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  • 1. Adeniran, Abosede
    et al.
    Likaka, Andrew
    Knutsson, Anneka
    Costello, Anthony
    Daelmans, Bernadette
    Maliqi, Blerta
    Burssa, Daniel
    Freer, Joseph
    Askew, Ian
    Bowen, Lisa
    Kak, Lily
    McDougall, Lori
    Zaka, Nabila
    Tunçalp, Özge
    Tenhoope-Bender, Petra
    Syed, Shamsuzzoha Babar
    Swartling Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Luchesi, Thiago
    Zeck, Willibald
    Were, Wilson
    Barker, Pierre
    Naimy, Zainab
    Leadership, action, learning and accountability to deliver quality care for women, newborns and children.2018In: Bulletin of the World Health Organization, ISSN 0042-9686, E-ISSN 1564-0604, Vol. 96, no 3, p. 222-224Article in journal (Refereed)
  • 2.
    Algady, Walid
    et al.
    Univ Leicester, Dept Genet & Genome Biol, Leicester LE1 7RH, Leics, England.
    Louzada, Sandra
    Wellcome Sanger Inst, Cambridge CB10 1SA, England.
    Carpenter, Danielle
    Univ Leicester, Dept Genet & Genome Biol, Leicester LE1 7RH, Leics, England.
    Brajer, Paulina
    Univ Leicester, Dept Genet & Genome Biol, Leicester LE1 7RH, Leics, England.
    Farnert, Anna
    Karolinska Inst, Dept Med Solna, Div Infect Dis, S-17176 Stockholm, Sweden;Karolinska Univ Hosp, Dept Infect Dis, S-17176 Stockholm, Sweden.
    Rooth, Ingegerd
    Natl Inst Med Res, Nyamisati Malaria Res, Dar Es Salaam, Tanzania.
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.
    Yang, Fengtang
    Wellcome Sanger Inst, Cambridge CB10 1SA, England.
    Shaw, Marie-Anne
    Univ Leeds, Leeds Inst Med Res St Jamess, Leeds LS9 7TF, W Yorkshire, England.
    Hollox, Edward J.
    Univ Leicester, Dept Genet & Genome Biol, Leicester LE1 7RH, Leics, England.
    The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels2018In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, no 5, p. 769-776Article in journal (Refereed)
    Abstract [en]

    Glycophorin A and glycophorin B are red blood cell surface proteins and are both receptors for the parasite Plasmodium falciparum, which is the principal cause of malaria in sub-Saharan Africa. DUP4 is a complex structural genomic variant that carries extra copies of a glycophorin A-glycophorin B fusion gene and has a dramatic effect on malaria risk by reducing the risk of severe malaria by up to 40%. Using fiber-FISH and Illumina sequencing, we validate the structural arrangement of the glycophorin locus in the DUP4 variant and reveal somatic variation in copy number of the glycophorin B-glycophorin A fusion gene. By developing a simple, specific, PCR-based assay for DUP4, we show that the DUP4 variant reaches a frequency of 13% in the population of a malaria-endemic village in southeastern Tanzania. We genotype a substantial proportion of that village and demonstrate an association of DUP4 genotype with hemoglobin levels, a phenotype related to malaria, using a family-based association test. Taken together, we show that DUP4 is a complex structural variant that may be susceptible to somatic variation and show that DUP4 is associated with a malarial-related phenotype in a longitudinally followed population.

  • 3. Allen, Elizabeth Palchik
    et al.
    Muhwezi, Wilson Winstons
    Henriksson, Dorcus Kiwanuka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Karolinska Institutet, Sweden..
    Mbonye, Anthony Kabanza
    Health facility management and access: a qualitative analysis of challenges to seeking healthcare for children under five in Uganda2017In: Health Policy and Planning, ISSN 0268-1080, E-ISSN 1460-2237, Vol. 32, no 7, p. 934-942Article in journal (Refereed)
    Abstract [en]

    While several studies have documented the various barriers that caretakers of children under five routinely confront when seeking healthcare in Uganda, few have sought to capture the ways in which caretakers themselves prioritize their own barriers to seeking services. To that end, we asked focus groups of caretakers to list their five greatest challenges to seeking care on behalf of children under five. Using qualitative content analysis, we grouped responses according to four categories: (1) geographical access barriers; (2) facility supplies, staffing, and infrastructural barriers; (3) facility management and administration barriers (e.g. health worker professionalism, absenteeism and customer care); and (4) household barriers related to financial circumstances, domestic conflicts with male partners and a stated lack of knowledge about health-related issues. Among all focus groups, caretakers mentioned supplies, staffing and infrastructure barriers most often and facility management and administration barriers the least. Caretakers living furthest from public facilities (8-10 km) more commonly mentioned geographical barriers to care and barriers related to financial and other personal circumstances. Caretakers who lived closest to health facilities mentioned facility management and administration barriers twice as often as those who lived further away. While targeting managerial barriers is vitally important-and increasingly popular among national planners and donors-it should be done while recognizing that alleviating such barriers may have a more muted effect on caretakers who are geographically harder to reach - and by extension, those whose children have an increased risk of mortality. In light of calls for greater equity in child survival programming - and given the limited resource envelopes that policymakers often have at their disposal - attention to the barriers considered most vital among caretakers in different settings should be weighed.

  • 4.
    Almblad, Ann-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Brylid, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Increased intensive care admission rate after introduction of Early Detection and Treatment program for Children and the establishment of a pediatric intensive care unit at a tertiary hospital in SwedenIn: Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the introduction of an Early Detection and Treatment program- Children (EDT-C) including a paediatric early warning score (PEWS) in relation to admission and length of stay at intensive care unit (ICU). Design: Before-after study utilizing data from the Electronic Patient Record (EPR) system, comparing outcomes over a total time period of 60 months between April 2010 and September 2015. Setting: A Swedish tertiary hospital. Patients: A total of 16,283 paediatric patients were included over the study period. Interventions: EDT-C including PEWS Measurements and Main Results: The following variables were extracted from the EPR data: 1) Admissions to paediatric wards 2) Length of stay at paediatric wards 3) Admissions to intensive care units 4) Length of stay at intensive care unit 5) Diagnosis. Intensive care unit admission increased from 5.0% (440/8746) before to 10.2 % (772/7537) after the introduction of the EDT-C (p<0.01). Mean treatment time at ICU did not change (41.0 vs 48.3 hours, p=0.23). Conclusion: The introduction of EDT-C including PEWS, in conjunction with the establishment of a paediatric intensive care unit at the hospital, resulted in an increased intensive care admittance rate among paediatric in-patients.

  • 5.
    Almblad, Ann-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    From skepticism to assurance and control: Implementation of a patient safety system at a pediatric hospital in Sweden2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0207744Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of evidence-based practice among healthcare professionals directly correlates to better outcomes for patients and higher professional satisfaction. Translating knowledge in practice and mobilizing evidence-based clinical care remains a continuing challenge in healthcare systems across the world.

    PURPOSE: To describe experiences from the implementation of an Early Detection and Treatment Program for Children (EDT-C) among health care professionals at a pediatric hospital in Sweden.

    DESIGN AND METHODS: Sixteen individual interviews were conducted with physicians, nurses and nurse assistants, which of five were instructors. Data were analyzed with qualitative content analysis.

    RESULTS: An overarching theme was created: From uncertainty and skepticism towards assurance and control. The theme was based on the content of eight categories: An innovation suitable for clinical practice, Differing conditions for change, Lack of organizational slack, Complex situations, A pragmatic implementation strategy, Delegated responsibility, Experiences of control and Successful implementation.

    CONCLUSIONS: Successful implementation was achieved when initial skepticism among staff was changed into acceptance and using EDT-C had become routine in their daily work. Inter-professional education including material from authentic patient cases promotes knowledge about different professions and can strengthen teamwork. EDT-C with evidenced-based material adapted to the context can give healthcare professionals a structured and objective tool with which to assess and treat patients, giving them a sense of control and assurance.

  • 6.
    Almblad, Ann-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    From skepticism to assurance and control: implementation of a patient safety system at a pediatric hospital in SwedenIn: Article in journal (Refereed)
  • 7.
    Almblad, Ann-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Siltberg, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Implementation of Pediatric Early Warning Score: Adherence to Guidelines and Influence of Context2018In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 38, p. 33-39Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe data of Pediatric Early Warning Score (PEWS) registrations and to evaluate the implementation of PEWS by examining adherence to clinical guidelines based on measured PEWS, and to relate findings to work context.

    DESIGN AND METHODS: PEWS, as a part of a concept called Early Detection and Treatment-Children (EDT-C) was implemented at three wards at a Children's Hospital in Sweden. Data were collected from the Electronic Patient Record (EPR) retrospectively to assess adherence to guidelines. The Alberta Context Tool (ACT) was used to assess work context among healthcare professionals (n=110) before implementation of EDT-C.

    RESULTS: The majority of PEWS registrations in EPR were low whereas 10% were moderate to high. Adherences to ward-specific guidelines at admission and for saturation in respiratory distress were high whereas adherence to pain assessment was low. There were significant differences in documented recommended actions between wards. Some differences in leadership and evaluation between wards were identified.

    CONCLUSIONS: Evaluation of PEWS implementation indicated frequent use of the tool despite most scores being low. High scores (5-9) occurred 28 times, which may indicate that patients with a high risk of clinical deterioration were identified. Documentation of the consequent recommended actions was however incomplete and there was a large variation in adherence to guidelines. Contextual factors may have an impact on adherence.

    PRACTICE IMPLICATIONS: EDT-C can lead to increased knowledge about early detection of deterioration, strengthen nurses as professionals, optimize treatment and teamwork and thereby increase patient safety for children treated in hospitals.

  • 8.
    Andersson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Between the sheets - or how to keep babies warm2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 8, p. 1300-1301Article in journal (Other academic)
  • 9.
    Arifeen, Shams El
    et al.
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Frongillo, Edward A
    Univ South Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC USA.
    Hamadani, Jena
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Khan, Ashraful Islam
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Naved, Ruchira T
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Rahman, Anisur
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Raqib, Rubhana
    Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh.
    Rasmussen, Kathleen M
    Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Wagatsuma, Yukiko
    Univ Tsukuba, Dept Med, Tsukuba, Ibaraki, Japan.
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. London Sch Hyg & Trop Med, Dept Dis Control, London, England.
    Cohort Profile: The Maternal and Infant Nutrition Interventions in Matlab (MINIMat) Cohort in Bangladesh2018In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 47, no 6, p. 1737-1738eArticle in journal (Refereed)
  • 10.
    Bergström, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Ugarte Guevara, William J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Maternal and Reproductive Health and Migration.
    Eustachio Colombo, Patricia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Knowledge about Sexual and Reproductive Health among School Enrolled Adolescents in Tololar, Nicaragua, A Cross-Sectional Study2018In: Journal of Public Health International, Vol. 1, no 2, p. 27-38Article in journal (Refereed)
    Abstract [en]

    Background: Nicaragua has the highest prevalence of teenage pregnancies in Latin America. Knowledge regarding sexual and reproductive health plays an integral part in sexual behavior. The objective was to assess school going adolescents' knowledge about sexual and reproductive health and possible factors affecting it in the semi-rural community of Tololar, Nicaragua.

    Methods: A cross-sectional study with a self-administered questionnaire on tablets was used for data collection. All 253 registered students at the school present at the time of fieldwork who gave written informed consent were deemed eligible for the study. A total of 225 participants in the ages of 11-19 years were included. Simple linear regression and multiple linear regression were performed analyzing the outcome knowledge. A p-value <0.05 was considered significant.

    Results: The general knowledge about sexual and reproductive health was moderate; however, knowledge gaps were found such as prevailing myths and poor knowledge regarding human immunodeficiency virus (hiv) transmission and contraceptive methods. Being female and single were significant negative determinants of knowledge (p-value < 0.01) and knowledge increased significantly with age (p-value < 0.05). School teachers, websites, social networks, and TV were the most frequently chosen sources of information on the topic.

    Conclusions: Increased education on sexual and reproductive health with new interventions particularly for young females is recommended. Using IT-based materials as a complement may be an effective way to reach out to adolescents.

  • 11.
    Berhane, Hanna Y
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Jirström, Magnus
    Berhane, Yemane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Turner, Christopher
    Alsanius, Beatrix W
    Trenholm, Jill E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Maternal and Reproductive Health and Migration.
    Mixed blessings:: A qualitative exploration of mothers' experience of child care and feeding in the rapidly urbanizing city of Addis Ababa, Ethiopia2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0207685Article in journal (Refereed)
    Abstract [en]

    Many studies have drawn attention to the vital role mothers have in safeguarding the health and nutritional wellbeing of their children. However, little is known about mothers' experiences and the challenges they face in fulfilling this role in rapidly urbanizing cities in Africa. This study aims to explore child care and feeding practices of mothers with children under five years of age in Addis Ababa, Ethiopia. This qualitative study was conducted using a semi-structured interview guide. A total of thirty-six interviews were conducted with purposively selected participants. All interviews were audio recorded, transcribed verbatim and translated for analysis. We used a thematic analysis approach, which was guided by a resilience framework. The findings are presented as three major themes. 1) 'Mixed blessings-balancing motherhood's expectations'. While mothers identified positively with the social recognition and sense of fulfillment of being a 'good mother', they were ambivalent/torn about earning the necessary income from outside work and fulfilling their duties at home. 2) 'Instabilities due to rampant urban sprawl'. While women expressed a keen desire to balance work and motherhood, the disintegrating social capital, due to large in-migration, market fluctuations and abrupt/forced resettlements to new housing units had left mothers without support for childcare, stressed and exhausted. 3) 'Anchored by faith: a source of resilience to cope with adversities'. In the face of the multiple adversities, mothers cited their strong faith as their most reliable foundation for their resilience. In summary, the societal and environmental changes accompanying the rapid urbanization in low income settings makes combining child care and working outside the home very challenging for mothers. As a result they suffer from fatigue and feelings of isolation. Efforts to improve child feeding and care in urban low-income settings need to consider context appropriate strategies that support mothers with small children.

  • 12.
    Berhane, Hanna Y
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Addis Continental Inst Publ Hlth, Addis Ababa 267511000, Ethiopia.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Jirström, Magnus
    Lund Univ, Dept Human Geog, S-22362 Lund, Sweden.
    Berhane, Yemane
    Addis Continental Institute of Public Health, 26751/1000 Addis Ababa, Ethiopia.
    Turner, Christopher
    Lund Univ, Dept Human Geog, S-22362 Lund, Sweden;London Sch Hyg & Trop Med, London WC1E 7HT, England.
    Alsanius, Beatrix W
    Swedish Univ Agr Sci, Dept Biosyst & Technol, S-23053 Alnarp, Sweden.
    Trenholm, Jill E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Maternal and Reproductive Health and Migration.
    What Influences Urban Mothers' Decisions on What to Feed Their Children Aged Under Five-The Case of Addis Ababa, Ethiopia2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 9, article id 1142Article in journal (Refereed)
    Abstract [en]

    Mothers carry the prime responsibility for childcare and feeding in low-income countries. Understanding their experiences in providing food for their children is paramount to informing efforts to improve the nutritional status of children. Such information is lacking in Sub-Saharan Africa. To understand what influences urban mothers' food acquisition and their motivations for selecting food for their children, 36 in-depth interviews were carried out with mothers having children under five years of age. Interviews were conducted in the local language, audio-recorded, transcribed, and translated into English. Data were analyzed using thematic analysis which led to the identification of four major themes: mothers give-in to a child-driven diet; quick-fix versus the privilege of planning; keen awareness on food safety, nutrition, and diet diversity; and social, familial, and cultural influences. The findings indicate that child feeding practices are influenced by interlinked social and environmental factors. Hence, nutrition education campaigns should focus on targeting not only families but also their children. Attention should also be given to food safety regulations, as well as to the much-needed support of mothers who are struggling to ensure their children's survival in low-income countries.

  • 13.
    Bogale, Tesfahun Yonas
    et al.
    Wolaita Sodo Univ, Hlth Sci & Med Coll, Wolaita Sodo, Ethiopia.
    Tadesse Balla, Elazar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Tadesse, Minyahil
    Wolaita Sodo Univ, Hlth Sci & Med Coll, Wolaita Sodo, Ethiopia.
    Asamoah, Benedict Oppong
    Lund Univ, Dept Clin Sci, Social Med & Global Hlth, Malmo, Sweden.
    Prevalence and associated factors for stunting among 6-12 years old school age children from rural community of Humbo district, Southern Ethiopia2018In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 18, article id 653Article in journal (Refereed)
    Abstract [en]

    Background: Stunting is one of the most serious and challenging public health problems in Ethiopia, which constitute a significant obstacle to achieving better child health outcomes. This study aimed to assess the prevalence and factors associated with stunting among 6-12 years old children in Humbo district, Southern Ethiopia. Methods: This was a cross-sectional study conducted among 633 children 6-12 years old living in Humbo district, Southern Ethiopia, from March to April, 2015. A multistage cluster sampling technique was used to select participants from households in eight Villages in the study area. Height was measured using standard methods and height for age Z-score was computed to assess stunting. EPI info version 3.5.4 was used for data entry, whereas Anthroplus software and SPSS version 20.0 were used for computation of height for age Z-scores and statistical analyses respectively. Simple and multiple logistic regression analyses were used to examine factors associated with stunting in the study sample, using 95% confidence limits (statistical significance set at p < 0.050). Results: Prevalence of stunting was 57%, about, 3.5% were severely stunted, 27.3% moderately stunted and 26.4% mildly stunted, and the mean (SD) was -1.1 (+/- 1.2). About 7 (1.1%) boys and 15 (2.4%) girls were severely stunted. Age groups 10-12 years had significantly higher rate of stunting than others. Age (AOR = 1.7, 95% CI = 1.1-2.6), big family size (AOR = 4.6, 95% CI = 2.2-9.5) and field disposal of wastes (AOR = 2.7, 95% CI = 1.2-5.8) were factors significantly associated with stunting. Conclusion: This study exposed high rate of stunting among school age children. Stunting remains a noticeable attribute of rural school age children. Findings suggest the need to implement evidence-based school-aged rural children nutrition policy and strategies as well as need for intervention to improve domestic waste management system in the rural community.

  • 14.
    Bui, Ha Thi Thu
    et al.
    Hanoi Univ Publ Hlth, Fac Social Sci Behav & Hlth Educ, Hanoi, Vietnam.
    Le, Thi Minh
    Hanoi Univ Publ Hlth, Fac Social Sci Behav & Hlth Educ, Hanoi, Vietnam.
    Pham, Tac Van
    Minist Hlth, Hanoi, Vietnam.
    Doan, Duong Thi Thuy
    Hanoi Univ Publ Hlth, Fac Social Sci Behav & Hlth Educ, Hanoi, Vietnam.
    Nguyen, Duy Anh
    Hanoi Obstet & Gynecol Hosp, Hanoi, Vietnam.
    Nguyen, Canh Chuong
    Hanoi Obstet & Gynecol Hosp, Hanoi, Vietnam.
    Duc, Duong Minh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Hanoi Univ Publ Hlth, Fac Social Sci Behav & Hlth Educ, Hanoi, Vietnam.
    The Association Between Gender Inequalities and Women's Utilization of Maternal Health Services: A Cross-Sectional Survey in Eight South Central Coast Provinces, Vietnam2018In: Journal of Public Health Management and Practice, ISSN 1078-4659, E-ISSN 1550-5022, Vol. 24, no 2, p. S19-S27Article in journal (Refereed)
    Abstract [en]

    Background: Gender inequalities influence the utilization of maternal health services in Vietnam, but little research has been published. This study, therefore, aimed to explore the association between gender inequalities and women's utilization of maternal health services in Vietnam.

    Methods: The study was conducted in 8 provinces in the South Central Coast region of Vietnam during August 2013 to May 2014. A total of 907 women who delivered a year prior to the date of interview participated in the study. A multiple logistic regression model was used to examine the association between gender inequalities (including sociodemographic determinants of health) and utilization of 4 or more antenatal care (ANC4+) services, institutional delivery, and ever used contraceptive methods.

    Results: The utilization rate of maternal health services was varied, from 53.9% for ANC4+ to 87.7% for ever used a contraceptive method and 97% for institutional delivery. Ethnicity was identified as the most influential variable out of all sociodemographic determinants of health. Regarding gender inequalities, couple communication was the only variable having significant association with women's utilization of maternal health services.

    Conclusion: Women's equal role within context of their daily life and relations with their husbands (discussing maternal care with husband and having equal income to husband) supported their use of maternal health services. Therefore, there should be concerted efforts from all relevant stakeholders including the health system to focus on disadvantaged women in planning and delivery of maternal health services, especially to ethnic minority women. Male involvement strategy should be implemented to promote maternal health care, especially during the prenatal and postpartum period. To provide more culturally sensitive and right-based approaches in delivery of maternal health services to disadvantaged women in Vietnam, interventions are recommended that promote male involvement, that is, to engage men in service delivery to adapt and ensure the most appropriate and effective maternal health care.

  • 15.
    Bychkov, Dmitrii
    et al.
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Linder, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Turkki, Riku
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Nordling, Stig
    Univ Helsinki, Dept Pathol, Med, Helsinki, Finland..
    Kovanen, Panu E.
    Univ Helsinki, Dept Pathol, Helsinki, Finland.;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland..
    Verrill, Clare
    Univ Oxford, Nuffield Dept Surg Sci, NIHR Oxford Biomed Res Ctr, Oxford, England..
    Walliander, Margarita
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Lundin, Mikael
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Haglund, Caj
    Univ Helsinki, Dept Surg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Translat Canc Biol, Helsinki, Finland..
    Lundin, Johan
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.;Karolinska Inst, Dept Publ Hlth Sci, Global Hlth IHCAR, Stockholm, Sweden..
    Deep learning based tissue analysis predicts outcome in colorectal cancer2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3395Article in journal (Refereed)
    Abstract [en]

    Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79-3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28-2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30-2.15; AUC 0.57) in the stratification into low-and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.

  • 16.
    Cotter, Chris
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Univ Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, 550 16th St,3rd Floor, San Francisco, CA 94158 USA.
    Sudathip, Prayuth
    Minist Publ Hlth, Dept Dis Control, Bur Vector Borne Dis, Nonthaburi, Thailand.
    Herdiana, Herdiana
    UN Childrens Fund UNICEF, Aceh Field Off, Banda Aceh, Indonesia;Paritrana Asia Fdn, Jakarta, Indonesia.
    Cao, Yuanyuan
    Jiangsu Inst Parasit Dis, Jiangsu Prov Key Lab Parasite & Vector Control Te, Key Lab, Natl Hlth & Family Planning Commiss Parasit Dis C, Wuxi, Jiangsu, Peoples R China.
    Liu, Yaobao
    Jiangsu Inst Parasit Dis, Jiangsu Prov Key Lab Parasite & Vector Control Te, Key Lab, Natl Hlth & Family Planning Commiss Parasit Dis C, Wuxi, Jiangsu, Peoples R China.
    Luo, Alex
    Univ Calif San Francisco, Global Hlth Sci, San Francisco, CA 94158 USA.
    Ranasinghe, Neil
    Thomson Reuters Ltd, London, England.
    Bennett, Adam
    Univ Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, 550 16th St,3rd Floor, San Francisco, CA 94158 USA;Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA.
    Cao, Jun
    Jiangsu Inst Parasit Dis, Jiangsu Prov Key Lab Parasite & Vector Control Te, Key Lab, Natl Hlth & Family Planning Commiss Parasit Dis C, Wuxi, Jiangsu, Peoples R China.
    Gosling, Roly D.
    Univ Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, 550 16th St,3rd Floor, San Francisco, CA 94158 USA;Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA.
    Piloting a programme tool to evaluate malaria case investigation and reactive case detection activities: results from 3 settings in the Asia Pacific2017In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, article id 347Article in journal (Refereed)
    Abstract [en]

    Background: Case investigation and reactive case detection (RACD) activities are widely-used in low transmission settings to determine the suspected origin of infection and identify and treat malaria infections nearby to the index patient household. Case investigation and RACD activities are time and resource intensive, include methodologies that vary across eliminating settings, and have no standardized metrics or tools available to monitor and evaluate them. Methods: In response to this gap, a simple programme tool was developed for monitoring and evaluating (M&E) RACD activities and piloted by national malaria programmes. During the development phase, four modules of the RACD M&E tool were created to assess and evaluate key case investigation and RACD activities and costs. A pilot phase was then carried out by programme implementers between 2013 and 2015, during which malaria surveillance teams in three different settings (China, Indonesia, Thailand) piloted the tool over a period of 3 months each. This study describes summary results of the pilots and feasibility and impact of the tool on programmes. Results: All three study areas implemented the RACD M&E tool modules, and pilot users reported the tool and evaluation process were helpful to identify gaps in RACD programme activities. In the 45 health facilities evaluated, 71.8% (97/135; min 35.3-max 100.0%) of the proper notification and reporting forms and 20.0% (27/135; min 0.0-max 100.0%) of standard operating procedures (SOPs) were available to support malaria elimination activities. The tool highlighted gaps in reporting key data indicators on the completeness for malaria case reporting (98.8%; min 93.3-max 100.0%), case investigations (65.6%; min 61.8-max 78.4%) and RACD activities (70.0%; min 64.7-max 100.0%). Evaluation of the SOPs showed that knowledge and practices of malaria personnel varied within and between study areas. Average monthly costs for conducting case investigation and RACD activities showed variation between study areas (min USD $844.80-max USD $2038.00) for the malaria personnel, commodities, services and other costs required to carry out the activities. Conclusion: The RACD M&E tool was implemented in the three pilot areas, identifying key gaps that led to impacts on programme decision making. Study findings support the need for routine M&E of malaria case reporting, case investigation and RACD activities. Scale-up of the RACD M&E tool in malaria-eliminating settings will contribute to improved programme performance to the high level that is required to reach elimination.

  • 17.
    Duc, Duong M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Hanoi University of Public Health, Vietnam.
    Eriksson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wallin, Lars
    School of Education, Health and Social Studies, Dalarna University, Sweden.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Cummings, Greta
    Faculty of Nursing, University of Alberta, Canada.
    Nga, Nguyen Thu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Bui, Ha
    Hanoi University of Public Health, Vietnam.
    Bergström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Measuring local healthcare context for knowledge translation in primary and secondary levels of care in northern Vietnam: A cross-sectional studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    The influence of context in shaping the effectiveness of knowledge translation (KT) is widely recognized. The Context Assessment for Community Health (COACH) tool aims to assess contextual aspects that are of importance for KT in healthcare in low- and middle-income settings. This study used the COACH tool to describe healthcare context as perceived by health workers in primary and secondary levels of care in a northern province in Vietnam and to further evaluate the internal structure of the COACH tool.

    Methods

    This cross-sectional study administered the COACH tool to 677 eligible health workers in primary and secondary levels of care. The relationships between individual background variables and COACH dimensions were analysed using binary logistic regression. Further, internal construct validity was calculated by a first-order independent cluster model confirmatory factor analysis (CFA).

    Results

    Overall, the healthcare context was perceived as supportive for KT. Gender, age, and geographic location showed significant relationships to one of the COACH dimensions. Male health workers rated their Commitment to work as lower than female health workers (OR=0.39, 95% CI: 0.20–0.78). There were, however, only minor differences in  scores for the dimensions of context, at each health facility as well as between health facilities. The CFA asserted an acceptable internal structure of the COACH tool.

    Conclusions

    The survey enhanced the understanding of how aspects of the healthcare context for KT are perceived by health workers at primary and secondary levels of care in a province in Vietnam. There was an overall positive perception of the work context with only minor variability, reflecting a ‘receptive to change’ context for KT. This should, however, be interpreted with caution due to the risk of social desirability response bias. The findings on the acceptable internal structure of the COACH tool supports its further use as a valid instrument. 

  • 18. Elfving, Kristina
    et al.
    Shakely, Deler
    Andersson, Maria
    Baltzell, Kimberly
    Msellem, Mwinyi I
    Björkman, Anders
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Petzold, Max
    Trollfors, Birger
    Lindh, Magnus
    Pathogen Clearance and New Respiratory Tract Infections Among Febrile Children in Zanzibar Investigated With Multitargeting Real-Time Polymerase Chain Reaction on Paired Nasopharyngeal Swab Samples.2018In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 37, no 7, p. 643-648Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children.

    METHODS: Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion.

    RESULTS: At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up.

    CONCLUSION: The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.

  • 19.
    Eltom, Mohamed A.
    et al.
    Mulazmin Diabet Ctr, Khartoum, Sudan.;Ahfad Univ Women, Khartoum, Sudan..
    Mohamed, Abubakr H. Babiker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Mulazmin Diabet Ctr, Khartoum, Sudan.;Ahfad Univ Women, Khartoum, Sudan..
    Elrayah-Eliadarous, Hind
    Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden..
    Yassin, Kamal
    Mulazmin Diabet Ctr, Khartoum, Sudan.;Ahfad Univ Women, Khartoum, Sudan..
    Noor, Sufian K.
    Nile Valley Univ, Dept Med, Fac Med & Hlth Sci, Khartoum, Sudan..
    Elmadhoun, Wadie M.
    Nile Valley Univ, Dept Med, Fac Med & Hlth Sci, Khartoum, Sudan..
    Ahmed, Mohamed H.
    Milton Keynes Univ Hosp NHS Fdn Trust, Dept Med, Milton Keynes, Bucks, England.;Milton Keynes Univ Hosp NHS Fdn Trust, HIV Metab Clin, Milton Keynes, Bucks, England..
    Increasing prevalence of type 2 diabetes mellitus and impact of ethnicity in north Sudan2018In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 136, p. 93-99Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes mellitus constitutes a global health threat, with increasing burden of disease in low and middle-income countries witnessing ongoing epidemiological transition including Sudan.

    Aims: To study the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes and determine the relationship to gender, age, waist circumference, body mass index, residence and ethnicity among the adult population in north Sudan.

    Methods: A cross-sectional, population-based study in Northern State and River Nile State using random multi-stage cluster sampling targeting 5376 participants from 14 localities divided into 60 urban and 40 rural clusters. In each cluster, 60 households were studied. Blood glucose level and anthropometric measurements were recorded and a questionnaire containing demographic data was obtained from each participant.

    Results: The prevalence of T2DM among participants was 18.7% and prediabetes was 12.9%. Among people living with T2DM, 694(71.0%) were known cases of T2DM, whereas 284 (29.0%) were newly diagnosed cases. The significant associated risk factors for T2DM included urban residence (AOR 1.23, 95% CI 1.09-1.41), age above 60 years (AOR 4.77, 95% CI 4.04-5.63), obese BMI (AOR 1.26, 95% CI 1.03-1.55) and central obesity (AOR 1.39, 95% CI 1.14-1.68). Compared to indigenous population, individuals of Egyptian descents (AOR 1.28, 95% CI 1.04-1.57) and mixed origin (AOR 1.24, 95% CI 1.04-1.48) had increased risk of T2DM.

    Conclusion: The prevalence of T2DM and prediabetes in north Sudan have increased significantly since 1996 with variations between ethnicities which showed to be an independent risk factor for T2DM. Health authorities are recommended to set plans to meet the health needs of these communities.

  • 20.
    Eriksson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nga, Nguyen T
    Research Institute for Child Health, Hanoi, Vietnam.
    Hoa, Dinh T Phuong
    Hanoi University of Public Health, Vietnam.
    Duc, Duong M
    Hanoi University of Public Health, Vietnam.
    Bergström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Institute for Global Health, University College London, London, UK.
    Wallin, Lars
    School of Education, Health and Social Studies, Dalarna University, Falun, Sweden.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Huy, Tran Q
    Department of Medical Services Administration, Ministry of Health, Nursing office, Hanoi, Vietnam.
    Thuy, Nguyen T
    Vietnam-Sweden Uong Bi General Hospital, Uong Bi, Vietnam.
    Do, Tran Thanh
    National Institute of Nutrition (NIN), Ministry of Health, Hanoi, Vietnam.
    Lien, Pham T L
    Research Institute for Child Health, Hanoi, Vietnam.
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. London School of Hygiene & Tropical Medicine, London, UK.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Secular trend, seasonality and effects of a community-based intervention on neonatal mortality: follow-up of a cluster-randomised trial in Quang Ninh province, Vietnam2018In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 72, no 9, p. 776-782Article in journal (Refereed)
    Abstract [en]

    Background: Little is know about whether the effects of community engagement interventions for child survival in low-income and middle-income settings are sustained. Seasonal variation and secular trend may blur the data. Neonatal mortality was reduced in a cluster-randomised trial in Vietnam where laywomen facilitated groups composed of local stakeholders employing a problem-solving approach for 3 years. In this analysis, we aim at disentangling the secular trend, the seasonal variation and the effect of the intervention on neonatal mortality during and after the trial.

    Methods: In Quang Ninh province, 44 communes were allocated to intervention and 46 to control. Births and neonatal deaths were assessed in a baseline survey in 2005, monitored during the trial in 2008–2011 and followed up by a survey in 2014. Time series analyses were performed on monthly neonatal mortality data.

    Results: There were 30 187 live births and 480 neonatal deaths. The intervention reduced the neonatal mortality from 19.1 to 11.6 per 1000 live births. The reduction was sustained 3 years after the trial. The control areas reached a similar level at the time of follow-up. Time series decomposition analysis revealed a downward trend in the intervention areas during the trial that was not found in the control areas. Neonatal mortality peaked in the hot and wet summers.

    Conclusions: A community engagement intervention resulted in a lower neonatal mortality rate that was sustained but not further reduced after the end of the trial. When decomposing time series of neonatal mortality, a clear downward trend was demonstrated in intervention but not in control areas.

    Trial registration number: ISRCTN44599712, Post-results.

  • 21.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Family-Centered Care: More than a Good Feeling?2017In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 112, no 3, p. 301-302Article in journal (Other academic)
  • 22.
    Frith, Amy
    et al.
    Ithaca Coll, Lansing, NY USA..
    Ziaei, Shirin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Frongillo, Edward
    Univ South Carolina, Hlth Promot Educ & Behav, Columbia, SC USA..
    Khan, Ashraful
    ICDDR B, Dhaka, Bangladesh..
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Naved, Ruchira
    ICDDR B, Dhaka, Bangladesh..
    Breastfeeding counseling improves maternal-infant feeding interaction in those exposed to controlling behavior or emotional violence: MINIMat study in Bangladesh2017In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 31, no 1, article id 959.11Article in journal (Other academic)
  • 23.
    Ghindilis, Andrey L.
    et al.
    TORCATECH LLC, 5210,104th St SW, Mukilteo, WA 98275 USA.
    Chesnokov, Olga
    Florida Atlantic Univ, Charles E Schmidt Coll Med, Dept Biomed Sci, 777 Glades Rd, Boca Raton, FL 33428 USA.
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.
    Smith, Maria W.
    TORCATECH LLC, 5210,104th St SW, Mukilteo, WA 98275 USA.
    Smith, Kenneth
    TORCATECH LLC, 5210,104th St SW, Mukilteo, WA 98275 USA.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Oleinikov, Andrew V.
    Florida Atlantic Univ, Charles E Schmidt Coll Med, Dept Biomed Sci, 777 Glades Rd, Boca Raton, FL 33428 USA.
    Detection of sub-microscopic blood levels of Plasmodium falciparum using Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) assay with an attomolar detection limit2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2901Article in journal (Refereed)
    Abstract [en]

    Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) based on signal rather than target amplification under isothermal conditions was developed for nucleic acid assays. The initial signal was generated by hybridization of single stranded DNA targets to immobilized recognition probes followed by hybrid cleavage with specific restriction endonuclease (REase), and release of trigger oligonucleotides (Tr1). The signal amplification chamber contained two bead types carrying single-stranded amplification probes and two amplification REases. The probes consisted of multiple tandem repeats of either Tr1 or another trigger Tr2, with the tandem-Tr1 anchored to the beads through the antisense Tr2 linker and vice versa. Addition of the recognition reaction solution and Tr1 hybridization to the anti-Tr1 linkers started cleavage and release of additional Tr1 and Tr2, resulting in exponential signal amplification. The cleavage cascade also released horseradish peroxidase (HRP) pre-attached to the amplification probes, and the resultant signal was measured colorimetrically. A TORCA assay was developed for detection of Plasmodium falciparum parasites in blood. It had the detection limit in the attomolar concentration range, successfully detecting sub-microscopic P. falciparum infections at less than 0.75 infected erythrocytes per microliter. Further TORCA optimization will likely produce the quantitative isothermal alternative to PCR at a fraction of its cost.

  • 24.
    Holmström, Oscar
    et al.
    Univ Helsinki, Inst Mol Med Finland FIMM, POB 20, FI-00014 Helsinki, Finland.
    Linder, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Univ Helsinki, Inst Mol Med Finland FIMM, POB 20, FI-00014 Helsinki, Finland.
    Ngasala, Billy
    Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth, Dept Med Entomol & Parasitol, Dar Es Salaam, Tanzania.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Linder, Ewert
    Univ Oulu, Ctr Microscopy & Nanotechnol, Oulu, Finland.
    Lundin, Mikael
    Univ Helsinki, Inst Mol Med Finland FIMM, POB 20, FI-00014 Helsinki, Finland.
    Moilanen, Hannu
    Univ Oulu, Ctr Microscopy & Nanotechnol, Oulu, Finland.
    Suutala, Antti
    Univ Helsinki, Inst Mol Med Finland FIMM, POB 20, FI-00014 Helsinki, Finland.
    Diwan, Vinod
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Lundin, Johan
    Univ Helsinki, Inst Mol Med Finland FIMM, POB 20, FI-00014 Helsinki, Finland.; Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium2017In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 10, no sup3, article id 1337325Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algorithms can be utilized to automate sample analysis.

    OBJECTIVE: Evaluation of the imaging performance of a miniature digital microscopy scanner for the diagnosis of soil-transmitted helminths and Schistosoma haematobium, and training of a deep learning-based image analysis algorithm for automated detection of soil-transmitted helminths in the captured images.

    METHODS: A total of 13 iodine-stained stool samples containing Ascaris lumbricoides, Trichuris trichiura and hookworm eggs and 4 urine samples containing Schistosoma haematobium were digitized using a reference whole slide-scanner and the mobile microscopy scanner. Parasites in the images were identified by visual examination and by analysis with a deep learning-based image analysis algorithm in the stool samples. Results were compared between the digital and visual analysis of the images showing helminth eggs.

    RESULTS: Parasite identification by visual analysis of digital slides captured with the mobile microscope was feasible for all analyzed parasites. Although the spatial resolution of the reference slide-scanner is higher, the resolution of the mobile microscope is sufficient for reliable identification and classification of all parasites studied. Digital image analysis of stool sample images captured with the mobile microscope showed high sensitivity for detection of all helminths studied (range of sensitivity = 83.3-100%) in the test set (n = 217) of manually labeled helminth eggs.

    CONCLUSIONS: In this proof-of-concept study, the imaging performance of a mobile, digital microscope was sufficient for visual detection of soil-transmitted helminths and Schistosoma haematobium. Furthermore, we show that deep learning-based image analysis can be utilized for the automated detection and classification of helminths in the captured images.

  • 25.
    Inoue, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Jovel, Irina
    Morris, Ulrika
    Aydin-Schmidt, Berit
    Islam, Atiqul
    Segurado, Aluisio Cotrim
    Björkman, Anders
    Di Santi, Silvia
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field Isolates Collected from the Brazilian Amazon Basin between 1984 and 20112018In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 99, no 6, p. 1504-1507Article in journal (Refereed)
    Abstract [en]

    Artemisinin resistance, presently confined to Southeast Asia and associated with mutations in the Plasmodium falciparum K13 (PfK13) propeller domain, represents a serious threat to global malaria control. This study aimed to provide baseline information for future artemisinin resistance surveillance, by analyzing the PfK13 propeller domain in P. falciparum field isolates collected from the Brazilian Amazon Basin between 1984 and 2011. A total of 152 P. falciparum mono-infections were assessed, of which 118 (78%) were collected before and 34 (22%) after the introduction of artemisinin-based combination therapy (ACT) in 2006. An 849-base pair fragment encoding the PfK13 propeller was amplified by nested PCR and sequenced in both directions. The sequences were compared with the reference sequence of P. falciparum 3D7. All samples showed wild-type sequences, thus, no mutations were observed. The results are in agreement with other recent reports and do not provide evidence for presence of PfK13 propeller domain polymorphisms associated with artemisinin resistance among P. falciparum field isolates in the Brazilian Amazon Basin neither before nor after the implementation of ACT.

  • 26.
    Inoue, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Silva, Miguel
    Fofana, Bakary
    Sanogo, Kassim
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Sagara, Issaka
    Björkman, Anders
    Veiga, Maria Isabel
    Ferreira, Pedro Eduardo
    Djimde, Abdoulaye
    Gil, José Pedro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Plasmodium falciparum Plasmepsin 2 Duplications, West Africa2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 8, p. 1591-1593Article in journal (Refereed)
    Abstract [en]

    Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as antimalaria drug in Africa. We report the detection in Mali of Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the long-term efficacy of DHA/PPQ treatment in Africa.

  • 27.
    Ishengoma, Deus S.
    et al.
    Natl Inst Med Res, Tanga Res Ctr, Tanga, Tanzania.
    Mandara, Celine I.
    Natl Inst Med Res, Tanga Res Ctr, Tanga, Tanzania;Kilimanjaro Christian Med Univ Coll, Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
    Francis, Filbert
    Natl Inst Med Res, Tanga Res Ctr, Tanga, Tanzania.
    Talundzic, Eldin
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Lucchi, Naomi W.
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Sch Publ Hlth, Dar Es Salaam, Tanzania.
    Kabanywanyi, Abdunoor M.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
    Mahende, Muhidin K.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
    Kamugisha, Erasmus
    Catholic Univ Hlth & Allied Sci, Bugando Med Ctr, Mwanza, Tanzania.
    Kavishe, Reginald A.
    Kilimanjaro Christian Med Univ Coll, Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
    Muro, Florida
    Kilimanjaro Christian Med Univ Coll, Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
    Mohamed, Ally
    Natl Malaria Control Programme, Ocean Rd Luthuli Ave NIMR Complex, Dar Es Salaam, Tanzania.
    Mandike, Renata
    Natl Malaria Control Programme, Ocean Rd Luthuli Ave NIMR Complex, Dar Es Salaam, Tanzania.
    Mkude, Sigsbert
    Natl Malaria Control Programme, Ocean Rd Luthuli Ave NIMR Complex, Dar Es Salaam, Tanzania.
    Chacky, Frank
    Natl Malaria Control Programme, Ocean Rd Luthuli Ave NIMR Complex, Dar Es Salaam, Tanzania.
    Paxton, Lynn
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Greer, George
    US Embassy, US Presidents Malaria Initiat, US Agcy Int Dev, Dar Es Salaam, Tanzania.
    Kitojo, Chonge A.
    US Embassy, US Presidents Malaria Initiat, US Agcy Int Dev, Dar Es Salaam, Tanzania.
    Njau, Ritha
    WHO, Country Off, Dar Es Salaam, Tanzania.
    Martin, Troy
    Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, 1124 Columbia St, Seattle, WA 98104 USA.
    Venkatesan, Meera
    US Agcy Int Dev, US Presidents Malaria Initiat, Washington, DC 20523 USA.
    Warsame, Marian
    WHO, Global Malaria Programme, 20 Ave Appia, CH-1211 Geneva 27, Switzerland;Gothenburg Univ, Gothenburg, Sweden.
    Halsey, Eric S.
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Atlanta, GA USA;Ctr Dis Control & Prevent, US Presidents Malaria Initiat, Atlanta, GA USA.
    Udhayakumar, Venkatachalam
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania2019In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 18, article id 88Article in journal (Refereed)
    Abstract [en]

    Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance.

    Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively.

    Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene.

    Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies.

  • 28.
    Jones, Clarer
    et al.
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, POB 65011, Dar Es Salaam, Tanzania.
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, POB 65011, Dar Es Salaam, Tanzania.
    Derua, Yahya A.
    Natl Inst Med Res, POB 9653, Dar Es Salaam, Tanzania.
    Tarimo, Donath
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, POB 65011, Dar Es Salaam, Tanzania.
    Reimer, Lisa
    Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England.
    Bockarie, Moses
    European & Dev Countries Clin Trials Partnership, Cape Town, South Africa.
    Malecela, Mwelecele N.
    WHO Reg Off Africa, Brazzaville, Rep Congo.
    Lymphatic filariasis transmission in Rufiji District, southeastern Tanzania: infection status of the human population and mosquito vectors after twelve rounds of mass drug administration2018In: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 11, article id 588Article in journal (Refereed)
    Abstract [en]

    BackgroundControl of lymphatic filariasis (LF) in most of the sub-Saharan African countries is based on annual mass drug administration (MDA) using a combination of ivermectin and albendazole. Monitoring the impact of this intervention is crucial for measuring the success of the LF elimination programmes. This study assessed the status of LF infection in Rufiji district, southeastern Tanzania after twelve rounds of MDA.MethodsCommunity members aged between 10 and 79 years were examined for Wuchereria bancrofti circulating filarial antigens (CFA) using immunochromatographic test cards (ICTs) and antigen-positive individuals were screened for microfilaraemia. All study participants were examined for clinical manifestation of LF and interviewed for drug uptake during MDA rounds. Filarial mosquito vectors were collected indoor and outdoor and examined for infection with W. bancrofti using a microscope and quantitative real-time polymerase chain reaction (qPCR) techniques.ResultsOut of 854 participants tested, nine (1.1%) were positive for CFA and one (0.1%) was found to be microfilaraemic. The prevalence of hydrocele and elephantiasis was 4.8% and 2.9%, respectively. Surveyed drug uptake rates were high, with 70.5% of the respondents reporting having swallowed the drugs in the 2014 MDA round (about seven months before this study). Further, 82.7% of the respondents reported having swallowed the drugs at least once since the inception of MDA programme in 2000. Of the 1054 filarial vectors caught indoors and dissected to detect W. bancrofti infection none was found to be infected. Moreover, analysis by qPCR of 1092 pools of gravid Culex quinquefasciatus collected outdoors resulted in an estimated infection rate of 0.1%. None of the filarial vectors tested with qPCR were found to be infective.ConclusionAnalysis of indices of LF infection in the human population and filarial mosquito vectors indicated a substantial decline in the prevalence of LF and other transmission indices, suggesting that local transmission was extremely low if occurring at all in the study areas. We, therefore, recommend a formal transmission assessment survey (TAS) to be conducted in the study areas to make an informed decision on whether Rufiji District satisfied WHO criteria for stopping MDA.

  • 29.
    Kallioinen, Maija
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Khan, Ashraful Islam
    Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh.
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Rahman, Anisur
    Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 12, p. 1979-1986Article in journal (Refereed)
    Abstract [en]

    AIM: A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity.

    METHODS: This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 μg folic acid, 30 mg iron with 400 μg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity.

    RESULTS: There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months.

    CONCLUSION: Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

  • 30.
    KC, Ashish
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Health Section, United Nations Children’s Fund (UNICEF), Lalitpur, Nepal; Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal.
    Rana, Nisha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Jarawka Ranneberg, Linda
    epartment of Pediatrics, Hospital of Halland, Halmstad, Sweden.
    Subedi, Kalpana
    Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal.
    Andersson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Effects of Delayed Umbilical Cord Clamping vs Early Clamping on Anemia in Infants at 8 and 12 Months: A Randomized Clinical Trial2017In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, no 3, p. 264-270Article in journal (Refereed)
    Abstract [en]

    Importance: Delayed umbilical cord clamping has been shown to improve iron stores in infants to 6 months of age. However, delayed cord clamping has not been shown to prevent iron deficiency or anemia after 6 months of age.

    Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on hemoglobin and ferritin levels at 8 and 12 months of age in infants at high risk for iron deficiency anemia.

    Design, Setting, and Participants: This randomized clinical trial included 540 late preterm and term infants born vaginally at a tertiary hospital in Kathmandu, Nepal, from October 2 to November 21, 2014. Follow-up included blood levels of hemoglobin and ferritin at 8 and 12 months of age. Follow-up was completed on December 11, 2015. Analysis was based on intention to treat.

    Interventions: Infants were randomized to delayed umbilical cord clamping (≥180 seconds after delivery) or early clamping (≤60 seconds after delivery).

    Main Outcomes and Measures: Main outcomes included hemoglobin and anemia levels at 8 months of age with the power estimate based on the prevalence of anemia. Secondary outcomes included hemoglobin and anemia levels at 12 months of age and ferritin level, iron deficiency, and iron deficiency anemia at 8 and 12 months of age.

    Results: In this study of 540 infants (281 boys [52.0%] and 259 girls [48.0%]; mean [SD] gestational age, 39.2 [1.1] weeks), 270 each were randomized to the delayed and early clamping groups. At 8 months of age, 212 infants (78.5%) from the delayed group and 188 (69.6%) from the early clamping group returned for blood sampling. After multiple imputation analysis, infants undergoing delayed clamping had higher levels of hemoglobin (10.4 vs 10.2 g/dL; difference, 0.2 g/dL; 95% CI, 0.1 to 0.4 g/dL). Delayed cord clamping also reduced the prevalence of anemia (hemoglobin level <11.0 g/dL) at 8 months in 197 (73.0%) vs 222 (82.2%) infants (relative risk, 0.89; 95% CI, 0.81-0.98; number needed to treat [NNT], 11; 95% CI, 6-54). At 8 months, the risk for iron deficiency was reduced in the delayed clamping group in 60 (22.2%) vs 103 (38.1%) patients (relative risk, 0.58; 95% CI, 0.44-0.77; NNT, 6; 95% CI, 4-13). At 12 months, delayed cord clamping still resulted in a hemoglobin level of 0.3 (95% CI, 0.04-0.5) g/dL higher than in the early cord clamping group and a relative risk for anemia of 0.91 (95% CI, 0.84-0.98), resulting in a NNT of 12 (95% CI, 7-78).

    Conclusions and Relevance: Delayed cord clamping reduces anemia at 8 and 12 months of age in a high-risk population, which may have major positive effects on infants' health and development.

    Trial Registration: clinicaltrials.gov Identifier: NCT02222805.

  • 31.
    KC, Ashish
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Health Section, UNICEF, UN House, Lalitpur, Nepal.
    Bergström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Institute for Global Health, University College London, London, UK.
    Chaulagain, Dipak
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Lifeline Nepal, Kathmandu, Nepal.
    Brunell, Olivia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Gurung, Abhishek
    Lifeline Nepal, Kathmandu, Nepal.
    Eriksson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Litorp, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Maternal and Reproductive Health and Migration.
    Wrammert, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Grönqvist, Erik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Edin, Per-Anders
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Le Grange, Claire
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Lamichhane, Bikash
    Department of Health Services, Ministry of Health, Nepal.
    Shrestha, Parashuram
    Department of Health Services, Ministry of Health, Nepal.
    Pokharel, Amrit
    Department of Health Services, Ministry of Health, Nepal.
    Pun, Asha
    Health Section, UNICEF, UN House, Lalitpur, Nepal.
    Singh, Chahana
    Health Section, UNICEF, UN House, Lalitpur, Nepal .
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Scaling up quality improvement intervention for perinatal care in Nepal (NePeriQIP); study protocol of a cluster randomised trial2017In: BMJ global health, Vol. 2, no 3, article id e000497Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to scale up a quality improvement (QI) intervention for perinatal care according to WHO/National guidelines in hospitals of Nepal using the existing health system structures. The intervention builds on previous research on the implementation of Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting in Nepal. The objective of this study is to evaluate the effect of this scaled-up intervention on perinatal health outcomes.

    METHODS/DESIGN: Cluster-randomised controlled trial using a stepped wedged design with 3 months delay between wedges will be conducted in 12 public hospitals with a total annual delivery rate of 60 000. Each wedge will consist of 3 hospitals. Impact will be evaluated on intrapartum-related mortality (primary outcome), overall neonatal mortality and morbidity and health worker's performance on neonatal care (secondary outcomes). A process evaluation and a cost-effectiveness analysis will be performed to understand the functionality of the intervention and to further guide health system investments will also be performed.

    DISCUSSION: In contexts where resources are limited, there is a need to find scalable and sustainable implementation strategies for improved care delivery. The proposed study will add to the scarce evidence base on how to scale up interventions within existing health systems. If successful, the NePeriQIP model can provide a replicable solution in similar settings where support and investment from the health system is poor, and national governments have made a global pledge to reduce perinatal mortality.

    TRIAL REGISTRATION NUMBER: ISRCTN30829654.

  • 32.
    Kitutu, Freddy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Chrispus, Mayora
    Johansson, Emily White
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Wamani, Henry
    Bigdeli, Maryam
    Shroff, Zubin Cyrus
    Health system effects of implementing integrated community case management (iCCM) intervention in private retail drug shops in South Western Uganda: a qualitative study2017In: BMJ Global Health, ISSN 2059-7908, Vol. 2, no e000334Article in journal (Refereed)
    Abstract [en]

    Background Intervening in private drug shops to improve quality of care and enhance regulatory oversight may have health system effects that need to be understood before scaling up any such interventions. We examine the processes through which a drug shop intervention culminated in positive unintended effects and other dynamic interactions within the underlying health system.

    Methods A multifaceted intervention consisting of drug seller training, supply of diagnostics and subsidised medicines, use of treatment algorithms, monthly supervision and community sensitisation was implemented in drug shops in South Western Uganda, to improve paediatric fever management. Focus group discussions and in-depth interviews were conducted with stakeholders (drug sellers, government officials and community health workers) at baseline, midpoint and end-line between September 2013 and September 2015. Using a health market and systems lens, transcripts from the interviews were analysed to identify health system effects associated with the apparent success of the intervention.

    Findings Stakeholders initially expressed caution and fears about the intervention's implications for quality, equity and interface with the regulatory framework. Over time, these stakeholders embraced the intervention. Most respondents noted that the intervention had improved drug shop standards, enabled drug shops to embrace patient record keeping, parasite-based treatment of malaria and appropriate medicine use. There was also improved supportive supervision, and better compliance to licensing and other regulatory requirements. Drug seller legitimacy was enhanced from the community and client perspective, leading to improved trust in drug shops.

    Conclusion The study showed how effectively using health technologies and the perceived efficacy of medicines contributed to improved legitimacy and trust in drug shops among stakeholders. The study also demonstrated that using a combination of appropriate incentives and consumer empowerment strategies can help harmonise common practices with medicine regulations and safeguard public health, especially in mixed health market contexts.

  • 33.
    Kitutu, Freddy Eric
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Kalyango, Joan Nakayaga
    Mayora, Chrispus
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Wamani, Henry
    Integrated community case management by drug sellers influences appropriate treatment of paediatric febrile illness in South Western Uganda: a quasi-experimental study.2017In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, no 1, article id 425Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fever case management is a major challenge for improved child health globally, despite existence of cheap and effective child survival health technologies. The integrated Community Case Management (iCCM) intervention of paediatric febrile illnesses though adopted by Uganda's Ministry of Health to be implemented by community health workers, has not addressed the inaccess to life-saving medicines and diagnostics. Therefore, the iCCM intervention was implemented in private drug shops and evaluated for its effect on appropriate treatment of paediatric fever in a low malaria transmission setting in South Western Uganda.

    METHODS: From June 2013 to September 2015, the effect of the iCCM intervention on drug seller paediatric fever management and adherence to iCCM guidelines was assessed in a quasi-experimental study in South Western Uganda. A total of 212 care-seeker exit interviews were done before and 285 after in the intervention arm as compared to 216 before and 268 care-seeker interviews at the end of the study period in the comparison arm. The intervention effect was assessed by difference-in-difference analysis of drug seller treatment practices against national treatment recommendations between the intervention and comparison arms. Observed proportions among care-seeker interviews were compared with corresponding proportions from 5795 child visits recorded in patient registries and 49 direct observations of drug seller-care-seeker encounters in intervention drug shops.

    RESULTS: The iCCM intervention increased the appropriate treatment of uncomplicated malaria, pneumonia symptoms and non-bloody diarrhoea by 80.2% (95% CI 53.2-107.2), 65.5% (95% CI 51.6-79.4) and 31.4% (95% CI 1.6-61.2), respectively. Within the intervention arm, drug seller scores on appropriate treatment for pneumonia symptoms and diagnostic test use were the same among care-seeker exit interviews and direct observation. A linear trend (negative slope, - 0.009 p value < 0.001) was observed for proportions of child cases prescribed any antimicrobial medicine in the intervention arm drug shops.

    CONCLUSIONS: The iCCM intervention improved appropriate treatment for uncomplicated malaria, pneumonia symptoms and diarrhoea. Drug seller adherence to iCCM guidelines was high, without causing excessive prescription of antimicrobial medicines in this study. Further research should assess whether this effect is sustained over time and under routine supervision models.

  • 34.
    Kitutu, Freddy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Martensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Wamani, Henry
    Makerere University School of Public Health.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Kalyango, Joan
    Makerere University College of Health Sciences, Department of Pharmacy.
    Perceived quality of paediatric fever care from private drug shops and care-seeking choice in South Western Uganda: data from household surveys.In: Article in journal (Refereed)
    Abstract [en]

    Background

    Child mortality is influenced by interventions beyond the health sector such as adequate access to education, quality water and sanitation, transport and general socio-economic wellbeing. Child mortality due to febrile illnesses remains unevenly distributed within countries. The role of context and variables that act at a higher level such as a geographical location has been largely under-examined. Factors that act at group level are commonly described in literature as neighbourhood factors. The aim of the study was to investigate whether contextual differences in choice of childhood fever care-seeking in South Western Uganda remain after relevant individual and household characteristics have been taken into account, for three outcome variables, namely, choice of care-seeking in private versus government health facilities, choice of care-seeking in private health facilities versus community level and perceived quality of childhood fever care at drug shops, among households in Mbarara and Bushenyi districts.

    Methods

    Two household surveys were conducted at different time periods in Bushenyi and Mbarara districts. The first survey of 2261 households was conducted from July to October 2013 before implementation of an adapted integrated Community Case Management (iCCM) intervention for paediatric febrile illness in drug shops in Mbarara district. The second survey of 3073 households was done from April to May 2015 after the intervention. These data were analysed for effect of contextual factors, the iCCM intervention and other predictors on choice of care-seeking and perceived quality of care among the households in Mbarara and Bushenyi.

     

    Results:

    In the pre-intervention survey , more households in both Mbarara and Bushenyi reported time required to travel to either a private clinic (31%) or drug shop (43%) of 15 minutes or less as compared to a government health facility (12%). The crude second level (neighbourhood) variance of the odds ratio for care-seeking in private versus government health facility was 0.446 (SE, 0.089). The intra-neighbourhood correlation and median odds ratio were 11.9% and 1.89, respectively, for the crude model. After adjusting for covariates that were kept in the prediction model, the estimates of neighbourhood variance, intra-neighbourhood correlation and mean odds ratio decreased to 0.241 (0.069), 6.8% and 1.6, respectively.

     

    Conclusion:         

    In addition to individual factors, contextual characteristics of the neighbourhoods predict the choice of care-seeking from private versus government health facilities, private health facilities versus in the community and perceived quality of pediatric fever care at drug shops.

  • 35.
    Kitutu, Freddy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Makerere Univ, Coll Hlth Sci, Pharm Dept, Kampala, Uganda.
    Wamani, Henry
    Makerere University School of Public Health.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Katabazi, Fred
    Makerere University College of Health Sciences, Department of Medical Microbiology.
    Kuteesa, Ronald
    Makerere University College of Health Sciences, Infectious Disease Institute.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Makerere Univ, Coll Hlth Sci, Pharm Dept, Kampala, Uganda; Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda.
    Kalyango, Joan
    Makerere University College of Health Sciences, Department of Pharmacy.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Can malaria rapid diagnostic tests by drug sellers under feld conditions classify children 5 years old or less with or without Plasmodium falciparum malaria?: Comparison with nested PCR analysis2018In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, article id 365Article in journal (Refereed)
    Abstract [en]

    Background

    Malaria rapid diagnostic tests (RDTs) available as dipsticks or strips, are simple to perform, easily interpretable and do not require electricity nor infrastructural investment. Correct interpretation of and compliance with the malaria RDT results is a challenge to drug sellers. Thus, drug seller interpretation of malaria RDT strips was compared with laboratory scientist re-reading, and PCR analysis of Plasmodium DNA extracted from malaria RDT nitrocellulose strips and Fast Transient Analysis (FTA) cards. Malaria RDT cassettes are also assessed as potential source of Plasmodium DNA.

    Methods

    A total of 212 children aged between 2 and 60 months, 199 of whom had complete records at two study drug shops in south west Uganda participated in the study. Duplicate 5μL samples of capillary blood were picked from the 212 children, dispensed onto the sample well of the CareStartTM Pf-HRP2 RDT cassette and a fast transient analysis (FTA), WhatmanTM 3MM filter paper in parallel. The malaria RDT strip was interpreted by the drug seller within 15 to 20 minutes, visually re-read centrally by laboratory scientist and from it; Plasmodium DNA was recovered and detected by PCR, and compared with FTA recovered P. falciparum DNA PCR detection.

    Results

    Malaria positive samples were 62/199 (31.2% 95% CI 24.9 - 38.3) by drug seller interpretation of malaria RDT strip, 59/212 (27.8% 95% CI 22.2 – 34.3) by laboratory scientist, 55/212 (25.9% 95% CI 20.0 – 32.6) by RDT nitrocellulose strip PCR and 64/212 (30.2% 95% CI 24.4 – 37.7). The overall agreement between the drug seller interpretation and laboratory scientist re-reading of the malaria RDT strip was 93% with kappa value of 0.8 (95 % CI 0.7, 0.9). The drug seller compliance with the reported malaria RDT results and kappa value were 92.5% and 0.8 (95% CI 0.7, 0.9), respectively. The performance of the three diagnostic strategies compared with FTA PCR as the gold standard had sensitivity between 76.6% and 86.9%, specificity above 90%, positive predictive value ranging from 79% to 89.8% and negative predictive value above 90%.

    Conclusion:

    Drug sellers can use of malaria RDTs in field conditions and achieve acceptable accuracy for malaria diagnosis, and they comply with the malaria RDT results. Plasmodium DNA can be recovered from malaria RDT nitrocellulose strips even in the context of drug shops. Future malaria surveillance and diagnostic quality control studies with malaria RDT cassette as a source of Plasmodium DNA are recommended.

  • 36. Kloprogge, Frank
    et al.
    Workman, Lesley
    Borrmann, Steffen
    Tékété, Mamadou
    Lefèvre, Gilbert
    Hamed, Kamal
    Piola, Patrice
    Ursing, Johan
    Kofoed, Poul Erik
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Ngasala, Billy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Björkman, Anders
    Ashton, Michael
    Friberg Hietala, Sofia
    Aweeka, Francesca
    Parikh, Sunil
    Mwai, Leah
    Davis, Timothy M E
    Karunajeewa, Harin
    Salman, Sam
    Checchi, Francesco
    Fogg, Carole
    Newton, Paul N
    Mayxay, Mayfong
    Deloron, Philippe
    Faucher, Jean François
    Nosten, François
    Ashley, Elizabeth A
    McGready, Rose
    van Vugt, Michele
    Proux, Stephane
    Price, Ric N
    Karbwang, Juntra
    Ezzet, Farkad
    Bakshi, Rajesh
    Stepniewska, Kasia
    White, Nicholas J
    Guerin, Philippe J
    Barnes, Karen I
    Tarning, Joel
    Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.2018In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, no 6, article id e1002579Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations.

    METHODS AND FINDINGS: A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing <15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7.

    CONCLUSIONS: Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.

  • 37.
    Lawn, Joy E
    et al.
    London Sch Hyg & Trop Med, Maternal Adolescent & Reprod Hlth MARCH Ctr, Keppel St, London WC1E 7HT, England.
    Bhutta, Zulfiqar A
    Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan.; Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada.
    Wall, Steve N
    Saving Newborn Lives, Save the Children, Washington, DC, USA.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. UNICEF, New York, NY, USA.; Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa.
    Daviaud, Emmanuelle
    Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa.
    Cadres, content and costs for community-based care for mothers and newborns from seven countries: implications for universal health coverage2017In: Health Policy and Planning, ISSN 0268-1080, E-ISSN 1460-2237, Vol. 32, no suppl_1, p. i1-i5Article in journal (Other academic)
  • 38.
    Linder, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland .
    Taylor, Jenny C
    Wellcome Trust Centre for Human Genetics, University of Oxford and Oxford NIHR Biomedical Research Centre, Oxford, UK .
    Colling, Richard
    Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK .
    Pell, Robert
    Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK .
    Alveyn, Edward
    University of Oxford, Medical School, Oxford, UK .
    Joseph, Johnson
    Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
    Protheroe, Andrew
    Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
    Lundin, Mikael
    Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland.
    Lundin, Johan
    Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland; Department of Public Health Sciences, Global Health/IHCAR, Karolinska Institutet, Stockholm, Sweden.
    Verrill, Clare
    Nuffield Department of Surgical Sciences and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK .
    Deep learning for detecting tumour-infiltrating lymphocytes in testicular germ cell tumours2018In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 72, no 2, p. 157-164Article in journal (Refereed)
    Abstract [en]

    AIMS: To evaluate if a deep learning algorithm can be trained to identify tumour-infiltrating lymphocytes (TILs) in tissue samples of testicular germ cell tumours and to assess whether the TIL counts correlate with relapse status of the patient.

    METHODS: TILs were manually annotated in 259 tumour regions from 28 whole-slide images (WSIs) of H&E-stained tissue samples. A deep learning algorithm was trained on half of the regions and tested on the other half. The algorithm was further applied to larger areas of tumour WSIs from 89 patients and correlated with clinicopathological data.

    RESULTS: A correlation coefficient of 0.89 was achieved when comparing the algorithm with the manual TIL count in the test set of images in which TILs were present (n=47). In the WSI regions from the 89 patient samples, the median TIL density was 1009/mm2. In seminomas, none of the relapsed patients belonged to the highest TIL density tertile (>2011/mm2). TIL quantifications performed visually by three pathologists on the same tumours were not significantly associated with outcome. The average interobserver agreement between the pathologists when assigning a patient into TIL tertiles was 0.32 (Kappa test) compared with 0.35 between the algorithm and the experts, respectively. A higher TIL density was associated with a lower clinical tumour stage, seminoma histology and lack of lymphovascular invasion.

    CONCLUSIONS: Deep learning-based image analysis can be used for detecting TILs in testicular germ cell cancer more objectively and it has potential for use as a prognostic marker for disease relapse.