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1. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

Axfors, C., Janiaud, P., Schmitt, A. M., van't Hooft, J., Smith, E. R., Haber, N. A., Abayomi, A., Abduljalil, M., Abdulrahman, A., Acosta-Ampudia, Y., Aguilar-Guisado, M., Al-Beidh, F., Alejandria, M. M., Alfonso, R. N., Ali, M., Alqahtani, M., Alzamrooni, A., Anaya, J. -M., Ang, M. A. C., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., Kjeldsen-Kragh, J., Klenerman, P., Kotecha, A., Krapp, F., Labanca, L., Laing, E., Landin-Olsson, M., Laterre, P. -F., Lim, L. -L., Lim, J., Ljungquist, O., Llaca-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), Teofili L. (ORCID:0000-0002-7214-1561), Axfors, C., Janiaud, P., Schmitt, A. M., van't Hooft, J., Smith, E. R., Haber, N. A., Abayomi, A., Abduljalil, M., Abdulrahman, A., Acosta-Ampudia, Y., Aguilar-Guisado, M., Al-Beidh, F., Alejandria, M. M., Alfonso, R. N., Ali, M., Alqahtani, M., Alzamrooni, A., Anaya, J. -M., Ang, M. A. C., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., Kjeldsen-Kragh, J., Klenerman, P., Kotecha, A., Krapp, F., Labanca, L., Laing, E., Landin-Olsson, M., Laterre, P. -F., Lim, L. -L., Lim, J., Ljungquist, O., Llaca-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), and Teofili L. (ORCID:0000-0002-7214-1561)

Abstract

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

Published
2021

5. Reminder systems and late patient tracers in the diagnosis and management of tuberculosis

Author

Liu, Q., Abba, Katharine, Alejandria, M. M., Balanag, V. M., Berba, R. P., and Lansang, M. A. D.

Subjects
education, wf_220, wf_200, wf_310
Abstract

Background\ud 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.\ud Objectives\ud 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.\ud Search strategy\ud 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.\ud Selection criteria\ud 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.\ud Data collection and analysis\ud Two authors independently assessed trial risk of bias and extracted data. Nometa-analysis could be undertaken due to the heterogeneity of interventions across trials.\ud Main results\ud 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.\ud Authors' conclusions\ud 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.

Published
2008

9. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results

Author

Carlos Guijarro, Farid Zand, Mohamed solyman Kabil, Sven Trelle, Birgitte Tholin, Belén Comeche, Johan Alexander Azañero Haro, Gonzalo Sierra Torres, Quarraisha Abdool Karim, Kari Tikkinen, Jean-michel Molina, Atousa Hakamifard, George M Varghese, Oscar Josue Ponce Ponte, Mazin Barry, Pilar Vizcarra, Niccolo Riccardi, Natalia Pérez-Macias, Aynaa AlSharidi, Nelson Lee, Alexandra Binnie, Firouzé BANI-SADR, Beatriz Díaz-Pollán, Aldo Pietro Maggioni, Ilkka Kalliala, Florian Desgranges, Anders Benjamin Kildal, Katerina Nezvalova-Henriksen, Corinne Merle, Andrés Martín Alcántara, Benjamin Gaborit, Daniel Lozano Martín, Antonio Ramos-Martinez, Miguel Villegas-Chiroque, Fredy Orlando Guevara Pulido, Ana Fernández-Cruz, Cormac McCarthy, Thesla Palanee-Phillips, Annalisa Marinosci, Abdullah Assiri, Florent Wallet, Juan Pablo Balbuena, Avik Ray, Francesc Puchades, Rajarao Mesipogu, Marjatta Sinisalo, Jonathan Sterne, Antonio Portolés, Heike Cappel-Porter, Jussi Mustonen, Jeremy Nel, BRUNO MOURVILLIER, María Consuelo Miranda Montoya, Chiara Fanciulli, L Marjukka Myllärniemi, Edinson Dante Meregildo Rodriguez, Alexy Inciarte, Mohamed Hassany, François Danion, Elena Muñez Rubio, Jean-Pierre QUENOT, Esperanza Merino de Lucas, Sheela Godbole, Luis Guillermo Barreto Rocchetti, Katerina Spasovska, William Connors, Kiana Shirani, Umang Agrawal, Srinivas Murthy, Bjorn Blomberg, Vasee Moorthy, Amith Balachandran, Antonio De Pablo Esteban, Mahnaz Amini, Dag Arne Lihaug Hoff, Zeinab Siami, Guillaume Martin-Blondel, Heng Gee Lee, Thrilok Chander Bingi, Vijay Krishnan, ANA BELEN RIVAS PATERNA, Eric D'Ortenzio, Samy Zaky, Carlos Arturo Alvarez-Moreno, Alonso Soto, VIKAS MARWAH, Marco Tulio Medina, Zaira R. Palacios-Baena, Jean-Sébastien Hulot, Miguel Angel Hueda Zavaleta, Felipe García, Francisco Fanjul, Hospices Civils de Lyon (HCL), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, Université Paris Diderot - Paris 7 (UPD7), Michel-Avella, Amandine, Pan, H., Peto, R., Henao-Restrepo, A. -M., Preziosi, M. -P., Sathiyamoorthy, V., Karim, Q. A., Alejandria, M. M., Garcia, C. H., Kieny, M. -P., Malekzadeh, R., Murthy, S., Srinath Reddy, K., Periago, M. R., Hanna, P. A., Ader, F., Al-Bader, A. M., Alhasawi, A., Allum, E., Alotaibi, A., Alvarez-Moreno, C. A., Appadoo, S., Asiri, A., Aukrust, P., Barratt-Due, A., Bellani, S., Branca, M., Cappel-Porter, H. B. C., Cerrato, N., Chow, T. S., Como, N., Eustace, J., Garcia, P. J., Godbole, S., Gotuzzo, E., Griskevicius, L., Hamra, R., Hassan, M., Hassany, M., Hutton, D., Irmansyah, I., Jancoriene, L., Kirwan, J., Kumar, S., Lennon, P., Lopardo, G., Lydon, P., Magrini, N., Maguire, T., Manevska, S., Manuel, O., Mcginty, S., Medina, M. T., Mesa Rubio, M. L., Miranda-Montoya, M. C., Nel, J., Nunes, E. P., Perola, M., Portoles, A., Rasmin, M. R., Raza, A., Rees, H., Reges, P. P. S., Rogers, C. A., Salami, K., Salvadori, M. I., Sinani, N., Sterne, J. A. C., Stevanovikj, M., Tacconelli, E., Tikkinen, K. A. O., Trelle, S., Zaid, H., Rottingen, J. -A., Swaminathan S., &amp, Luzzati, R, Di Bella, S, Doctoral Programme in Population Health, Doctoral Programme in Biomedicine, HUS Abdominal Center, Department of Surgery, Urologian yksikkö, South Carelia Social and Health care District Eksote, HUS Heart and Lung Center, Department of Medicine, Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale

Subjects
Male, Kaplan Meier method, Intention to Treat Analysi, MESH: Treatment Failure, MESH: Hydroxychloroquine, remdesivir, Rate ratio, MESH: Intention to Treat Analysis, MESH: Length of Stay, law.invention, Lopinavir/*therapeutic use, 0302 clinical medicine, middle aged, Medicine, Hospital Mortality, MESH: Respiration, Artificial, Antiviral Agents/administration & dosage/adverse effects/*therapeutic use, comparative study, beta1a interferon, MESH: Middle Aged, Alanine, Respiration, adult, clinical trial, General Medicine, 3. Good health, Intention to Treat Analysis, [SDV] Life Sciences [q-bio], aged, health care quality, priority journal, drug withdrawal, Artificial, Interferon, Drug Therapy, Combination, medicine.medical_specialty, Initiation of ventilation, Interferon beta-1a/*therapeutic use, World Health Organization, Antiviral Agents, Article, Duration of hospital stay, antiviral drugs, 03 medical and health sciences, Drug Therapy, death, Humans, MESH: Hospital Mortality, human, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, treatment duration, extracorporeal oxygenation, Hydroxychloroquine, Length of Stay, major clinical study, mortality, Respiration, Artificial, Adenosine Monophosphate/*analogs & derivatives/therapeutic use, multicenter study, Alanine/*analogs & derivatives/therapeutic use, MESH: Interferon beta-1a, randomized controlled trial, MESH: Female, antivirus agent, [SDV]Life Sciences [q-bio], MESH: Hospitalization, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Lopinavir, Adenosine Monophosphate, COVID-19, Female, Hospitalization, Interferon beta-1a, Middle Aged, Treatment Failure, Randomized controlled trial, Interquartile range, law, MESH: COVID-19, MESH: Adenosine Monophosphate, 030212 general & internal medicine, antiviral drugs, Covid-19, MESH: Aged, Hydroxychloroquine/*therapeutic use, MESH: Lopinavir, Covid19, artificial ventilation, drug therapy, ritonavir, hospital patient, female, Combination, medicine.drug, MESH: Antiviral Agents, combination drug therapy, COVID-19/*drug therapy/mortality, Randomization, MESH: Alanine, drug repositioning, drug clearance, adenosine phosphate, coronavirus disease 2019, length of stay, Internal medicine, controlled study, Antiviral Agent, Intention-to-treat analysis, business.industry, MESH: Male, COVID-19 Drug Treatment, purl.org/pe-repo/ocde/ford#3.02.00 [https], MESH: Drug Therapy, Combination, 3121 General medicine, internal medicine and other clinical medicine, business
Abstract

The authors report interim results of the WHO Solidarity trial of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with Covid-19. Effects on overall mortality, initiation of ventilation, and duration of hospital stay are compared. Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ; ClinicalTrials.gov number, .)

Published
2020
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11. HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline.

Author

Salvaña EMT, Dungca NT, Arevalo G, Li K, Francisco C, Penalosa C, Dela Tonga A, Leyritana K, Solante R, Tactacan-Abrenica RJ, Lim J, Alejandria M, Palaypayon N, and Schwem B

Subjects
Drug Resistance, Drug Resistance, Viral genetics, Genotype, Humans, Philippines epidemiology, Viral Load, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 genetics
Abstract

Objectives: The Philippines has one of the fastest growing HIV epidemics in the world. A subtype shift from B to CRF01&#95;AE may have contributed to the increase in cases. We undertook a genotyping and transmitted drug resistance (TDR) study to determine if the dominant subtype has any advantages in resistance and transmission., Methods: Filipinos who were treatment-naive who were living with HIV were recruited from two large government treatment hubs from March 2016 to August 2018. HIV-1 viral load, CD4 count, genotyping, and TDR testing were performed. Demographic and clinical data were collected and compared across subtypes., Results: A total of 298 Filipinos living with HIV were recruited. Median CD4 count was 143 cells/µl and HIV viral load was 2,345,431 copies/ml. Sanger-based sequencing showed 230/298 (77.2%) had subtype CRF01&#95;AE, 41 (13.8%) subtype B, and the rest had other subtypes or recombinants. Overall TDR was 11.7%. TDR was associated with lower viral loads and no previous HIV testing. CRF01&#95;AE had a higher likelihood of a viral load >100,000 copies/ml and having a baseline CD4 count <50 cells/mm 3 ., Conclusion: TDR in the Philippines is high at 11.7%. CRF01&#95;AE was observed to have a higher baseline viral load and lower CD4 counts compared with other cocirculating subtypes. Further research needs to confirm this observation because it suggests that CRF01&#95;AE may have a survival advantage that led to replacement of subtype B as the dominant subtype. Drug resistance testing is recommended in the Philippines when initiating NNRTI-based antiretroviral therapy but may not be necessary for INSTI-based regimens., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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12. Metabolic Profile of People Living with HIV in a Treatment Hub in Manila, Philippines: A Pre- and Post-Antiretroviral Analysis.

Author

Francisco C, Gonzales E, Yu MG, Salvaña EM, Abad C, Reganit PF, Maningat P, Sison O, and Alejandria M

Subjects
Male, Humans, Adult, Female, Philippines, Anti-Retroviral Agents therapeutic use, Metabolome, HIV Infections drug therapy, Dyslipidemias
Abstract

Objectives: People living with HIV (PLHIV) are susceptible to develop dyslipidemia and hyperglycemia. This study aims to determine the prevalence of these metabolic derangements among Filipino PLHIV., Methodology: We reviewed 635 medical records in a treatment hub in Manila, Philippines from January 2004 to July 2016. Logistic regression analysis was done to determine factors associated with dyslipidemia and hyperglycemia pre- and post-ART., Results: Among 635 PLHIV, 97.3% were males with mean age of 30 years and median CD4 count of 207 cells/mm 3 . Pre-ART, prevalence of dyslipidemia was 65.4% and hyperglycemia was 10.4%. Risk factors for dyslipidemia include hyperglycemia (AOR 3.8, p 0.001) and >320 days delay in ART initiation from HIV confirmation (AOR 1.5, p 0.032), while dyslipidemia was associated with hyperglycemia (AOR 3.1, p 0.001). Post-ART, prevalence of dyslipidemia was 48.6% and hyperglycemia was 15.6%. Risk factors for post-ART dyslipidemia include being WHO stage 4 (AOR 2.1, p 0.021), hyperglycemia (AOR 16.1, p <0.001), >36 months ART duration (AOR 8.7, p <0.001) and efavirenz-based ART (AOR 2.8, p <0.001). Low CD4 count post-ART had a negative correlation with dyslipidemia (AOR 0.5, p 0.005). Post-ART hyperglycemia was associated with age >30 years (AOR 2.1, p 0.004), being overweight (AOR 1.8, p 0.023), dyslipidemia (AOR 17.8, p <0.001) and zidovudine-based ART (AOR 1.4, p 0.051)., Conclusion: Dyslipidemia and hyperglycemia prevalence was high in Filipino PLHIV. Traditional, HIV and treatment related factors contributed to its development. Intensive monitoring and initiation of appropriate treatment is recommended., Competing Interests: All authors certified fulfillment of ICMJE authorship criteria., (© 2022 Journal of the ASEAN Federation of Endocrine Societies.)

Published
2022
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13. Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines.

Author

Tablizo FA, Saloma CP, Castro MJR, Kim KM, Yangzon MSL, Lapid CM, Maralit BA, Ayes MEC, Yap JMC, Llames JS, Araiza SMM, Punayan KP, Asin ICA, Tambaoan CFB, Chong ALU, Padilla KSAR, Cruz RPS, Morado EKD, Dizon JGA, Cutiongco-de la Paz EM, de Guzman AR, Hao RNM, Zamora AA, Pacial DR, Magalang JAR, Alejandria M, Carlos C, Ong-Lim A, Salvaña EM, Wong JQ, Montoya JC, and Singh-Vergeire MR

Abstract

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., (Copyright © 2021 Tablizo et al.)

Published
2021
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14. High rates of tenofovir failure in a CRF01&#95;AE-predominant HIV epidemic in the Philippines.

Author

Salvana EMT, Samonte GMJ, Telan E, Leyritana K, Tactacan-Abrenica RJ, Ching PR, Arevalo GM, Dungca NT, Peñalosa-Ramos C, Mendoza KAR, Trinidad LF, Tonga AD, Lim J, Destura R, Alejandria M, Solante R, Arcangel L, Palaypayon NS, and Schwem BE

Subjects
Adult, Drug Resistance, Viral genetics, Drug Therapy, Combination, Epidemics, Female, HIV genetics, HIV Infections epidemiology, HIV Infections virology, Humans, Male, Philippines epidemiology, Treatment Failure, Viral Load, Zidovudine therapeutic use, Anti-HIV Agents therapeutic use, HIV classification, HIV Infections drug therapy, Tenofovir therapeutic use
Abstract

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&#95;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&#95;AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58-7.52 p < 0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature., Conclusions: HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01&#95;AE-predominant epidemics., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2020
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15. Primary intracranial leiomyosarcoma among patients with AIDS in the era of new chemotherapeutic and biological agents.

Author

Francisco CN, Alejandria M, Salvaña EM, and Andal VMV

Subjects
Adult, Biopsy, Brain Neoplasms complications, Brain Neoplasms diagnostic imaging, Brain Neoplasms therapy, Chemotherapy, Adjuvant, Combined Modality Therapy, HIV Infections complications, Headache etiology, Humans, Leiomyosarcoma complications, Leiomyosarcoma diagnostic imaging, Leiomyosarcoma therapy, Magnetic Resonance Imaging, Male, Radiotherapy, Adjuvant, Tomography, X-Ray Computed, Brain Neoplasms pathology, Leiomyosarcoma pathology
Abstract

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2018
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16. Regional Differences in the Prevalence of Major Opportunistic Infections among Antiretroviral-Naïve Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines.

Author

Gangcuangco LMA, Sawada I, Tsuchiya N, Do CD, Pham TTT, Rojanawiwat A, Alejandria M, Leyritana K, Yokomaku Y, Pathipvanich P, and Ariyoshi K

Subjects
AIDS-Related Opportunistic Infections complications, Adult, Cohort Studies, Female, Geography, HIV Infections complications, Humans, Japan epidemiology, Male, Middle Aged, Odds Ratio, Philippines epidemiology, Prevalence, Thailand epidemiology, Vietnam epidemiology, AIDS-Related Opportunistic Infections epidemiology, Cryptococcosis epidemiology, Cytomegalovirus Infections epidemiology, HIV Infections epidemiology, Pneumonia, Pneumocystis epidemiology, Tuberculosis epidemiology
Abstract

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)-naïve 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-naïve patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted.

Published
2017
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18. A cost-utility analysis of cervical cancer screening and human papillomavirus vaccination in the Philippines.

Author

Guerrero AM, Genuino AJ, Santillan M, Praditsitthikorn N, Chantarastapornchit V, Teerawattananon Y, Alejandria M, and Toral JA

Subjects
Adolescent, Adult, Cost-Benefit Analysis, Early Detection of Cancer economics, Female, Humans, Managed Care Programs economics, Middle Aged, Papanicolaou Test economics, Papillomavirus Vaccines administration & dosage, Philippines ethnology, Vaccination statistics & numerical data, Papillomavirus Infections economics, Papillomavirus Infections prevention & control, Papillomavirus Vaccines economics, Uterine Cervical Neoplasms economics, Uterine Cervical Neoplasms prevention & control, Vaccination economics
Abstract

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.

Published
2015
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19. Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines.

Author

Haasis MA, Ceria JA, Kulpeng W, Teerawattananon Y, and Alejandria M

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Female, Financing, Government, Humans, Income, Infant, Infant, Newborn, Male, Markov Chains, Middle Aged, Philippines, Pneumococcal Vaccines administration & dosage, Pneumonia, Pneumococcal immunology, Pneumonia, Pneumococcal microbiology, Streptococcus pneumoniae drug effects, Streptococcus pneumoniae immunology, Vaccines, Conjugate, Cost-Benefit Analysis, Immunization Programs economics, Pneumococcal Vaccines economics, Pneumonia, Pneumococcal prevention & control, Vaccination economics
Abstract

Objectives: The 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., Methods: A 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., Results: With 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., Conclusion: The 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.

Published
2015
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20. Prevalence and risk factors for trimethoprim-sulfamethoxazole-resistant Escherichia coli among women with acute uncomplicated urinary tract infection in a developing country.

Author

Gangcuangco LM, Alejandria M, Henson KE, Alfaraz L, Ata RM, Lopez M, and Saniel M

Subjects
Acute Disease, Adult, Anti-Bacterial Agents therapeutic use, Developing Countries, Escherichia coli Infections drug therapy, Escherichia coli Infections epidemiology, Female, Fluoroquinolones pharmacology, Fluoroquinolones therapeutic use, Humans, Microbial Sensitivity Tests, Prevalence, Prospective Studies, Risk Factors, Staphylococcal Infections epidemiology, Staphylococcus saprophyticus drug effects, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use, Urinary Tract Infections drug therapy, Urinary Tract Infections epidemiology, Young Adult, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Escherichia coli Infections microbiology, Trimethoprim, Sulfamethoxazole Drug Combination pharmacology, Urinary Tract Infections microbiology, Uropathogenic Escherichia coli drug effects
Abstract

Background: Prospective studies from developing countries that have investigated risk factors for trimethoprim-sulfamethoxazole (TMP-SMX)-resistant Escherichia coli in women with uncomplicated urinary tract infection (UTI) remain scarce., Methods: Women with acute uncomplicated UTI were enrolled prospectively. Urine was sent for antimicrobial susceptibility testing. Logistic regression analysis was used to identify risk factors for TMP-SMX resistance., Results: Of 405 participants, 229 (56.5%) had bacteriuria (mean age 31.9 ± 9.5 years). In the previous 12 months, 77 (33.6%) had experienced at least one UTI episode and 106 (46.3%) reported antimicrobial use. The most common uropathogens were E. coli (75.8%) and Staphylococcus saprophyticus (8.9%). For the 179 E. coli, resistance rates were highest for ampicillin (64.3%) and TMP-SMX (41.3%). Resistance to cephalosporins, nitrofurantoin, and fluoroquinolones was much lower compared with the hospital laboratory-based surveillance data. Risk factors for TMP-SMX resistance were UTI in the last 6 months (odds ratio 2.22; p = 0.04) and the number of UTI episodes in the past year (odds ratio 2.06; p = 0.004). The number of UTI episodes (adjusted odds ratio 2.21; p = 0.02) remained significant on multivariate analysis., Conclusions: TMP-SMX resistance was high. Number of previous UTI episodes was associated with increased risk of resistance; prior antimicrobial use was not. Hospital antibiograms should be used with caution when treating uncomplicated UTI., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2015
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21. Is DOTS-plus a feasible and cost-effective strategy?

Author

Garner P, Alejandria M, and Lansang MA

Subjects
Cost-Benefit Analysis, Feasibility Studies, Humans, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant therapy, World Health Organization, Directly Observed Therapy economics, Tuberculosis, Multidrug-Resistant economics
Published
2006
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22. Dengue fever.

Author

Alejandria M

Subjects
Adrenal Cortex Hormones therapeutic use, Adrenochrome analogs & derivatives, Adrenochrome therapeutic use, Child, Fluid Therapy, Humans, Immunoglobulins therapeutic use, Infusions, Intravenous, Dengue therapy
Published
2005

23. An Asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia.

Author

Ngeow YF, Suwanjutha S, Chantarojanasriri T, Wang F, Saniel M, Alejandria M, Hsueh PR, Ping-Ing L, Park SC, Sohn JW, Aziah AM, Liu Y, Seto WH, Ngan CC, Hadiarto M, Hood A, and Cheong YM

Subjects
Adolescent, Adult, Agglutination Tests, Child, Child, Preschool, Chlamydophila pneumoniae genetics, Community-Acquired Infections diagnosis, DNA, Bacterial chemistry, DNA, Bacterial genetics, Asia, Eastern epidemiology, Female, Fluorescent Antibody Technique, Indirect, Humans, Male, Middle Aged, Mycoplasma pneumoniae genetics, Pneumonia, Bacterial diagnosis, Polymerase Chain Reaction, Prevalence, Chlamydophila pneumoniae isolation & purification, Community-Acquired Infections epidemiology, Community-Acquired Infections microbiology, Legionella pneumophila isolation & purification, Mycoplasma pneumoniae isolation & purification, Pneumonia, Bacterial epidemiology, Pneumonia, Bacterial microbiology
Abstract

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.

Published
2005
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24. Dengue fever.

Author

Alejandria M

Subjects
Adult, Child, Fluid Therapy, Humans, Immunoglobulins, Intravenous therapeutic use, Infusions, Intravenous, Dengue therapy
Published
2004

25. Detection of antibodies against spotted fever group Rickettsia (SFGR), typhus group Rickettsia (TGR), and Coxiella burnetii in human febrile patients in the Philippines.

Author

Camer GA, Alejandria M, Amor M, Satoh H, Muramatsu Y, Ueno H, and Morita C

Subjects
Coxiella burnetii immunology, Coxiella burnetii isolation & purification, Female, Fever epidemiology, Fluorescent Antibody Technique, Indirect, Humans, Male, Philippines epidemiology, Rickettsia classification, Rickettsia genetics, Rickettsia immunology, Seroepidemiologic Studies, Typhus, Epidemic Louse-Borne immunology, Antibodies, Bacterial blood, Q Fever epidemiology, Rickettsia isolation & purification, Rickettsia Infections epidemiology, Typhus, Epidemic Louse-Borne epidemiology
Abstract

A total of 157 sera from febrile patients in the Philippine General Hospital in Manila, Luzon, and the Northern Samar Provincial Hospital, the Philippines, were used. Serum antibodies against spotted fever group Rickettsia (SFGR) and typhus group Rickettsia (TGR) were detected by indirect immunofluorescence test. Antibody positive rates were 1.3% for SFGR (Rickettsia japonica) and 2.5% for TGR (R. typhus), respectively. Rickettsial antibodies in humans in the Philippines were found for the first time. These results underscore the need for further epidemiological study of clinical rickettsioses in the Philippines.

Published
2003

26. Intravenous immunoglobulin for treating sepsis and septic shock.

Author

Alejandria MM, Lansang MA, Dans LF, and Mantaring JB

Subjects
Humans, Randomized Controlled Trials as Topic, Sepsis mortality, Shock, Septic mortality, Immunoglobulins, Intravenous therapeutic use, Sepsis drug therapy, Shock, Septic drug therapy
Abstract

Background: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality., Objectives: To estimate the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital., Search Strategy: We searched the Cochrane Infectious Diseases Group specialized register up to November 2001; the Cochrane Controlled Trials Register, The Cochrane Library issue 4, 2001; MEDLINE 1966 to November 2001; and EMBASE 1988 to September 2001. We contacted investigators active in the field for unpublished data., Selection Criteria: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock., Data Collection and Analysis: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation., Main Results: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95%CI 0.86-0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). For the two high-quality trials on polyclonal IVIG, the RR for overall mortality was 0.30, but the confidence interval was wide (95% CI 0.09 to 0.99, n=91). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69)., Reviewer's Conclusions: Polyclonal IVIG significantly reduced mortality and and is a promising adjuvant in the treatment of sepsis and septic shock. However, all the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

Published
2002
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