrial small subunit rRNA were concordant and allowed good separation of the taxa. We found several Colletotrichum isolates of unknown species and their taxonomic position remains unresolved. The majority of Vietnamese isolates belonged to C. gloeosporioides and they grouped together with the coffee berry disease (CBD) fungus, C. kahawae. However, C. kahawae could be distinguished from the Vietnamese C. gloeosporioides isolates based on ammonium tartrate utilization, growth rate and pathogenictity. C. gloeosporioides isolates were more pathogenic on detached green berries than isolates of the other species, i.e. C. acutatum, C capsici and C. boninense. Some of the C. gloeosporioides isolates produced slightly sunken lesion on green berries resembling CBD symptoms but it did not destroy the bean. We did not find any evidence of the presence of C. kahawae in Vietnam