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This study aimed to describe community-acquired bacterial coinfection (CAI) and antimicrobial use among COVID-19 patients.Electronic records were retrospectively reviewed, and clinical data, laboratory data, antibiotic use, and outcomes of patients with and without CAI were compared.Of 1116 patients, 55.1% received antibiotics within 48 hours, but only 66 (5.9%) had documented CAI, mainly respiratory (40/66, 60.6%). Patients with CAI were more likely to present with myalgia (Overall CAI rate was low (5.9%) and antimicrobial use disproportionately high (55.0%), varying little over time. The mortality rate of coinfected patients was high. Certain parameters can be used to better identify those with CAI and those who need blood cultures.

The aim of this study was to determine the predictors of mortality and describe laboratory trends among adults with confirmed COVID-19.The medical records of adult patients admitted to a referral hospital with COVID-19 were retrospectively reviewed. Demographic and clinical characteristics, and laboratory parameters, were compared between survivors and non-survivors. Predictors of mortality were determined by multivariate analysis. Mean laboratory values were plotted across illness duration.Of 1215 patients, 203 (16.7%) had mild, 488 (40.2%) moderate, 183 (15.1%) severe, and 341 (28.1%) critical COVID-19 on admission. In-hospital mortality was 18.2% (0% mild, 6.1% moderate, 15.8% severe, 47.5% critical). Predictors of mortality were age ≥ 60 years, COPD, qSOFA score ≥ 2, WBC10 × 10The overall mortality rate was high. Predictors of mortality were similar to those of other reports globally. Marked inflammation and worsening pulmonary and renal function were evident among non-survivors by the 2nd-3rd week of illness.

Objectives: To estimate the proportion of TB patients who have access to mobile phones and to describe mobile phone utilization practices of TB patients.Methods: Six public and six private TB clinics representing the four districts of Metro Manila and one institution in Cavite were purposively selected for this cross-sectional survey conducted in 2006. Using an interviewer-administered questionnaire, patients suspected to have TB, those newly diagnosed and those currently on treatment under either DOTS or non-DOTS were interviewed.Results: Of the 337 patients interviewed, 65% (95% CI 60.2 to 70.6) have access to mobile phones (45% currently own a mobile phone and 20% share a mobile phone with a household member). The mean duration of ownership was 1.8 years (SD1.7). Almost all had prepaid subscriptions (99%) and 72% had some credit/load in their mobile phones at the time of interview. Of the three existing networks, subscription to SMART was highest, followed by the Globe network. Most of them use their phones for social purposes and emergency-related communications.Most of the respondents were male (60%) in the age group of 20-39 (54%) and 40-59 years old (33%). Half of the respondents were from public TB clinics (52%). On multivariable analysis, patients consulting in private clinics [OR 2.25, 95% CI 1.36 to 3.74], belonging to the younger age of

Objective. This study aimed to assess compliance with current best practice guidelines on the use of antibiotics in the Department of Surgery in the Philippine General Hospital and to determine the impact of the dissemination of an institution-based guideline on compliance and on patient outcomes. Methods. Two antibiotic use surveys were performed 4 weeks before and 4 weeks after the implementation and dissemination of the PGH Surgical Antibiotic Use Guidelines in the Department of Surgery. The medical records of eligible patients were reviewed regarding patient and case characteristics, details on the administration of antibiotics and the collection of specimen for culture studies. Data relating to the occurrence of surgical site infection within 30 days of the operation was extracted. Compliance with antibiotic use guidelines was assessed for each case. The compliance rates in the pre- and post-intervention periods were compared. Results. The study included a total of 477 patients, 213 in the pre-implementation and 264 in the post implementation period. Compared with the pre-intervention period, rates of compliance with guidelines improved for all parameters in the post-implementation period except for correct dosing. The greatest improvement was seen in the selection of the recommended drug, and proper duration. There was modest improvement in the timing of the preoperative drug administration. There was poor compliance with recommendations for appropriate specimen collection for culture studies, with marked improvement in collection in the pediatric group post intervention. Overall, the in-hospital SSI rate was reduced from 6.8% to 1.1%, while there was little change in the 30-day SSI rate, post-intervention. Conclusion. A simple intervention to raise awareness of institutional guidelines on antibiotic use in the surgical setting lead to a modest improvement on overall compliance, although rates of total compliance with all relevant guidance on antibiotic use, choice, dose, timing and duration remained low. The impact on surgical site infection rates based on such compliance was modest.

Background: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). Methods: PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. Results: 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC + EFV (269) and AZT+3TC + EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58–7.52 p

To describe the clinical profile and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) across the spectrum of disease severity.This retrospective study included adult patients with confirmed COVID-19 infection admitted to a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease severity categories.Of 1500 patients with COVID-19, 14.8% were asymptomatic, 13.5% had mild disease, 36.6% had moderate disease, 12.3% had severe disease and 22.7% had critical disease. Asymptomatic patients were admitted for a concurrent condition or for isolation. Patients aged60 years, male gender and with co-morbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastrointestinal symptoms and decreased sensorium were more common in patients with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. The overall mortality rate was 15.1%. Adopting a symptom-based strategy reduced the length of hospitalization from a median of 13 [interquartile range (IQR) 7-21] days to 9 (IQR 5-14) days.The clinical profile and outcomes for this cohort of patients with COVID-19 was consistent with published reports. Asymptomatic infection was common, and universal testing may be a valuable strategy in the correct context, given the implications for infection control. A symptom-based strategy was found to reduce the length of hospitalization considerably.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

Introduction. In the attempt to control the spread of the disease and the pandemic, numerous COVID-19 vaccines are in development. A review of the evidence on their efficacy and safety are critical. Methods. A search for trials was done using the COVID-19 Living OVerview of Evidence (L·OVE) platform. We also searched for relevant authorization documents and trial reports for COVID-19 vaccines of the US-Food and Drug Authority (US-FDA), the European Medicines Agency (EMA), the United Kingdom Medicines and Health Products Regulatory Agency (MHRA), and the WHO website. We included studies that fulfilled the following inclusion criteria: population – humans; intervention – COVID-19 vaccines; comparison – control or placebo; outcomes – efficacy and adverse events; methods – phase 3 randomized trials. Two reviewers independently screened the reports, assessed the methodological quality, and extracted the data on the trial characteristics and results on vaccine efficacy and safety. The date of last search was March 11, 2021. Results. Interim results of trials investigating five vaccines were identified and included in the review. All five vaccines demonstrated satisfactory vaccine efficacy (VE) against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence: BNT162b2, VE 95% (95% CI 90.3, 97.6); mRNA-1273, VE 93.6% (95% CI 88.6, 96.5); ChAdOx1, VE 66.7% (95% CI 57.4, 74.0), Gam-COVID-Vac, VE 91.1% (95% CI 83.6, 95.1); and Ad26.CoV2.S, VE 67.2% (95% CI 59.3, 73.7). Data on the efficacy against severe COVID-19 infection and asymptomatic COVID-19 infection are still inconclusive, except for Ad26.CoV2.S, which demonstrated good efficacy in preventing moderate and/or severe COVID-19 infection and acceptable protection against asymptomatic COVID-19 infection 28 days after vaccination (moderate certainty of evidence). Efficacy data on preventing death from COVID-19 infection are still inconclusive. Very limited phase 3 trial data is available to inform vaccine efficacy against the different variants of SARS-CoV-2. Vaccination with these five vaccines was associated with higher adverse reactions compared to control. These adverse events, due to reactions to the vaccines, were mild to moderate and of short duration. Available evidence on vaccine efficacy and safety is limited, mainly due to the short follow up and the small sample size of specific populations. Conclusion. BNT162b2, mRNA-1273, ChAdOx1, Gam-COVID-Vac and Ad26.CoV.S vaccines demonstrated satisfactory vaccine efficacy against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence. Data on the efficacy against severe COVID-19 infection, asymptomatic COVID-19 infection, and death from COVID-19 infection are still inconclusive. Long-term efficacy and safety data, and data on the efficacy against variant strains of SARS-CoV-2 are still lacking.

Objectives: To describe the clinical profile and factors associated with mortality among the first 200 patients confirmed to have COVID-19 infection admitted in the University of the Philippines – Philippine General Hospital (UP-PGH) Methodology: We conducted a retrospective review of adult patients with confirmed COVID-19 infection admitted in PGH, a designated COVID-19 referral center. Demographic, clinical data, and clinical outcomes were extracted from medical records. Frequencies and distributions of various clinical characteristics were described, and factors associated with mortality were investigated. Results: Of the 200 patients in our cohort, majority were male (55.5%), and more than half (58%) were over 60 years old. Underlying co-morbid illnesses (67.5%) included hypertension (49.5%), diabetes mellitus (26.5%), and cardiovascular disease (20.5%). Most frequent presenting symptoms were cough (69.0%), fever (58.5%), or shortness of breath (53.0%). Most patients presented with mild (n=41, 20.5%) to moderate illness (n=99, 49.5%) and only 60 were considered severely (n=32, 16.0%) or critically ill (n=28, 14.0%). Many (61%) received empiric antibiotics, while 44.5% received either repurposed drugs or investigational therapies for COVID-19. Bacterial co-infection was documented in 11%, with Klebsiella pneumoniae commonly isolated. In-hospital mortality was 17.5%, which was highest for critical COVID-19 (71.4%). Mortality was observed to be higher among patients age 60 and above, those requiring oxygen, ventilatory support and ICU admission, and among those who developed acute kidney injury, acute stroke, sepsis, and nosocomial pneumonia. Conclusion: Our study confirms that COVID-19 affects males, older individuals and those with underlying co-morbid conditions. Empiric antimicrobial treatment was given for majority of patients, despite documentation of bacterial infection in only 11%. K. pneumoniae was commonly isolated, reflecting local epidemiology. Mortality rate during this early period of the pandemic was high and comparable to other institutions. Factors associated with mortality were related to critical COVID-19 and are similar to other studies.

The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.351 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

Setting The 3rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable. Objective To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016. Design In March–December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive. Results There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350−518) for smear-positive TB, and 1,159 (95% CI: 1,016−1,301) for bacteriologically confirmed TB. Conclusion This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.

Hongchao Pan (University of Oxford. Nuffield Department of Population Health. Medical Research Council Population Health Research Unit. Oxford, United Kingdom); Richard Peto (University of Oxford. Nuffield Department of Population Health. Medical Research Council Population Health Research Unit. Oxford, United Kingdom); Ana-Maria Henao-Restrepo (World Health Organization. Geneva, Switzerland); Marie-Pierre Preziosi (World Health Organization. Geneva, Switzerland); Vasee Sathiyamoorthy (World Health Organization. Geneva, Switzerland); Quarraisha Abdool Karim (Centre for the AIDS Programme of Research in South Africa. Durban, South Africa); Marissa M. Alejandria (University of the Philippines. National Institutes of Health. Institute of National Epidemiology. Manila, Philippines); Cesar Hernandez Garcia (Spanish Agency of Medicines and Medical Devices. Madrid, Spain / Hospital Clinico San Carlos. Madrid, Spain); Marie-Paule Kieny (Institut National de la Sante et de la Recherche Medicale. Paris, France); Reza Malekzadeh (Tehran University of Medical Sciences. Digestive Disease Research Institute. Tehran, Iran); Srinivas Murthy (University of British Columbia. Vancouver, Canada); K. Srinath Reddy (Public Health Foundation of India. New Delhi, India); Mirta Roses Periago (National Academy of Sciences of Buenos Aires. Buenos Aires, Argentina); Pierre Abi Hanna (Rafic Hariri University Hospital. Beirut, Lebanon); Florence Ader (Hospices Civils de Lyon. Lyon, France); Abdullah M. Al-Bader (Ministry of Health. Kuwait City, Kuwait); Almonther Alhasawi (Infectious Diseases Hospital. Kuwait City, Kuwait); Emma Allum (University of Bristol. Bristol, United Kingdom); Athari Alotaibi (Ministry for Preventive Health. Riyadh, Saudi Arabia); Carlos A. Alvarez-Moreno (Universidad Nacional de Colombia. Bogota, Colombia / Clinica Colsanitas. Bogota, Colombia); Sheila Appadoo (University of Bern. Bern, Switzerland); Abdullah Asiri (Ministry for Preventive Health. Riyadh, Saudi Arabia); Pal Aukrust (Oslo University Hospital. Oslo, Norway); Andreas Barratt-Due (Oslo University Hospital. Oslo, Norway); Samir Bellani (University of Bristol. Bristol, United Kingdom); Mattia Branca (University of Bern. Bern, Switzerland); Heike B.C. Cappel-Porter (University of Bristol. Bristol, United Kingdom); Nery Cerrato (Secretaria de Salud de Honduras. Tegucigalpa, Honduras); Ting S. Chow (Penang Hospital. Penang, Malaysia); Najada Como (University Hospital Center "Mother Teresa". Tirana, Albania); Joe Eustace (University College Cork. HRB Clinical Research Facility. Cork, Ireland); Patricia J. Garcia (Universidad Peruana Cayetano Heredia. Lima, Peru); Sheela Godbole (Indian Council of Medical Research. New Delhi, India / National AIDS Research Institute. Pune, Maharashtra, India); Eduardo Gotuzzo (Universidad Peruana Cayetano Heredia. Lima, Peru); Laimonas Griskevicius (Vilnius University Hospital Santaros Klinikos. Vilnius, Lithuania); Rasha Hamra (Ministry of Public Health. Beirut, Lebanon); Mariam Hassan (Shaukat Khanum Memorial Cancer Hospital and Research Centre. Lahore, Pakistan); Mohamed Hassany (National Hepatology and Tropical Medicine Research Institute. Cairo, Egypt); David Hutton (University of Bristol. Bristol, United Kingdom); Irmansyah Irmansyah (National Institute of Health Research and Development. Jakarta, Indonesia); Ligita Jancoriene (Vilnius University. Faculty of Medicine. Institute of Clinical Medicine. Vilnius, Lithuania); Jana Kirwan (University of Bristol. Bristol, United Kingdom); Suresh Kumar (Sungai Buloh Hospital. Selangor, Malaysia / Jalan Hospital. Selangor, Malaysia); Peter Lennon (Department of Health and Children. Dublin, Ireland); Gustavo Lopardo (Fundacion del Centro de Estudios Infectologicos. Buenos Aires, Argentina); Patrick Lydon (World Health Organization. Geneva, Switzerland); Nicola Magrini (Italian Medicines Agency. Rome, Italy); Teresa Maguire (Department of Health and Children. Dublin, Ireland); Suzana Manevska (Ministry of Health. Skopje, North Macedonia); Oriol Manuel (Lausanne University Hospital. Lausanne, Switzerland); Sibylle McGinty (University of Bern. Bern, Switzerland); Marco T. Medina (Universidad Nacional Autonoma de Honduras. Tegucigalpa, Honduras); Maria L. Mesa Rubio (Ministry of Health. Bogota, Colombia); Maria C. Miranda-Montoya (World Health Organization. Geneva, Switzerland); Jeremy Nel (University of the Witwatersrand. Johannesburg, South Africa); Estevao Portela Nunes (Fundacao Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil); Markus Perola (National Institute for Health and Welfare of Finland. Helsinki, Finland / University of Finland. Helsinki, Finland); Antonio Portoles (Universidade Complutense de Madrid. Madrid, Spain / Spanish Clinical Research Network. Madrid, Spain / Hospital Clinico San Carlos. Instituto de Investigacion Sanitaria San Carlos. Madrid, Spain); Menaldi R. Rasmin (Rumah Sakit Umum Pusat Persahabatan. Jakarta, Indonesia); Aun Raza (Shaukat Khanum Memorial Cancer Hospital and Research Centre. Lahore, Pakistan); Helen Rees (Wits Reproductive Health and HIV Institute. Johannesburg, South Africa); Paula P. S. Reges (Fundacao Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil); Chris A. Rogers (University of Bristol. Bristol, United Kingdom); Kolawole Salami (World Health Organization. Geneva, Switzerland); Marina I. Salvadori (Public Health Agency of Canada. Ottawa, Canada); Narvina Sinani (National Agency for Medicines and Medical Devices. Tirana, Albania); Jonathan A. C. Sterne (University of Bristol. Bristol, United Kingdom); Milena Stevanovikj (University Clinic of Infectious Diseases and Febrile Conditions. Skopje, North Macedonia); Evelina Tacconelli (University of Verona. Verona, Italy); Kari A. O. Tikkinen (Helsinki University Hospital. Helsinki, Finland / South Karelian Central Hospital. Lappeenranta, Finland); Sven Trelle (University of Bern. Bern, Switzerland); Hala Zaid (Ministry of Health and Population. Cairo, Egypt); John-Arne Rottingen (Research Council of Norway. Oslo, Norway); Soumya Swaminathan (World Health Organization. Geneva, Switzerland).

Objectives. To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3. Methods. We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups. Results. Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p200 cells/mm3. More adverse effects were also seen in the CP group.

To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naive patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, N = 365; LPH, N = 442; BMH, N = 384; and PGH, N = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/μL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). Mycobacterium tuberculosis (TB) was most common at PGH (N = 75) but was rare at NMC (N = 4). Pneumocystis pneumonia (PCP) prevalence was highest at NMC (N = 74) and lowest at BMH (N = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6?122.1), BMH (aOR = 12.6, CI = 3.9?40.3), and LPH (aOR = 6.6, CI = 2.1?21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04?0.2) and LPH (aOR = 0.2, CI = 0.1?0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9?41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naive patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted., The American Journal of Tropical Medicine and Hygiene, 97(1), pp.49-56; 2017

BACKGROUND Atopic dermatitis is the most common chronic skin disease affecting the pediatric population. Probiotics have been proposed to be effective in preventing the development of pediatric atopic dermatitis. Although studies show promise for the use of probiotics, the evidence is still inconclusive due to significant heterogeneity and imprecision. OBJECTIVE To determine the comparative effectiveness of the different types of probiotic strains in preventing the development of atopic dermatitis among pediatric patients. METHODOLOGY A systematic search of Cochrane Library, MEDLINE, TRIP Database, and Centre for Research and Dissemination was conducted. Manual search of the reference lists and search for unpublished articles were also done. All randomized controlled trials available from inception until April 12, 2020, on the use of probiotics in the prevention of atopic dermatitis among children were included. The comparator groups considered are other probiotic strains and placebo. The primary outcome of interest was the development of atopic dermatitis. Two authors independently searched for articles, screened the articles for inclusion, appraised the articles using the Cochrane risk of bias tool version 2, and extracted the data. In case of disagreement, the two authors discussed the source of disagreement until consensus was reached. If consensus was not reached, an independent third party reviewer was consulted. Frequentist network meta-analysis was conducted using STATA 14 software. The ranking probabilities and surface under the cumulative ranking curve (SUCRA) values were obtained to determine ranking of the different probiotic strains based on efficacy and safety data. RESULTS We included 21 original studies represented by 35 records and a total of 5406 children with atopic dermatitis as diagnosed by clinicians or fulfillment of validated diagnostic criteria. All studies were randomized placebo-controlled trials. The top 3 probiotic preparations in terms of efficacy in reducing the risk of atopic dermatitis are Mix8 (Lactobacillus paracasei ST11, Bifidobacterium longum BL999), LP (Lactobacillus paracasei ssp paracasei F19) and Mix3 (Lactobacillus rhamnosus GG, Bifidobacterium animalis ssp lactis Bb-12). Mix8 compared with placebo probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.46, 95% CI 0.25-0.85). Mix3 compared with placebo also probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.50, 95% CI 0.27-0.94). It is uncertain whether LP compared with placebo reduces the risk of atopic dermatitis due to very-low-quality certainty of evidence (RR = 0.49, 95% CI 0.20-1.19). In terms of adverse events, LGG may slightly lead to less adverse events compared with placebo based on low-quality evidence (RR = 0.70, 95% CI 0.32-1.52). Mix4 may slightly lead to more adverse events compared with placebo based on low-quality evidence (RR = 1.06, 95% CI 0.02-51.88). Based on subgroup analysis of studies involving infants, Mix3 compared with placebo probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.46, 95% CI 0.22-0.97). In the subgroup analysis of studies where probiotics were administered to pregnant women and to infants, LRH compared with placebo probably reduces the risk of atopic dermatitis based on moderate-quality evidence (RR = 0.54, 95% CI 0.26-1.11). CONCLUSION Certain probiotic preparations demonstrate efficacy in reducing the risk of developing atopic dermatitis when administered to pregnant women, infants, or both.

Primary intracranial leiomyosarcoma (PIL) is a rare non-infectious aetiology of focal mass lesions among HIV-infected individuals. With only 16 published cases worldwide, information on its pathophysiology, risk factors, clinical course and management options is limited. We report two cases of PIL in HIV-infected Filipino men who presented with 1–3 months history of persistent headache, progressing in severity. Both had cranial MRI revealing intracranial mass diagnosed as leiomyosarcoma by excision biopsy and immunohistochemical staining. Both patients underwent adjuvant cranial radiotherapy and chemotherapy. Biologics were initiated in one patient. Both patients were alive with evidence of the disease.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To assess the effects of different dosing regimens of praziquantel in terms of clinical cure, parasitological cure, and parasite egg reduction. 2. To assess the effects of artemisinin derivatives compared to praziquantel alone or in combination, in terms of clinical cure, parasitological cure, and parasite egg reduction. 3. To assess the effects of praziquantel and artemisinin derivatives, alone or in combination, in preventing S. japonicum infections among at risk population groups.

Objective. This study aimed to describe dengue burden in the Philippines. Specifically, health and economic costs of the disease were estimated. Methods. A published serotype-specific and age-stratified dengue dynamic transmission model was populated with Philippine-specific dengue epidemiology and cost data. Data were gathered from literature and record reviews. Dengue experts were consulted to validate the model parameters. Sensitivity analyses were performed to test the uncertainty of input parameters on model outcomes. Results. By 2016 to 2020, it is estimated that annually, average hospitalized cases will amount to 401,191 and ambulatory cases will amount to 239,497; resulting to USD 139 million (PhP 5.9 billion) and USD 19 million (PhP 827 million) worth of aggregate costs shouldered by the public payer for hospitalized and ambulatory cases, respectively. Average annual productivity losses may amount to USD 19 million (PhP 821 million) and DALY lost is expected to be 50,622. Conclusion. The cost of dengue is high especially since the Philippines is an endemic country. Thus, there is a need to optimize government interventions such as vector control and vaccination that aim to prevent dengue infections.

Background Small non-coding microRNAs (miRNAs) are increasingly recognized as key regulators of the host response to sepsis. However, the molecular mechanisms implicated in the role of miRNAs during sepsis progression is still unclear. It is hypothesized that differentially expressed genes in septic patients with worse outcomes are associated with dysregulation of miRNA expression. This study aimed to identify specific miRNA-gene pairs that may be implicated in the development of shock and renal failure in sepsis. Methods miRNA from serum and RNA from PBMCs were acquired from n = 40 participants in a prospective cohort of Filipino septic patients: n = 15 developed septic shock and n = 17 developed renal failure. RT-qPCR was done to measure the expression of 21 sepsis-associated miRNAs. Differentially expressed miRNAs (DEMs) for each outcome was identified, followed by gene target prediction for each DEM. Gene expression microarrays covering 18,616 genes were also performed to identify differentially expressed genes (DEGs; P < 0.05, log FC> |0.3|) for each outcome. Significant miRNA-gene pairs were selected by evaluating the overlap of the predicted gene targets of the DEMs with the DEGs for each corresponding outcome. Given the gene-silencing mechanism of miRNAs, overlap analysis was performed on only the downregulated DEGs when the specific DEM was upregulated (and vice versa). Results Septic participants who developed shock, compared with those who did not, had higher expression of 1 DEM, miR-223-5p, and downregulation of 20 DEGs. NUS1 was the only predicted gene target of miR-223-5p that was also downregulated in septic shock. Participants who developed renal failure, vs. those who did not, had lower expression 6 DEMs and upregulation of 6 DEGs. KPNA4 is a gene target of the DEMs, miR-126-5p, and miR-181a-5p, that was also upregulated in renal failure. Conclusion Significant miRNA–gene pairs related to worse clinical outcomes in sepsis were identified: miR-223-5p with NUS1 for shock and either miR-126-5p or miR-181-5p with KPNA4 for renal failure. While the biological significance of these miRNA-gene pairs still needs to be evaluated, these findings can potentially help future efforts in developing prognostic markers or therapeutic targets for shock and renal failure in sepsis. Disclosures All authors: No reported disclosures.

Background Polyradiculopathy (PRP) and encephalitis are neurologic syndromes associated with 1% of cytomegalovirus (CMV) disease among patients with advanced HIV infection. Untreated patients die within 8 weeks. This case series and literature review highlights the clinical and laboratory features integral to the prompt diagnosis and treatment of these rare but serious manifestations of CMV disease among AIDS patients. Methods We document CMV PRP and encephalitis in two HIV-seropositive men seen in a tertiary hospital in the Philippines. Both patients presented with bilateral leg weakness, paresthesias, hyporeflexia, and urinary retention associated with confusion and memory lapses. In the two cases described, diagnosis of CMV disease was delayed because it was not immediately entertained. Tuberculosis involving the nervous system was first ruled out. Results The first case was a 31-year-old male with a baseline CD4 count of 9 cells/mm3 who presented with signs and symptoms of bilateral leg weakness and paresthesias 3 weeks after initiation of antiretrovirals (ART). CMV viremia was detected by PCR. Ganciclovir was initiated late, and he subsequently died of multiorgan failure. The second case is a 29-year-old male with a baseline CD4 count of 2 cells/mm3. CMV DNA PCR was detected in the CSF. He died prior to initiation of anti-CMV therapy. Conclusion CMV-related neurologic complications are uncommon, but often fatal when appropriate anti-CMV therapy is not initiated promptly. The diagnosis of CMV PRP should be considered in patients with advanced immunosuppression presenting with ascending paraplegia, areflexia, and urinary retention with typical CSF abnormalities (polymorphonuclear pleocytosis, elevated protein concentration, and hypoglycorrhachia). Table 1. Summary of Presenting Signs and Symptoms of the Two Cases in Comparison to the 103 Patients with CMV PRP in Anders and Goebel’s Review Sign or Symptom Anders and Goebel [2] Case 1 Case 2 Lower limb weakness 100% Present Present Lower limb areflexia 100% Present Present Urinary retention 94% Present Present Paresthesia 79% Present Present Sensory loss (legs) 72% Present Present Fecal incontinence 67% Absent Absent Lumbar pain 36% Absent Absent Babinski sign 16% Absent Absent Disclosures All authors: No reported disclosures.

Background Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. Methods We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. Results ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. Conclusion ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. Disclosures All authors: No reported disclosures.

Objective This article's objective was to describe the processes, strategies, and challenges of community-based recruitment to complement hospital-based recruitment for a global clinical outcomes trial on chronic obstructive pulmonary disease (COPD). Study Design and Setting To increase the subject recruitment for the clinical research, field staff were trained on community-based recruitment strategies and activities. Courtesy calls and coordination with community organizations were done before recruitment activities. House-to-house interviews using patient referral checklist, lay fora on COPD, and spirometry camps identified eligible participants in five sites in the Philippines. Results Of 3,202 individuals interviewed, 27% potentially eligible were referred to hospital sites. Of 55% who were successfully screened, 9% were randomized. Courtesy calls and endorsements identified potential recruits. Issues related to communication, work, health condition, and family members' encouragement affected participation. Complexity of the eligibility criteria contributed to the high screen failure rates. Enabling full subject protection entitlements before informed consent taking was one of the ethical issues identified. Conclusions Community-based recruitment may increase the number of subjects for clinical trials depending on the complexity of the requirements. Adopting a community-based recruitment strategy must be decided at the planning stage for efficient coordination of activities. Social preparation should consider socioeconomic and cultural factors. Current ethical guidelines and regulations indirectly address issues on community-based recruitment.

Bloodstream infections caused by Candida species are of increasing importance and associated with significant mortality. We performed a multi-centre prospective observational study to identify the species and antifungal susceptibilities of invasive bloodstream isolates of Candida species in the Asia-Pacific region. The study was carried out over a two year period, involving 13 centers from Brunei, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. Identification of Candida species was performed at each study center, and reconfirmed at a central laboratory. Susceptibility testing was performed using a commercial broth dilution panel (Sensititre YeastOne YST-010, Thermofisher, United Kingdom) with susceptibility categorisation (S = susceptible, S-DD = susceptible dose-dependent) applied using breakpoints from the Clinical Laboratory Standards Institute. Eight hundred and sixty-one Candida isolates were included in the study. The most common species were C. albicans (35.9%), C. tropicalis (30.7%), C. parapsilosis (15.7%), and C. glabrata (13.6%). Non-albicans species exceeded C. albicans species in centers from all countries except Taiwan. Fluconazole susceptibility was almost universal for C. albicans (S = 99.7%) but lower for C. tropicalis (S = 75.8%, S-DD = 6.1%), C. glabrata (S-DD = 94.9%), and C. parapsilosis (S = 94.8%). Echinocandins demonstrated high rates of in vitro susceptibility (S>99%) against C. albicans, C. tropicalis, and C. parapsilosis This study demonstrates that non-albicans species are the most common isolates from bloodstream infections in most countries in the Asia-Pacific region, with C. tropicalis as the predominant species. Because of the prevalence of reduced susceptibility to fluconazole in non-albicans species, the study indicates that echinocandins should be the antifungal of choice in clinically unstable or high-risk patients with documented candidemia.

Urinary tract infections (UTIs) are among the most prevalent infectious diseases in the general population. They cause a substantial financial burden in the community and are associated with significant morbidity and mortality, particularly in hospitals. With increased rates of antimicrobial resistance, especially in the Asia-Pacific region, treatment of complicated UTIs (cUTIs) can be challenging for clinicians. Consideration of an optimal antimicrobial agent should be based on local resistance patterns, patient-specific factors, pharmacokinetic and pharmacodynamic principles, and cost. In the Asia-Pacific region, nearly half of Escherichia coli urinary isolates were resistant (including intermediate and resistant) to levofloxacin or ciprofloxacin and ≥30% were resistant to third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) and cefepime. Overall, 33% of urinary E. coli isolates exhibited extended-spectrum β-lactamase (ESBL)-producing phenotypes. Prevalence of ESBL-producing urinary E. coli was highest in India (60%), followed by Hong Kong (48%) and Singapore (33%). All urinary isolates of E. coli were susceptible to both ertapenem and imipenem. All urinary isolates of Klebsiella pneumoniae were susceptible to imipenem and 4% of them were resistant to ertapenem. Care should be exercised when using trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and cephalosporins for the empirical treatment of UTIs, particularly cUTI among moderately to severely ill patients. Empiric antimicrobial treatment for serious cUTIs in which risk factors for resistant organisms exist should include broad-spectrum antibiotics such as carbapenems (ertapenem, imipenem, meropenem, and doripenem) and piperacillin-tazobactam. Aminoglycosides, tigecycline, and polymyxins (colistin or polymyxin B) can be used for the treatment of multidrug-resistant organisms or serious cUTIs when first-line options are deemed inappropriate or patients fail therapy. Because of considerable variability in different countries, local epidemiological data is critical in the effective management of UTIs in the Asia-Pacific region.

Background Reminder systems and late patient tracers as strategies to improve patients' adherence to tuberculosis screening, diagnosis, and treatment are used in some countries, but their effectiveness has not previously been systematically reviewed. Objectives To assess the effects of reminder systems and late patient tracers on completion of diagnostics, commencement of treatment in people referred for curative or prophylactic treatment of tuberculosis, completion of treatment in people starting curative or prophylactic treatment for tuberculosis, and cure in people being treated for active tuberculosis. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register (June 2008), Cochrane Effective Practice and Organization of Care Group Specialized Register (April 2007), CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE (1966 to June 2008), EMBASE (1974 to June 2008), LILACS (1982 to June 2008), CINAHL (1982 to June 2008), SCI-EXPANDED (1945 to June 2008), SSCI (1956 to June 2008), mRCT (June 2008), Indian Journal of Tuberculosis (1983 to June 2008), and reference lists. We also contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing any reminders or late patient tracers with no or other kinds of reminders or late patient tracers. We included people in any setting who require treatment for tuberculosis or require prophylaxis against tuberculosis and are referred to tuberculosis diagnostic or screening services. Data collection and analysis Two authors independently assessed trial risk of bias and extracted data. No meta-analysis could be undertaken due to the heterogeneity of interventions across trials. Main results Nine trials involving 5257 participants met the inclusion criteria. Three assessed the use of late patient tracers, and six assessed reminder systems. Late patient tracers (home visit and letter) were shown to be beneficial in increasing adherence to tuberculosis treatment compared with no late patient tracer. The results from almost all the reminder trials, except one, show benefits of different types of reminders compared to no reminder on adherence to tuberculosis clinic appointments. Authors' conclusions The included trials show significantly better outcomes among those tuberculosis patients for which late patient tracers and reminders are used. Studies of good quality (large and with rigorous study design) are needed to decide the most effective late patient tracer actions and reminders in different settings. Future studies of reminders in chemoprophylaxis and treatment settings would be useful. Plain Language Summary Reminder systems and late patient tracers in the diagnosis and management of tuberculosis This review aimed to assess the effects of reminder systems and late patient tracers on patients' adherence to medical advice (such as attending clinic appointments for taking anti-tuberculosis drugs) and on clinical outcomes (such as cure of tuberculosis) in the following situations: treatment for active tuberculosis; tests for diagnosis of tuberculosis; and treatment to prevent tuberculosis in high-risk individuals. Reminder systems are used before a clinic or drug-collection appointment to remind patients to attend the appointment, or sometimes during treatment at home to remind patients to take their drugs. Late patient tracers are similar interventions undertaken when patients fail to keep an appointment to encourage them to return to treatment. The review found nine trials involving 5257 participants. Six trials assessed reminder systems and three trials assessed the use of late patient tracers. The results from five of the six reminder trials showed benefits. Trials of late patient tracers (home visits and letters) also showed benefits of the intervention in increasing adherence to tuberculosis treatment. Hence, overall, the results showed better outcomes among those patients for whom reminders or late patient tracers were used.

ObjectivesThe objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies.MethodsA cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty.ResultsWith universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program.ConclusionThe inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers.

Summary Background: In many parts of Asia, the inaccessibility and high cost of diagnostic tests have hampered the study of community-acquired pneumonia (CAP) caused by atypical respiratory pathogens. Objective: This surveillance study examined the frequency of infection with Mycoplasma pneumoniae , Chlamydophila pneumoniae , and Legionella pneumophila in 1756 patients presenting with signs and symptoms of CAP at 12 medical centres in Asia, using standardised laboratory techniques and interpretation criteria in all participating centres. Methods: Diagnosis of current infection was based on significant changes in antibody titer or persisting high antibody titers, together with the presence of bacterial DNA in respiratory secretions, in the case of M. pneumoniae and C . pneumoniae infections, or bacterial antigen in urine, in the case of L. pneumophila serogroup 1 infection. Results: Using these criteria, results from 1374 patients with paired sera showed that, overall, 23.5% of CAP cases were associated with infection with atypical respiratory pathogens, with M. pneumoniae , C. pneumoniae , and L . pneumophila being found in 12.2%, 4.7%, and 6.6% of cases, respectively. Persisting high antibody titers indicative of past exposure to M. pneumoniae , C. pneumoniae , and L. pneumophila were seen in 10.2%, 4.8%, and 18.9% of patients, respectively. Conclusion: These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP.

Background The WHO-recommended regimen for antiretrovirals (ARVs) is tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV), based on demonstrated superiority of TDF+FTC+EFV over zidovudine (AZT) +FTC+ EFV in clinical trials. However, there are reports of increasing TDF resistance in non-B subtypes. We have previously shown that HIV genotypes in the Philippines have shifted (https://idsa.confex.com/idsa/2014/webprogram/Paper45090.html) from B to CRF01_AE. We compared failure rates for ARVs during an acquired drug-resistance surveillance study. Methods We analyzed ARV data from a study with the Department of Health on treatment failure in Filipinos after one year of treatment. Institutional Board Review approval and informed consent were obtained. Results 513 adult patients from 3 national treatment hubs (Philippine General Hospital, San Lazaro Hospital, Vicente Sotto Memorial Medical Center) were enrolled and analyzed. Treatment failure (viral load>1000 copies/mL) at one year for specific regimens are summarized in Table 1. No baseline genotyping was available. 53 (10.3%) patients failed treatment. Genotypes among these were CRF01_AE (87%), B (11%) and C (2%). TDF-containing regimens had significantly higher failure rates (43/303;14.2%) than AZT-containing regimens (10/209;4.5%) (P < 0.001). Failure rates for NVP-based regimens (13/85;15.3%) vs. EFV-based regimens (40/424; 9.4%) were not significantly different (P = 0.1064). The most durable regimen (with >3 patients) was AZT+3TC+EFV, and the worst regimen was TDF+3TC+NVP (P < 0.001). Failure rates for TDF+3TC+EFV were significantly higher than for AZT+3TC+EFV (P = 0.0029). There was no significant difference in adherence (P = 0.5531). 53% of unsuppressed patients had a TDF-resistance mutation, compared with 8% for AZT (P < 0.001). Conclusion TDF-containing regimens were associated with higher treatment failure rates in our CRF01_AE-predominant HIV epidemic. WHO recommendations for treatment may need be revisited for non-B subtypes. Disclosures E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium

Background\ud \ud People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment.\ud \ud Objectives\ud \ud To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes.\ud \ud Search methods\ud \ud We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice and Organization of Care Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, mRCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field.\ud \ud Selection criteria\ud \ud Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment.\ud \ud Data collection and analysis\ud \ud Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach.\ud \ud Main results\ud \ud Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests. We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or 'default' reminders (telephone calls, letters, or home visits to people who had missed an appointment).\ud \ud For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls (clinic attendance: 66% versus 50%; RR 1.32, 95% CI 1.10 to 1.59, one trial (USA), 615 participants, low quality evidence; TB treatment completion: 100% versus 88%; RR 1.14, 95% CI 1.02 to 1.27, one trial (Thailand), 92 participants, low quality evidence). Clinic attendance and TB treatment completion were also higher with default reminders (letters or home visits) (clinic attendance: 52% versus 10%; RR 5.04, 95% CI 1.61 to 15.78, one trial (India), 52 participants, low quality evidence; treatment completion: RR 1.17, 95% CI 1.11 to 1.24, two trials (Iraq and India), 680 participants, moderate quality evidence).\ud \ud For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls (63% versus 48%; RR 1.30, 95% CI 1.07 to 1.59, one trial (USA), 536 participants); and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits (93% versus 65%, one trial (Spain), 318 participants).\ud \ud For people undergoing screening for TB, three trials of pre-appointment phone-calls found little or no effect on the proportion of people returning to clinic for the result of their skin test (three trials, 1189 participants, low quality evidence), and two trials found little or no effect with take home reminder cards (two trials, 711 participants). All four trials were conducted among healthy volunteers in the USA.\ud \ud Authors' conclusions\ud \ud Policies of sending reminders to people pre-appointment, and contacting people who miss appointments, seem sensible additions to any TB programme, and the limited evidence available suggests they have small but potentially important benefits. Future studies of modern technologies such as short message service (SMS) reminders would be useful, particularly in low-resource settings.

Background Cervical cancer is the second leading cause of cancer cases and deaths among Filipino women because of inadequate access to screening and treatment services. This study aims to evaluate the health and economic benefits of HPV vaccination and its combination with different screening strategies to find the most optimal preventive strategy in the Philippines. Methods A cost-utility analysis was conducted using an existing semi-Markov model to evaluate different screening (i.e., Pap smear, visual inspection with acetic acid) and vaccination strategies against HPV infection implemented alone or as part of a combination strategy at different coverage scenarios. The model was run using country-specific epidemiologic, cost and clinical parameters from a health system perspective. Sensitivity analysis was performed for vaccine efficacy, duration of protection and costs of vaccination, screening and treatment. Results Across all coverage scenarios, VIA has been shown to be a dominant and cost-saving screening strategy with incremental cost-effectiveness ratio (ICER) ranging from dominant to Php 61,059 (1443 USD) per QALY gained. VIA can reduce cervical cancer cases and deaths by 25 %. Pap smear screening was found to be not cost-effective due to its high cost in the Philippines. Adding HPV vaccination at a cost of 54 USD per vaccinated girl on top of VIA screening was found to be potentially cost-effective using a threshold of 1 GDP per capita (i.e., Php 120,000 or 2835 USD/ QALY) with the most favorable assumption of providing lifelong immunity against high-risk oncogenic HPV types 16/18. The highest incremental QALY gain was achieved with 80 % coverage of the combined strategy of VIA at 35 to 45 years old done every five years following vaccination at 11 years of age with an ICER of Php 33,126 (783 USD). This strategy may result in a two-thirds reduction in cervical cancer burden. HPV vaccination is not cost-effective when vaccine protection lasts for less than 20 years. Conclusion High VIA coverage targeting women aged 35–45 years old at five-year intervals is the most efficient and cost-saving strategy in reducing cervical cancer burden in the Philippines. Adding a vaccination program at high coverage among 11-year-old girls is potentially cost-effective in the Philippines assuming a life-long duration of vaccine efficacy. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2046-1) contains supplementary material, which is available to authorized users.

Due to a USAID-funded study on blood banks, a national policy was instituted in 1994 that set standards for Philippine blood services, promoted voluntary donation, and led to a ban on commercial blood banks. In this follow-up study, we assess the safety of the supply by determining the residual risk for transfusion-transmitted infections (syphilis, hepatitis B and C, HIV). We also identified unsafe facility practices and generated policy recommendations. A 1992 study found that transfusion-ready blood was not safe using the LQAS method (P > 0.05). We found that the 2012 residual risk became 0 to 0.9 percent attributable to the national policy. We noted poor to fair adherence to this policy. We identified unsafe practices such as use of rapid tests and lack of random blood retesting. Training and use of regional networks may improve safety. Despite improvement in safety, facilities complain of funding and logistical issues regarding compliance with the policy.

This study described the clinical features and complications of leptospirosis among patients seen at nine tertiary hospitals from September 28 to November 30, 2009 after a heavy rainfall typhoon. The clinical findings of the confirmed cases were compared with the previous clinical studies on seasonal leptospirosis in the Philippines. Risk factors for complicated disease were also identified. Confirmed cases were based on any of the following: positive leptospiral cultures of blood or urine, single high leptospira microscopic agglutination test (MAT) titer of 1:1,600, a fourfold rise in MAT, and/or seroconversion. Of 670 patients with possible leptospirosis, 591 were probable by the WHO criteria, 259 (44%) were confirmed. Diagnosis was confirmed by MAT 176 (68%), by culture 57 (22%), and by MAT and culture 26 (10%). The mean age of the confirmed cases was 38.9 years (SD 14.3). The majority were males (82%) and had a history of wading in floodwaters (98%). The majority of the patients presented with nonspecific signs, with fever as the most common (98.5%). Other findings were myalgia (78.1%), malaise (74.9%), conjunctival suffusion (59.3%), oliguria (56.6%), diarrhea (39%), and jaundice (38%). Most of the patients presented with a moderate-to-severe form of leptospirosis (83%). Complications identified were renal failure (82%), pulmonary hemorrhage (8%), meningitis (5%), and myocarditis (4%). Mortality rate was 5%, mostly due to pulmonary hemorrhage. This study emphasizes the importance of public awareness and high index of suspicion among clinicians of leptospirosis during the monsoon months when flooding is common. Early recognition and detection of the disease should decrease morbidity and mortality.

Background Mortality from sepsis and septic shock remains high. Results of trials on intravenous immunoglobulins (IVIG) as adjunctive therapy for sepsis have been conflicting. This is an update of a Cochrane review that was originally published in 1999 and updated in 2002 and 2010. Objectives To estimate the effects of IVIG as adjunctive therapy in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (1966 to December 2012), and EMBASE (1988 to December 2012). We contacted investigators in the field for unpublished data. The original search was performed in 1999 and updated in 2002 and 2008. Selection criteria We included randomized controlled trials comparing IVIG (monoclonal or polyclonal) with placebo or no intervention in patients of any age with bacterial sepsis or septic shock. Data collection and analysis Two authors independently assessed the studies for inclusion and undertook methodologic quality assessment and data abstraction. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. Main results We included 43 studies that met our inclusion criteria in this updated review out of 88 potentially eligible studies. The studies included a large polyclonal IVIG trial in neonates that was concluded in 2011 and classified as ongoing in the 2010 version of this review. Pooled analysis of polyclonal and monoclonal IVIG was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal IVIG trials (n = 1430) and seven trials on IgM-enriched polyclonal IVIG (n = 528) showed significant reductions in mortality in adults with sepsis compared to placebo or no intervention (relative risk (RR) 0.81; 95% confidence interval (CI) 0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis of polyclonal IVIG in neonates, which now includes the recently concluded large polyclonal IVIG trial, showed no significant reduction in mortality for standard IVIG (RR 1.00; 95% CI 0.92 to 1.08; five trials, n = 3667) and IgM-enriched polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; three trials, n = 164). Sensitivity analysis of trials with low risk of bias showed no reduction in mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; five trials, n = 945) and neonates (RR 1.01; 95% CI 0.93 to 1.09; three trials, n = 3561). Mortality was not reduced among patients (eight trials, n = 4671) who received anti-endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti-cytokines (nine trials, n = 7893) demonstrated a marginal reduction in mortality (RR 0.92; 95% CI 0.86 to 0.97). Authors' conclusions Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates with sepsis, there is sufficient evidence that standard polyclonal IVIG, as adjunctive therapy, does not reduce mortality based on the inclusion of the large polyclonal IVIG trial on neonates. For Ig-M enriched IVIG, the trials on neonates and adults were small and the totality of the evidence is still insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice andOrganization of Care Group Specialized Register, CENTRAL,MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, m RCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach. Main results Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests.We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or'default' reminders (telephone calls, letters, or home visits to people who had missed an appointment). For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls (clinic attendance: 66% versus 50%; RR 1.32, 95% CI 1.10 to 1.59, one trial (USA), 615 participants, low quality evidence; TB treatment completion: 100% versus 88%; RR 1.14, 95% CI 1.02 to 1.27, one trial (Thailand), 92 participants, low quality evidence). Clinic attendance and TB treatment completion were also higher with default reminders (letters or home visits) (clinic attendance: 52% versus 10%; RR 5.04, 95% CI 1.61 to 15.78, one trial (India), 52 participants, low quality evidence; treatment completion: RR 1.17, 95% CI 1.11 to 1.24, two trials (Iraq and India), 680 participants, moderate quality evidence). For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls (63% versus 48%; RR 1.30, 95% CI 1.07 to 1.59, one trial (USA), 536 participants); and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits (93% versus 65%, one trial (Spain), 318 participants). For people undergoing screening for TB, three trials of pre-appointment phone-calls found little or no effect on the proportion of people returning to clinic for the result of their skin test (three trials, 1189 participants, low quality evidence), and two trials found little or no effect with take home reminder cards (two trials, 711 participants). All four trials were conducted among healthy volunteers in the USA. Authors' conclusions Policies of sending reminders to people pre-appointment, and contacting people who miss appointments, seem sensible additions to any TB programme, and the limited evidence available suggests they have small but potentially important benefits. Future studies of modern technologies such as short message service (SMS) reminders would be useful, particularly in low-resource settings. Plain Language Summary Reminder systems to improve patient attendance at tuberculosis clinics This Cochrane Review summarizes trials evaluating the effects of reminder systems on attendance at tuberculosis (TB) clinics and completion of TB treatment. After searching for relevant trials up to 29 August 2014, we included nine trials, including 4654 people. What are reminder systems and how might they help? Effective treatment for TB requires people to take multiple drugs daily for at least six months. Consequently, once they start to feel well again, some patients stop attending clinics and stop taking theirmedication which can lead to the illness returning and the development of drug resistance. One strategy theWorldHealthOrganization recommends is that an appointed person (a health worker or volunteer) watches the person take their medication everyday (called direct observation). Other strategies include reminder systems to prompt patients to attend for appointments on time, or to re-engage people who have missed or defaulted on a scheduled appointment. These prompts may be in the form of telephone calls or letters before the next scheduled appointment (“pre-appointment reminders”), or phone calls, letters, or home visits after a missed appointment (“default reminders”). What the research says: For people being treated for active TB: - More people attended the clinic and completed TB treatment with pre-appointment reminder phone-calls (low quality evidence). - More people attended the clinic and completed TB treatment with a policy of default reminders (low and moderate quality evidence respectively). For people on TB prophylaxis: - More people attended the clinic with pre-appointment phone-calls, and the number attending the final clinic was higher with threemonthly phone-calls or nurse home visits. For people being treated for active TB: - Similar numbers of people attended clinic for skin test reading with and without pre-appointment phone-calls (low quality evidence). - Similar numbers of people attended clinic for skin test reading with and without take home reminder cards.

Background Reminder systems and late patient tracers as strategies to improve patients' adherence to tuberculosis screening, diagnosis, and treatment are used in some countries, but their effectiveness has not previously been systematically reviewed. Objectives To assess the effects of reminder systems and late patient tracers on completion of diagnostics, commencement of treatment in people referred for curative or prophylactic treatment of tuberculosis, completion of treatment in people starting curative or prophylactic treatment for tuberculosis, and cure in people being treated for active tuberculosis. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register ( June 2008), Cochrane Effective Practice and Organization of Care Group Specialized Register ( April 2007), CENTRAL ( The Cochrane Library 2008, Issue 2), MEDLINE ( 1966 to June 2008), EMBASE ( 1974 to June 2008), LILACS ( 1982 to June 2008), CINAHL ( 1982 to June 2008), SCI-EXPANDED ( 1945 to June 2008), SSCI ( 1956 to June 2008), mRCT ( June 2008), Indian Journal of Tuberculosis ( 1983 to June 2008), and reference lists. We also contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing any reminders or late patient tracers with no or other kinds of reminders or late patient tracers. We included people in any setting who require treatment for tuberculosis or require prophylaxis against tuberculosis and are referred to tuberculosis diagnostic or screening services. Data collection and analysis Two authors independently assessed trial risk of bias and extracted data. Nometa-analysis could be undertaken due to the heterogeneity of interventions across trials. Main results Nine trials involving 5257 participants met the inclusion criteria. Three assessed the use of late patient tracers, and six assessed reminder systems. Late patient tracers ( home visit and letter) were shown to be beneficial in increasing adherence to tuberculosis treatment compared with no late patient tracer. The results from almost all the reminder trials, except one, show benefits of different types of reminders compared to no reminder on adherence to tuberculosis clinic appointments. Authors' conclusions The included trials show significantly better outcomes among those tuberculosis patients for which late patient tracers and reminders are used. Studies of good quality ( large and with rigorous study design) are needed to decide the most effective late patient tracer actions and reminders in different settings. Future studies of reminders in chemoprophylaxis and treatment settings would be useful.

Multidrug-resistant tuberculosis (MDR-TB) is on the increase with several Eastern European countries having a prevalence of more than ten percent. This resistance means that patients may not be cured with standard regimens even if they adhere well to treatment. An MDR-TB programme requires advanced medical care infection control measures counselling and good follow-up as one centre in the Philippines reports in a study published in PLoS Medicine. The DOTS-Plus (directly observed treatment short-course) project is run by the Makati Medical Center supported by the Tropical Disease Foundation. The Center has exceptional management capacity and was one of the first few nongovernmental organizations to be a principal recipient of grants from the Global Fund to Fight AIDS Tuberculosis and Malaria (known as the Global Fund). The Center itself provides high-quality tertiary care. Within this setting clinicians from the Makati Medical Center used drug history and sensitivity testing to provide individualised regimens of expensive second-line drugs estimated to cost more than US$1500 per patient. The authors report on a cohort of 171 patients with MDR-TB of whom 117 were enrolled and analysed with 61 percent cured. Indirect outcome data from patients from other countries were then combined with local cost data to estimate the number of premature deaths and secondary cases averted in order to provide an estimate of the mean cost per disability-adjusted life year gained. (excerpt)