Displaying publications 1 - 20 of 21 in total

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  1. Nejat N, Vadamalai G, Davis RE, Harrison NA, Sijam K, Dickinson M, et al.
    Int. J. Syst. Evol. Microbiol., 2013 Feb;63(Pt 2):540-8.
    PMID: 22523165 DOI: 10.1099/ijs.0.041467-0
    This study addressed the taxonomic position and group classification of a phytoplasma responsible for virescence and phyllody symptoms in naturally diseased Madagascar periwinkle plants in western Malaysia. Unique regions in the 16S rRNA gene from the Malaysian periwinkle virescence (MaPV) phytoplasma distinguished the phytoplasma from all previously described 'Candidatus Phytoplasma' species. Pairwise sequence similarity scores, calculated through alignment of full-length 16S rRNA gene sequences, revealed that the MaPV phytoplasma 16S rRNA gene shared 96.5 % or less sequence similarity with that of previously described 'Ca. Phytoplasma' species, justifying the recognition of the MaPV phytoplasma as a reference strain of a novel taxon, 'Candidatus Phytoplasma malaysianum'. The 16S rRNA gene F2nR2 fragment from the MaPV phytoplasma exhibited a distinct restriction fragment length polymorphism (RFLP) profile and the pattern similarity coefficient values were lower than 0.85 with representative phytoplasmas classified in any of the 31 previously delineated 16Sr groups; therefore, the MaPV phytoplasma was designated a member of a new 16Sr group, 16SrXXXII. Phytoplasmas affiliated with this novel taxon and the new group included diverse strains infecting periwinkle, coconut palm and oil palm in Malaysia. Three phytoplasmas were characterized as representatives of three distinct subgroups, 16SrXXXII-A, 16SrXXXII-B and 16SrXXXII-C, respectively.
  2. Lu J, Li Y, Hu D, Chen X, Liu Y, Wang L, et al.
    Saudi J Biol Sci, 2016 Jan;23(1):S22-31.
    PMID: 26858562 DOI: 10.1016/j.sjbs.2015.06.012
    A novel interpenetrating network hydrogel for drug controlled release, composed of modified poly(aspartic acid) (KPAsp) and carboxymethyl chitosan (CMCTS), was prepared in aqueous system. The surface morphology and composition of hydrogels were characterized by SEM and FTIR. The swelling properties of KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated and the swelling dynamics of the hydrogels was analyzed based on the Fickian equation. The pH, temperature and salt sensitivities of hydrogels were further studied, and the prepared hydrogels showed extremely sensitive properties to pH, temperature, the ionic salts kinds and concentration. The results of controlled drug release behaviors of the hydrogels revealed that the introduction of IPN observably improved the drug release properties of hydrogels, the release rate of drug from hydrogels can be controlled by the structure of the hydrogels and pH value of the external environment, a relative large amount of drug released was preferred under simulated intestinal fluid. These results illustrated high potential of the KPAsp/CMCTS IPN hydrogels for application as drug carriers.
  3. Wu T, Wang X, Zhang Z, Gong F, Song T, Chen Z, et al.
    J Bioinform Comput Biol, 2016 06;14(3):1650013.
    PMID: 27225342 DOI: 10.1142/S021972001650013X
    A nuclear export signal (NES) is a protein localization signal, which is involved in binding of cargo proteins to nuclear export receptor, thus contributes to regulate localization of cellular proteins. Consensus sequences of NES have been used to detect NES from protein sequences, but suffer from poor predictive power. Some recent peering works were proposed to use biochemical properties of experimental verified NES to refine NES candidates. Those methods can achieve high prediction rates, but their execution time will become unacceptable for large-scale NES searching if too much properties are involved. In this work, we developed a novel computational approach, named NES-REBS, to search NES from protein sequences, where biochemical properties of experimental verified NES, including secondary structure and surface accessibility, are utilized to refine NES candidates obtained by matching popular consensus sequences. We test our method by searching 262 experimental verified NES from 221 NES-containing protein sequences. It is obtained that NES-REBS runs in 2-3[Formula: see text]mins and performs well by achieving precision rate 47.2% and sensitivity 54.6%.
  4. Cao N, Zhao A, Zhao G, Wang X, Han B, Lin R, et al.
    Integr Cancer Ther, 2015 Mar;14(2):133-9.
    PMID: 25567328 DOI: 10.1177/1534735414564185
    BACKGROUND: In China, traditional Chinese herbal medicine (TCHM) has been widely used for pancreatic cancer. This retrospective, matched case-control study aimed to assess factors affecting the survival time of patients with pancreatic cancer.
    METHODS: From 2004 to 2012, a total of 411 patients with pathologically confirmed pancreatic cancer were enrolled, and 272 patients were matched and divided into TCHM and non-TCHM groups (control group) based on received TCHM or not. The match was according to gender, age of onset, radiotherapy, and chemotherapy. Both groups received comprehensive treatments, the TCHM group simultaneously received the TCHM spleen-invigorating compound for more than 3 months. The Cox model was used for prognostic factor analysis and the Kaplan-Meier method for estimating median overall survival (OS) and disease-free survival (DFS).
    RESULTS: In 130 patients with advanced pancreatic cancer, COX analysis showed the Karnofsky Performance Scale (KPS; P = .000), radiotherapy (P = .003), and TCHM (P = .001) were independent prognostic factors for OS, with median OS of 12.7 and 9.9 months in TCHM and non-TCHM groups, respectively (hazard ratio [HR] = 0.520; 95% confidence interval [CI] = 0.353-0.766; P = .033). In 142 patients undergoing radical surgery, KPS (P = .000) and TCHM (P = .000) were independent prognostic factors for OS and DFS, median OS was 23.8 and 12.4 months in TCHM and non-TCHM groups, respectively (HR = 0.373; 95% CI = 0.251-0.554; P = .000), and the median DFS was 21.5 and 10.2 months in TCHM and non-TCHM groups, respectively (HR = 0.352; 95% CI = 0.237-0.522; P = .000).
    CONCLUSIONS: KPS was an important prognostic factor of pancreatic cancer. Spleen-invigorating compounds could have an effect on improving the prognosis of pancreatic cancer patients.
  5. Luo N, Tan LC, Zhao Y, Lau PN, Au WL, Li SC
    Mov. Disord., 2009 Jan 30;24(2):183-7.
    PMID: 18972545 DOI: 10.1002/mds.22240
    The aim of our study was to assess the longitudinal validity of the 8-item Parkinson's Disease Questionnaire (PDQ-8) in terms of responsiveness and test-retest reliability and to determine the minimally important difference (MID) for PDQ-8 using the anchor-based approach in Asians with Parkinson's disease (PD). A consecutive sample of PD patients attending a tertiary neuroscience clinic in Singapore completed the English or Chinese version of PDQ-8 twice during two different clinic visits. During the second visit, patients were also asked to rate their changes in health in general, PD severity, and overall impact of PD since at the time of their first visit 1 year ago using a 5-point response scale. A total of 96 patients participated in the study. For patients who reported changed conditions in the second visit, responsiveness measured by Cohen's effect size, standardized response mean, and Guyatt's responsiveness index ranged from 0.21 to 0.68. The intraclass correlation coefficient values calculated using patients reporting no change in health or PD status ranged from 0.64 to 0.76. The mean changed PDQ-8 summary index score in patients who reported that their health or PD status worsened only "a little bit" ranged from 5.8 to 7.4 points. Our current results show that PDQ-8 is a longitudinally reliable and responsive measure for assessing the health-related quality of life in patients with PD. The MID of the PDQ-8 estimated in the study will further support the use of this instrument in both clinical research and practice.
  6. Wang Y, Zhao Y, Xu L, Wang W, Doherty L, Tang C, et al.
    Water Sci. Technol., 2017 Jul;76(2):471-477.
    PMID: 28726712 DOI: 10.2166/wst.2017.190
    In the last 10 years, the microbial fuel cell (MFC) has been extensively studied worldwide to extract energy from wastewater via electricity generation. More recently, a merged technique of embedding MFC into a constructed wetland (CW) has been developed and appears to be increasingly investigated. The driving force to integrate these two technologies lies in the fact that CWs naturally possess a redox gradient (depending on flow direction and wetland depth), which is required by MFCs as anaerobic anode and aerobic cathode chambers. No doubt, the integration of MFC with a CW will upgrade the CW to allow it to be used for wastewater treatment and, simultaneously, electricity generation, making CWs more sustainable and environmentally friendly. Currently, published work shows that India, China, Ireland, Spain, Germany and Malaysia are involved in the development of this technology although it is in its infant stage and many technical issues are faced on system configuration, operation and maximisation of electricity production. This paper aims to provide an updated review and analysis of the CW-MFC development. Focuses are placed on the experience gained so far from different researchers in the literature and further research directions and proposals are discussed in great detail.
  7. Imafuku S, Zheng M, Tada Y, Zhang X, Theng C, Thevarajah S, et al.
    J. Dermatol., 2018 Jul;45(7):805-811.
    PMID: 29740870 DOI: 10.1111/1346-8138.14338
    A working group of dermatologists in Asian countries assessed the current status of psoriatic management in the region to prepare a consensus report on topical treatment in mild to moderate plaque psoriasis. Even though the association of psoriasis with systemic comorbidities is increasingly acknowledged, psoriasis is still lower in health-care priority lists in the region. The psychosocial impact of psoriasis may be greater in Asian countries due to cultural norms and social discrimination. Non-adherence to treatment is also common among Asians. The current care given to patients with mild to moderate psoriasis needs to be streamlined, enhanced and organized with a patient-centered care approach to achieve better outcomes. A comprehensive assessment of the disease severity and its impact on a patient's life is required before initiating treatment. Education and active involvement of the patient in the treatment plan is an important part of psoriatic management. It is recommended to personalize topical treatment to meet the needs of the patient, depending on disease severity, psychosocial impact, the patient's expectations and, more importantly, the patient's willingness and ability to actively follow the treatment procedure. Fixed-dose combination of corticosteroid and vitamin D analogs is the preferred topical medication for both initial and maintenance phases of treatment. The fast containment of the disease is the goal of the initial phase of 4-8 weeks and it demands a potent fast-acting topical therapy. Satisfactory control of the disease and prevention of relapses should be achieved during the maintenance phase with twice a week or weekend applications.
  8. Zhao Y, Tan EK, Law HY, Yoon CS, Wong MC, Ng I
    Clin. Genet., 2002 Dec;62(6):478-81.
    PMID: 12485197
    We report the prevalence and ethnic differences of autosomal-dominant cerebellar ataxia (ADCA) in Singapore. Amongst 204 patients with ataxia who underwent genetic testing for dentatorubral-pallidoluysian atrophy (DRPLA) and for spinocerebellar ataxias (SCA) 1, 2, 3, 6, 7, 8, 10 and 12, 58 (28.4%) patients from 36 families tested positive. SCA 3 was identified in 31 (53.4%) patients from 15 families, SCA 2 in 17 (29.3%) patients from 12 families and SCA 1 in four (6.9%) patients from four families. Other SCA subtypes were rare. SCA 2 was the only subtype identified amongst ethnic Malay and ethnic Indian families. The estimated prevalence of ADCA in Singaporean families was at least 1 : 27,000. Based on the history and ancestry of Singaporeans, our study supported a founder effect for specific SCA subtypes and the association of ethnicity-specific SCA subtypes. Our findings suggest that SCA 2 is relatively common amongst the Malay race and that priority testing for SCA 3 and SCA 2 for ethnic Chinese, and SCA 2 for ethnic Malay, may be cost effective and relevant for the region.
  9. Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.
    Sci Rep, 2014;4:4061.
    PMID: 24515248 DOI: 10.1038/srep04061
    Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.
  10. Naderali N, Nejat N, Vadamalai G, Davis RE, Wei W, Harrison NA, et al.
    Int. J. Syst. Evol. Microbiol., 2017 Oct;67(10):3765-3772.
    PMID: 28905707 DOI: 10.1099/ijsem.0.002187
    Landscape-grown foxtail palm (Wodyetia bifurcata A. K. Irvine) trees displaying symptoms of severe foliar chlorosis, stunting, general decline and mortality reminiscent of coconut yellow decline disease were observed in Bangi, Malaysia, during 2012. DNA samples from foliage tissues of 15 symptomatic palms were analysed by employing a nested PCR assay primed by phytoplasma universal ribosomal RNA operon primer pairs, P1/P7 followed by R16F2n/R2. The assay yielded amplicons of a single band of 1.25 kb from DNA samples of 11 symptomatic palms. Results from cloning and sequence analysis of the PCR-amplified 16S rRNA gene segments revealed that, in three palms, three mutually distinct phytoplasmas comprising strains related to 'Candidatus Phytoplasma asteris' and 'Candidatus Phytoplasma cynodontis', as well as a novel phytoplasma, were present as triple infections. The 16S rRNA gene sequence derived from the novel phytoplasma shared less than 96 % nucleotide sequence identity with that of each previously describedspecies of the provisional genus 'Ca. Phytoplasma', justifying its recognition as the reference strain of a new taxon, 'Candidatus Phytoplasma wodyetiae'. Virtual RFLP profiles of the R16F2n/R2 portion of the 16S rRNA gene and the pattern similarity coefficient value (0.74) supported the delineation of 'Ca. Phytoplasma wodyetiae' as the sole representative subgroup A member of a new phytoplasma ribosomal group, 16SrXXXVI.
  11. Zhang Y, Xu W, Guo H, Zhang Y, He Y, Lee SH, et al.
    Cancer Res., 2017 Apr 17.
    PMID: 28416482 DOI: 10.1158/0008-5472.CAN-16-1633
    Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166(+)CD49f(hi)CD104(-)Lin(-) LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease.
  12. Nurul Farhana S, Muchlisin ZA, Duong TY, Tanyaros S, Page LM, Zhao Y, et al.
    Sci Rep, 2018 Jul 17;8(1):10787.
    PMID: 30018357 DOI: 10.1038/s41598-018-29049-7
    Members of the freshwater halfbeak genus Dermogenys are hard to identify to the species level, despite several previous attempts to isolate fixed meristic, morphometric and colour pattern differences. This has led to ongoing confusion in scientific literature, records of species occurrence, and entries in museum collections. Here, a DNA barcoding study was conducted on the genus to gain further understanding of its taxonomic status across the Southeast Asian region. Fish were collected from 33 localities, spanning freshwater and brackish habitats in Malaysia, Western Indonesia, Thailand and Vietnam. In total, 290 samples of Dermogenys spp. were amplified for a 651 base pair fragment of the mitochondrial cytochrome oxidase c subunit I (COI) gene. Analysis was able to successfully differentiate the three species: D. collettei, D. siamensis, D. sumatrana; reveal the presence of a new putative species, Dermogenys sp., that was sampled in sympatry with D. collettei at three locations; as well as uncovering two genetic lineages of a fifth species, D. bispina, that display non-overlapping geographical distributions in drainages of northern Borneo; Kudat and Sandakan. This study expands the barcode library for Zenarchopteridae, demonstrates the efficacy of DNA barcoding techniques for differentiating Dermogenys species, and the potential thereof in species discovery.
  13. Gopalai AA, Lim SY, Chua JY, Tey S, Lim TT, Mohamed Ibrahim N, et al.
    Biomed Res Int, 2014;2014:867321.
    PMID: 25243190 DOI: 10.1155/2014/867321
    The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.
  14. Gopalai AA, Lim SY, Aziz ZA, Lim SK, Tan LP, Chong YB, et al.
    Ann. Acad. Med. Singap., 2013 May;42(5):237-40.
    PMID: 23771111
    The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.
  15. Gopalai AA, Ahmad-Annuar A, Li HH, Zhao Y, Lim SY, Tan AH, et al.
    PMID: 27174169 DOI: 10.1002/ajmg.b.32454
    PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.
  16. Wu CH, McCloskey EV, Lee JK, Itabashi A, Prince R, Yu W, et al.
    J Clin Densitom, 2014 Jan-Mar;17(1):150-5.
    PMID: 23916756 DOI: 10.1016/j.jocd.2013.06.002
    The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.
  17. van Doorslaer E, O'Donnell O, Rannan-Eliya RP, Somanathan A, Adhikari SR, Garg CC, et al.
    Health Econ, 2007 Nov;16(11):1159-84.
    PMID: 17311356
    Out-of-pocket (OOP) payments are the principal means of financing health care throughout much of Asia. We estimate the magnitude and distribution of OOP payments for health care in fourteen countries and territories accounting for 81% of the Asian population. We focus on payments that are catastrophic, in the sense of severely disrupting household living standards, and approximate such payments by those absorbing a large fraction of household resources. Bangladesh, China, India, Nepal and Vietnam rely most heavily on OOP financing and have the highest incidence of catastrophic payments. Sri Lanka, Thailand and Malaysia stand out as low to middle income countries that have constrained both the OOP share of health financing and the catastrophic impact of direct payments. In most low/middle-income countries, the better-off are more likely to spend a large fraction of total household resources on health care. This may reflect the inability of the poorest of the poor to divert resources from other basic needs and possibly the protection of the poor from user charges offered in some countries. But in China, Kyrgyz and Vietnam, where there are no exemptions of the poor from charges, they are as, or even more, likely to incur catastrophic payments.
  18. Yang J, Siri JG, Remais JV, Cheng Q, Zhang H, Chan KKY, et al.
    Lancet, 2018 05 26;391(10135):2140-2184.
    PMID: 29678340 DOI: 10.1016/S0140-6736(18)30486-0
  19. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al.
    Lancet, 2014 Sep 13;384(9947):1005-70.
    PMID: 25059949 DOI: 10.1016/S0140-6736(14)60844-8
    BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

    METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

    FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

    INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

    FUNDING: Bill & Melinda Gates Foundation.

  20. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al.
    Lancet, 2014 Sep 13;384(9947):980-1004.
    PMID: 24797575 DOI: 10.1016/S0140-6736(14)60696-6
    BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

    METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.

    FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.

    INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

    FUNDING: Bill & Melinda Gates Foundation.

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