Marilla G. Lucero

The results of routine influenza surveillance in 13 regions in the Philippines from 2006 to 2012 are presented, describing the annual seasonal epidemics of confirmed influenza virus infection, seasonal and alert thresholds, epidemic curve, and circulating influenza strains. Retrospective analysis of Philippine influenza surveillance data from 2006 to 2012 was conducted to determine seasonality with the use of weekly influenza positivity rates and calculating epidemic curves and seasonal and alert thresholds using the World Health Organization (WHO) global epidemiological surveillance standards for influenza. Increased weekly influenza positive rates were observed from June to November, coinciding with the rainy season and school opening. Two or more peaks of influenza activity were observed with different dominant influenza types associated with each peak. A-H1N1, A-H3N2, and two types of B viruses circulated during the influenza season in varying proportions every year. Increased influenza activity for 2012 occurred 8 weeks late in week 29, rather than the expected week of rise of cases in week 21 as depicted in the established average epidemic curve and seasonal threshold. The intensity was severe going above the alert threshold but of short duration. Southern Hemisphere vaccine strains matched circulating influenza virus for more surveillance years than Northern Hemisphere vaccine strains. Influenza seasonality in the Philippines is from June to November. The ideal time to administer Southern Hemisphere influenza vaccine should be from April to May. With two lineages of influenza B circulating annually, quadrivalent vaccine might have more impact on influenza control than trivalent vaccine. Establishment of thresholds and average epidemic curve provide a tool for policy-makers to assess the intensity or severity of the current influenza epidemic even early in its course, to help plan more precisely resources necessary to control the outbreak. Influenza surveillance activities should be continued in the Philippines and funding for such activities should already be incorporated into the Philippine health budget.

Background: A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results: We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions: There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration: Current Controlled Trials ISRCTN62323832

Background: The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns. Method: A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area. Results: We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way. Conclusions: The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural. Trial registration number: ISRCTN: ISRCTN62323832

Pneumonia, caused by Streptococcus pneumoniae, is a major cause of morbidity and mortality among children in low‐income countries. The effectiveness of pneumococcal conjugate vaccines (PCVs) against invasive pneumococcal disease (IPD), pneumonia, and mortality needs to be evaluated. To update the 2004 review on the efficacy of PCVs in preventing vaccine‐serotypes IPD (VT‐IPD) , X‐ray defined pneumonia among HIV‐1 negative children, and other new outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1990 to Week 4 February 2009); and EMBASE (1974 to March 2009). Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, in children under two with IPD and clinical / radiographic pneumonia as outcomes. Two review authors independently identified studies, extracted data, and evaluated their corresponding risks of bias. Differences were resolved by discussion. Meta‐analysis used the inverse variance method. We identified 11 publications from six RCTs conducted in Africa, US, Philippines and Finland where 57,015 children received PCV; while 56,029 received placebo or another vaccine. Seven publications provided high quality evidence on PCV efficacy against IPD and four provided moderate quality evidence against pneumonia. None of the five trials with all‐cause mortality data were powered to investigate this outcome. Only two trials have data on all‐cause admissions. The main analysis for this review involved HIV‐1 negative children and used the pooled results of random‐effects model, intent‐to‐treat analysis (ITT). Pooled vaccine efficacy (VE) for VT‐IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes‐IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X‐ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all‐cause mortality, 11% (95% CI ‐1% to 21%, P = 0.08). Analysis involving HIV‐1 positive children had similar findings. PCV is effective in preventing IPD, X‐ray defined pneumonia, and clinical pneumonia among HIV‐1 negative and HIV‐1 positive children under two years. The impact was greater for VT‐IPD than for all serotypes‐IPD, and for X‐ray defined pneumonia than for clinical pneumonia. An 11% reduction with a 95% CI of ‐1% to 21% and a P = 0.08 is compatible with reduction in all‐cause mortality. 肺炎鏈球菌接合型疫苗在小於兩歲之兒童中對於疫苗型之侵入性肺炎鏈球菌疾病及X光定義之肺炎的預防 在低收入的國家中，由肺炎鏈球菌造成之肺炎是兒童罹病以及死亡的一大主要原因。肺炎鏈球菌接合型疫苗對於侵襲性肺炎鏈球菌感染症，肺炎以及死亡率的減低效力需要被評估。 此研究目的在於更新2004年發表關於肺炎鏈球菌接合型疫苗預防疫苗同型之侵襲性肺炎鏈球菌感染症，X光定義之肺炎在後天性免疫不全病毒陰性之兒童身上的效力，以及其他新的結果。 我們搜尋了考科藍中心登記之控制試驗(The Conchrane Library 2009, issue 1)，其中包含了考科藍急性呼吸感染群的特定登記(Cochrane Acute Respiratory Infections Group's Specialised Register)，MEDLINE(1990 – 2009二月第四周)以及EMBASE(1974 – 2009三月)。 我們搜尋了考科藍中心登記之控制試驗(The Conchrane Library 2009, issue 1)，其中包含了考科藍急性呼吸感染群的特定登記(Cochrane Acute Respiratory Infections Group's Specialised Register)，MEDLINE(1990 – 2009二月第四周)以及EMBASE(1974 – 2009三月)。 兩個回顧作者獨立地找出研究，分析資料以及評估各自對應的偏差風險。如果有不同的結果，則會互相討論做解決。統合分析則使用變異數倒數法。 我們從六個在非洲，美國，菲律賓以及芬蘭進行的隨機對照實驗中找出了十一篇文章，總共包含了57015個兒童接受了肺炎鏈球菌接合型疫苗，而有56029個兒童接受了安慰劑或是其他的疫苗。七篇文章提供了關於肺炎鏈球菌接合型疫苗針對侵入性肺炎鏈球菌疾病的效力的高品質證據。四篇提供了對於肺炎中等程度的證據。五個隨機對照實驗中沒有任何一個有足夠的考驗力能夠研究這個結果。只有兩個隨機對照實驗有關於所有原因住院的資料。 這篇回顧主要分析包含了後天免疫不全病毒陰性的兒童並且使用了隨機效果模型和意圖治療分析法的整合結果。 整合疫苗效力對於疫苗型的侵入性肺炎鏈球菌疾病是80%(95%信賴區間是58% – 90%，p值小於0.0001);所有血清型之侵入性肺炎鏈球菌疾病是58%(95%信賴區間是29%75%，p值等於0.001);世界衛生組織x光定義肺炎是27%(95%信賴區間是15%36%，p值小於0.0001);臨床上之肺炎是6%(95%信賴區間是2%9%，p值等於0.0006);以及所有原因的死亡率是11%(95%信賴區間是 −1%21%，p值等於0.08)。關於後天免疫不全病毒陽性的兒童有類似的結果。 肺炎鏈球菌接合型疫苗能夠有效預防在小於兩歲之後天免疫不全病毒陽性以及陰性兒童的侵入性肺炎鏈球菌疾病, x光定義肺炎，以及臨床上之肺炎。比起所有血清型之侵入性肺炎鏈球菌疾病，疫苗的使用在疫苗型的侵入性肺炎鏈球菌疾病的影響較大。比起臨床上之肺炎，疫苗的使用在x光定義之肺炎的影響較大。11%的下降幅度，在95%信賴區間是 −1%21%，p值等於0.08下，是跟所有原因死亡率下降符合的。 本摘要由臺灣大學附設醫院李孟叡翻譯。 此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。 針對小於兩歲之兒童身上由肺炎鏈球菌引起的壓倒性血液感染以及肺部感染(肺炎)的疫苗。 在兒童身上，肺炎鏈球菌是壓倒性血液感染以及肺部感染(肺炎)主因之一。越來越多的抗藥性之肺炎鏈球菌在全世界被發現，並且可能降低建議使用之抗生素的效果。類似疫苗這樣的預防措施是必要的。這篇回顧找出了兩篇在美國，兩篇在非洲，一篇在菲律賓，一篇在芬蘭進行的實驗，總共包含了113044位小於兩歲的兒童。在這些研究中，肺炎鏈球菌接合型疫苗能夠預防壓倒性的肺炎鏈球菌血液感染以及肺炎。

The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies.