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      Incidence and Risk Factors for Neonatal Tetanus in Admissions to Kilifi County Hospital, Kenya

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          Abstract

          Background

          Neonatal Tetanus (NT) is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya.

          Methods

          We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999–2013) and identified cases of NT (standard clinical case definition) admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were tested for anti-tetanus antibodies.

          Results

          There were 191 NT admissions, of whom 187 (98%) were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81–0.89), P<0.001) but the case fatality (62%) did not change over the study period (P = 0.536). Younger infant age at admission (P = 0.001) was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82%) had undetectable levels of antitetanus antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate without protective levels.

          Conclusions

          Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to expand coverage.

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          Most cited references33

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          4 million neonatal deaths: when? Where? Why?

          The proportion of child deaths that occurs in the neonatal period (38% in 2000) is increasing, and the Millennium Development Goal for child survival cannot be met without substantial reductions in neonatal mortality. Every year an estimated 4 million babies die in the first 4 weeks of life (the neonatal period). A similar number are stillborn, and 0.5 million mothers die from pregnancy-related causes. Three-quarters of neonatal deaths happen in the first week--the highest risk of death is on the first day of life. Almost all (99%) neonatal deaths arise in low-income and middle-income countries, yet most epidemiological and other research focuses on the 1% of deaths in rich countries. The highest numbers of neonatal deaths are in south-central Asian countries and the highest rates are generally in sub-Saharan Africa. The countries in these regions (with some exceptions) have made little progress in reducing such deaths in the past 10-15 years. Globally, the main direct causes of neonatal death are estimated to be preterm birth (28%), severe infections (26%), and asphyxia (23%). Neonatal tetanus accounts for a smaller proportion of deaths (7%), but is easily preventable. Low birthweight is an important indirect cause of death. Maternal complications in labour carry a high risk of neonatal death, and poverty is strongly associated with an increased risk. Preventing deaths in newborn babies has not been a focus of child survival or safe motherhood programmes. While we neglect these challenges, 450 newborn children die every hour, mainly from preventable causes, which is unconscionable in the 21st century.
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            Placental transport of immunoglobulin G

            Maternal antibodies transported across the placenta protect the newborn. Maternal immunoglobulin G (IgG) concentrations in fetal blood increase from early in the second trimester through term, most antibodies being acquired during the third trimester. IgG1 is the most efficiently transported subclass and IgG2 the least. Transfer across the syncytiotrophoblast of the chorionic villi is mediated by the neonatal Fc receptor, FcRn. Immune complexes are absorbed in the stroma of the villi, probably by FcgammaRI, FcgammaRII, and FcgammaRIII on placental macrophages. The mechanism of IgG transport across the endothelium of fetal capillaries is not understood. Endothelial cells in terminal villi express FcgammaRIIb. However, it is not known whether this receptor transports IgG or prevents transport of immune complexes to the fetus.
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              Profile: The Kilifi Health and Demographic Surveillance System (KHDSS)

              Summary The Kilifi Health and Demographic Surveillance System (KHDSS), located on the Indian Ocean coast of Kenya, was established in 2000 as a record of births, pregnancies, migration events and deaths and is maintained by 4-monthly household visits. The study area was selected to capture the majority of patients admitted to Kilifi District Hospital. The KHDSS has 260 000 residents and the hospital admits 4400 paediatric patients and 3400 adult patients per year. At the hospital, morbidity events are linked in real time by a computer search of the population register. Linked surveillance was extended to KHDSS vaccine clinics in 2008. KHDSS data have been used to define the incidence of hospital presentation with childhood infectious diseases (e.g. rotavirus diarrhoea, pneumococcal disease), to test the association between genetic risk factors (e.g. thalassaemia and sickle cell disease) and infectious diseases, to define the community prevalence of chronic diseases (e.g. epilepsy), to evaluate access to health care and to calculate the operational effectiveness of major public health interventions (e.g. conjugate Haemophilus influenzae type b vaccine). Rapport with residents is maintained through an active programme of community engagement. A system of collaborative engagement exists for sharing data on survival, morbidity, socio-economic status and vaccine coverage.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 April 2015
                2015
                : 10
                : 4
                : e0122606
                Affiliations
                [1 ]KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Kilifi, Kenya
                [2 ]Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
                [3 ]International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa
                [4 ]Division of Immunology, University of Cape Town, Cape Town, South Africa
                [5 ]Department of Psychiatry, University of Oxford, Oxford, United Kingdom
                University of Cambridge, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CRJCN. Performed the experiments: JL MM MB JRD EB. Analyzed the data: FI SMK GF RO KM JRD ACS JAB CRJCN. Contributed reagents/materials/analysis tools: JRD CRJCN. Wrote the paper: FI EB SMK GF JL MM MB RO KM JRD ACS JAB CRJCN.

                Article
                PONE-D-14-52925
                10.1371/journal.pone.0122606
                4388671
                25849440
                777ec5b2-80fb-406b-a7bf-4a933a680f99
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 27 November 2014
                : 11 February 2015
                Page count
                Figures: 1, Tables: 3, Pages: 13
                Funding
                This study was supported by the Wellcome Trust Senior Clinical Fellowship to Professor Charles Newton (No. 083744). Symon Kariuki was supported by the Wellcome Trust training fellowship (099782), Fredrick Ibinda by the Wellcome Trust masters training fellowship (101140), and James Berkley by the Wellcome Trust intermediate clinical fellowship (083579). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                All relevant data are within the paper and its Supplementary files.

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