Along with the legends about epidemic demons, China has developed over the centuries a medical approach to epidemic diseases based on the teachings of
Huang Di Nei Jing
(《黄帝内经》
Huangdi's Internal ...Classic
),
Nan Jing
(《难经》
Classic of Difficult Issues
), and
Shang Han Lun
(《伤寒论》
Treatise on Cold Damage
). Other doctors and scientists participated in this evolution of knowledge, like Wang Shuhe (王叔和), Ge Hong (葛洪), Chao Yuanfang (巢元方), Sun Simiao (孙思邈), and Liu Wansu (刘完素). However, it was in the 17
th
century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit, Wu Youke (吴又可 1582–1652) first foresaw the existence of microorganisms as we know them now. His
Wen Yi Lun
(《瘟疫论》
Treatise on Pestilence
) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21
st
century. After them, traditional Chinese medicine developed a comprehensive method of diagnosing and treating of these diseases (Epidemic Diseases Theory 瘟疫学说) within the School of Heat Diseases (温病学派). In a third article, we will examine some applications in the treatment of the SARS 2003–2004 epidemic (非典型肺炎) and the current COVID-19 (新型冠状病毒肺炎) pandemic.
Background To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals). Methods In a ...double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later. Results RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval CI, 32.9%–67.1%) and 32% (95% CI, 17.6%–47.6%), respectively. At the time of initial challenge, the RTS,S/AS01B group had greater circumsporozoite protein (CSP)-specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP-specific CD4+ T cells expressing ⩾2 activation markers (interleukin-2, interferon IFN-γ, tumor necrosis factor-α, or CD40L), and more ex vivo IFN-γ enzyme-linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP-specific IgG titer (geometric mean titer, 188 vs 73 µg/mL; P <.001), higher numbers of CSP-specific CD4+ T cells per 106 CD4+ T cells (median, 963 vs 308 CSP-specific CD4+ T cells/106 CD4+ T cells; P <.001), and higher numbers of ex vivo IFN-γ ELISPOTs (mean, 212 vs 96 spots/million cells; P <.001 ). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected. Conclusions The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to deter-mine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection. Trial registration ClinicalTrials.gov identifier NCT00075049.
Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of ...Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children.
In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain.
The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval CI, 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine.
On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.).
Epidemic diseases, known and studied in China since antiquity, are one of the main chapters of the School of Exogenous Febrile Diseases (温病学派). Along with the legends about epidemic demons, China has ...developed over the centuries a medical approach based on the teachings of Huang Di Nei Jing (《黄帝内经》Internal Classic), Nan Jing (《难经》Classic of Difficulties), and Shang Han Lun (《伤寒论》Treatise of Harmful Cold). However, it was in the 17th century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit Wu Youxing (吴有性) first foresaw the existence of microorganisms as we know them now. His Wen Yi Lun (《瘟疫论》Treatise on Pestilences) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21st century: severe acute respiratory syndrome 2003–2004 and the COVID-19 pandemic are perfect examples. In this first article, which will be followed by two others, we will examine the classical and modern Chinese definitions of these dreadful plagues.
Summary Background RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5–17 month old children, during an average of 8 months ...follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up. Methods Between March, 2007, and October, 2008, we enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe, Tanzania. Computer-generated block randomisation was used to randomly assign participants (1:1) to receive three doses (at month 0, 1, and 2) of either RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time to first clinical malaria episode, defined as the presence of fever (temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL or more. Follow-up was 12 months for children from Korogwe and 15 months for children from Kilifi. Primary analysis was per protocol. In a post-hoc modelling analysis we characterised the associations between anti-circumsporozoite antibodies and protection against clinical malaria episodes. This study is registered with ClinicalTrials.gov , number NCT00380393. Findings 894 children were assigned, 447 in each treatment group. In the per-protocol analysis, 82 of 415 children in the RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI 19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12 months after the third dose, anti-circumsporozoite antibody titre data were available for 390 children in the RTS,S/AS01E group and 391 in the rabies group. A mean of 15 months (range 12–18 months) data were available for 172 children in the RTS,S/AS01E group and 155 in the rabies group. These titres at 1 month after the third dose were not associated with protection, but titres at 6·5 months were. The level of protection increased abruptly over a narrow range of antibody concentrations. The most common adverse events were pneumonia, febrile convulsion, gastroenteritis, and P falciparum malaria. Interpretation RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries. Funding PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline.
► Electricity saving potential for lighting in offices is examined based on literature. ► Feasible reduction of 50% in average electricity use for lighting is identified. ► Electric lighting ...reduction strategies are discussed including daylight harvesting.
This article presents key energy use figures and explores the energy saving potential for electric lighting in office buildings based on a review of relevant literature, with special emphasis on a North European context. The review reveals that theoretical calculations, measurements in full-scale rooms and simulations with validated lighting programs indicate that an energy intensity of around 10kWh/m2yr is a realistic target for office electric lighting in future low energy office buildings. This target would yield a significant reduction in energy intensity of at least 50% compared to the actual average electricity use for lighting (21kWh/m2yr in Sweden). Strategies for reducing energy use for electric lighting are presented and discussed, which include: improvements in lamp, ballast and luminaire technology, use of task/ambient lighting, improvement in maintenance and utilization factor, reduction of maintained illuminance levels and total switch-on time, use of manual dimming and switch-off occupancy sensors. Strategies based on daylight harvesting are also presented and the relevant design aspects such as effects of window characteristics, properties of shading devices, reflectance of inner surfaces, ceiling and partition height are discussed.
The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in ...AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette-Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-γ, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.
Summary Background Malaria remains a leading global health problem that requires the improved use of existing interventions and the accelerated development of new control methods. We aimed to assess ...the safety, immunogenicity, and initial efficacy of the malaria vaccine RTS,S/AS02D in infants in Africa. Methods We did a phase I/IIb double-blind randomised trial of 214 infants in Mozambique. Infants were randomly assigned to receive three doses either of RTS,S/AS02D or the hepatitis B vaccine Engerix-B at ages 10 weeks, 14 weeks, and 18 weeks of age, as well as routine immunisation vaccines given at 8, 12, and 16 weeks of age. The primary endpoint was safety of the RTS,S/AS02D during the first 6 months of the study, and analysis was by intention to treat. Secondary endpoints included immunogenicity and analysis of new Plasmodium falciparum infections during a 3-month follow up after the third dose. Time to new infections in the per-protocol cohort were compared between groups using Cox regression models. This study is registered with ClinicalTrials.gov , number NCT00197028. Findings There were 17 children (15.9%; 95% CI 9.5–24.2) with serious adverse events in each group. In the follow-up which ended on March 6, 2007, there were 31 serious adverse events in the RTS,S/AS02D group and 30 serious adverse events in the Engerix-B group, none of which were reported as related to vaccination. There were four deaths during this same follow-up period; all of them after the active detection of infection period had finished at study month 6 (two in RTSS/AS02D group and two in the Engerix-B group). RTS,S/AS02D induced high titres of anti-circumsporozoite antibodies. 68 first or only P falciparum infections were documented: 22 in the RTS,S/AS02D group and 46 in the control group. The adjusted vaccine efficacy was 65.9% (95% CI 42.6–79.8%, p<0.0001). Interpretation The RTS,S/AS02D malaria vaccine was safe, well tolerated, and immunogenic in young infants. These findings set the stage for expanded phase III efficacy studies to confirm vaccine efficacy against clinical malaria disease.
This research investigates the daylight regulation compliance of existing multi-family housing developments located primarily in Stockholm (Lat.: 59,33 °N), Sweden. A representative sample of 54 ...buildings consisting of 10.888 individual rooms was modelled according to archived documentation drawings and evaluated by use of Radiance simulations, to test their compliance with the current Swedish daylight regulation. The studied buildings were selected according to their relevance to major architectural typologies of Swedish urban planning history (1926–1991). The assessment was based on a point Daylight Factor scheme (DFP), which stipulates that a specific point in a room should achieve a Daylight Factor DFP ≥ 1%, for the room to be sufficiently daylit. Results indicate that specific architectural typologies consistently yield poor DFP levels compared to other ones. A moderate correlation was found between the density of surroundings and the percentage of compliant rooms per housing development. Finally, the results indicate the existence of distinct periods during Swedish urban planning history, when daylight performance of multi-family houses was affected by different planning practices. Future investigations are under development to evaluate the occupants’ perception of daylight in their apartments, to help define new daylight performance indicators and benchmarks for Swedish households, taking into consideration the limitations of the daylight indicator embedded in the current regulation.
•Daylight compliance according to Swedish regulations was tested for 54 buildings.•Three out of four buildings did not comply with the current requirement.•Tower-block and semi-open building typologies exhibited the highest compliance.•Urban density correlated moderately (R2 = 0,645) with development compliance.•Median Daylight Factor correlated strongly (r = 0,979) with regulation metric DFp.
Background We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profile, was immunogenic, and demonstrated efficacy against Plasmodium falciparum malaria disease for 21 ...months. Methods We conducted a randomized, controlled, phase 2b trial of RTS,S/AS02A in 2022 Mozambican children aged 1–4 years. We now report safety results for all randomized subjects and vaccine efficacy (VE) findings for children in the Manhiça area over the 45-month surveillance period. Results During the surveillance period, the VE(2.5–45) (VE over months 2.5–45 of surveillance) against a first or only episode of clinical malaria disease was 30.5% (95% confidence interval CI, 18.9%–40.4%; P <.001 ), and the VE(2.5–45) against all episodes was 25.6% (95% CI, 11.9%–37.1%; P <.001). When the same period was considered, the VE(2.5–45) for subjects protected against severe malaria was 38.3% (95% CI, 3.4%–61.3%; P = .045). At study month 45, the prevalence of P. falciparum was 34% lower in the RTS,S/AS02A group than in the control group (66 12.2% of 541 patients vs 101 18.5% of 547 patients) (P = .004). Conclusion These results show evidence that RTS,S/AS02A maintained protection during the 45-month surveillance period, and they highlight the feasibility of developing an effective vaccine against malaria. In combination with other malaria-control measures, such a vaccine could greatly contribute to reducing the intolerable global burden of this disease. Trial registration ClinicalTrials.gov identifiers NCT00197041 and NCT00323622.
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