General ward nurses detection and response to clinical deterioration in three hospitals at the Kenyan coast: a convergent parallel mixed methods study.

BACKGROUND: In low and middle-income countries like Kenya, critical care facilities are limited, meaning acutely ill patients are managed in the general wards. Nurses in these wards are expected to detect and respond to patient deterioration to prevent cardiac arrest or death. This study examined nurses' vital signs documentation practices during clinical deterioration and explored factors influencing their ability to detect and respond to deterioration. METHODS: This convergent parallel mixed methods study was conducted in the general medical and surgical wards of three hospitals in Kenya's coastal region. Quantitative data on the extent to which the nurses monitored and documented the vital signs 24 h before a cardiac arrest (death) occurred was retrieved from patients' medical records. In-depth, semi-structured interviews were conducted with twenty-four purposefully drawn registered nurses working in the three hospitals' adult medical and surgical wards. RESULTS: This study reviewed 405 patient records and found most of the documentation of the vital signs was done in the nursing notes and not the vital signs observation chart. During the 24 h prior to death, respiratory rate was documented the least in only 1.2% of the records. Only a very small percentage of patients had any vital event documented for all six-time points, i.e. four hourly. Thematic analysis of the interview data identified five broad themes related to detecting and responding promptly to deterioration. These were insufficient monitoring of vital signs linked to limited availability of equipment and supplies, staffing conditions and workload, lack of training and guidelines, and communication and teamwork constraints among healthcare workers. CONCLUSION: The study showed that nurses did not consistently monitor and record vital signs in the general wards. They also worked in suboptimal ward environments that do not support their ability to promptly detect and respond to clinical deterioration. The findings illustrate the importance of implementation of standardised systems for patient assessment and alert mechanisms for deterioration response. Furthermore, creating a supportive work environment is imperative in empowering nurses to identify and respond to patient deterioration. Addressing these issues is not only beneficial for the nurses but, more importantly, for the well-being of the patients they serve.

Not just surveys and indicators: narratives capture what really matters for health system strengthening.

Health system strengthening remains elusive and challenging. Health systems in many countries in sub-Saharan Africa are frequently characterised as weak, with inadequate management and accountability mechanisms, and poor human and financial resources. Putting patients and staff at the heart of health systems is an essential step towards strengthening them. As one of the three pillars of quality in health care, understanding patient experiences is key to moving towards people-centred care. Yet patient experiences are not a singular concept. Patient narratives can convey individual experiences of illness and health care, which complement and augment epidemiological and public health evidence. These narratives, gathered with rigorous, interview-based research and shared with digital tools (audio and video), can generate persuasive evidence. This evidence has important potential for influencing policy and practice, and for supporting people-centred care, but has not been tested systematically in low-income countries. In the Kenyan context of newborn health, work under way is generating evidence to show the transformative potential of patient narratives.

The hidden emotional labour behind ensuring the social value of research: Experiences of frontline health policy and systems researchers based in Kenya during COVID-19.

Health policy and systems research (HPSR) is a multi-disciplinary, largely applied field of research aimed at understanding and strengthening the performance of health systems, often with an emphasis on power, policy and equity. The value of embedded and participatory HPSR specifically in facilitating the collection of rich data that is relevant to addressing real-world challenges is increasingly recognised. However, the potential contributions and challenges of HPSR in the context of shocks and crises are not well documented, with a particular gap in the literature being the experiences and coping strategies of the HPSR researchers who are embedded in health systems in resource constrained settings. In this paper, we draw on two sets of group discussions held among a group of approximately 15 HPSR researchers based in Nairobi, Kenya, who were conducting a range of embedded HPSR studies throughout the COVID-19 pandemic. The researchers, including many of the authors, were employed by the KEMRI-Wellcome Trust Research Programme (KWTRP), which is a long-standing multi-disciplinary partnership between the Kenya Medical Research Institute and the Wellcome Trust with a central goal of contributing to national and international health policy and practice. We share our findings in relation to three inter-related themes: 1) Ensuring the continued social value of our HPSR work in the face of changing priorities; 2) Responding to shifting ethical procedures and processes at institutional and national levels; and 3) Protecting our own and front-line colleagues' well-being, including clinical colleagues. Our experiences highlight that in navigating research work and responsibilities to colleagues, patients and participants through the pandemic, many embedded HPSR staff faced difficult emotional and ethical challenges, including heightened forms of moral distress, which may have been better prevented and supported. We draw on our findings and the wider literature to discuss considerations for funders and research leads with an eye to strengthening support for embedded HPSR staff, not only in crises such as the on-going COVID-19 pandemic, but also more generally.

A long-term observational study of paediatric snakebite in Kilifi County, south-east Kenya.

INTRODUCTION: Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. METHODS: All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. RESULTS: Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6-12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. CONCLUSION: There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication.

Design and implementation of a community-based mother-to-mother peer support programme for the follow-up of low birthweight infants in rural western Kenya.

Background: Globally, low birthweight (LBW) infants (<2,500 g) have the highest risk of mortality during the first year of life. Those who survive often have adverse health outcomes. Post-discharge outcomes of LBW infants in impoverished communities in Africa are largely unknown. This paper describes the design and implementation of a mother-to-mother peer training and mentoring programme for the follow-up of LBW infants in rural Kenya. Methods: Key informant interviews were conducted with 10 mothers of neonates (infants <28 days) from two rural communities in western Kenya. These data informed the identification of key characteristics required for mother-to-mother peer supporters (peer mothers) following up LBW infants post discharge. Forty potential peer mothers were invited to attend a 5-day training programme that focused on three main themes: supportive care using appropriate communication, identification of severe illness, and recommended care strategies for LBW infants. Sixteen peer mothers were mentored to conduct seven community follow-up visits to each mother-LBW infant pair with fifteen completing all the visits over a 6-month period. A mixed methods approach was used to evaluate the implementation of the programme. Quantitative data of peer mother socio-demographic characteristics, recruitment, and retention was collected. Two post-training focus group discussions were conducted with the peer mothers to explore their experiences of the programme. Descriptive statistics were generated from the quantitative data and the qualitative data was analysed using a thematic framework. Results: The median age of the peer mothers was 26 years (range 21-43). From March-August 2019, each peer mother conducted a median of 28 visits (range 7-77) with fourteen (88%) completing all their assigned follow-up visits. Post training, our interviews suggest that peer mothers felt empowered to promote appropriate infant feeding practices. They gave multiple examples of improved health seeking behaviours as a result of the peer mother training programme. Conclusion: Our peer mother training programme equipped peer mothers with the knowledge and skills for the post-discharge follow-up of LBW infants in this rural community in Kenya. Community-based interventions for LBW infants, delivered by appropriately trained peer mothers, have the potential to address the current gaps in post-discharge care for these infants.

Protocol for the Pathways Study: a realist evaluation of staff social ties and communication in the delivery of neonatal care in Kenya.

INTRODUCTION: The informal social ties that health workers form with their colleagues influence knowledge, skills and individual and group behaviours and norms in the workplace. However, improved understanding of these 'software' aspects of the workforce (eg, relationships, norms, power) have been neglected in health systems research. In Kenya, neonatal mortality has lagged despite reductions in other age groups under 5 years. A rich understanding of workforce social ties is likely to be valuable to inform behavioural change initiatives seeking to improve quality of neonatal healthcare.This study aims to better understand the relational components among health workers in Kenyan neonatal care areas, and how such understanding might inform the design and implementation of quality improvement interventions targeting health workers' behaviours. METHODS AND ANALYSIS: We will collect data in two phases. In phase 1, we will conduct non-participant observation of hospital staff during patient care and hospital meetings, a social network questionnaire with staff, in-depth interviews, key informant interviews and focus group discussions at two large public hospitals in Kenya. Data will be collected purposively and analysed using realist evaluation, interim analyses including thematic analysis of qualitative data and quantitative analysis of social network metrics. In phase 2, a stakeholder workshop will be held to discuss and refine phase one findings.Study findings will help refine an evolving programme theory with recommendations used to develop theory-informed interventions targeted at enhancing quality improvement efforts in Kenyan hospitals. ETHICS AND DISSEMINATION: The study has been approved by Kenya Medical Research Institute (KEMRI/SERU/CGMR-C/241/4374) and Oxford Tropical Research Ethics Committee (OxTREC 519-22). Research findings will be shared with the sites, and disseminated in seminars, conferences and published in open-access scientific journals.

Keeping It Real: Antibiotic Use Problems and Stewardship Solutions in Low- and Middle-income Countries.

Antimicrobial resistance is a global health threat and there is an urgent need to manage antibiotic use to slow its development. However, antimicrobial stewardship interventions in low- and middle-income countries (LMIC) have been limited in terms of their resourcing, feasibility and effectiveness in the face of greater challenges in child mortality. We sought to gather together examples of antibiotic use problems faced by clinicians in LMIC, many of which are unique to these settings, and real-world antimicrobial stewardship solutions identified, with the goal of learning broader lessons that might be applicable across LMIC.

Strengthening respectful communication with patients and colleagues in neonatal units - developing and evaluating a communication and emotional competence training for nurse managers in Kenya.

Introduction: Effective communication is essential to delivering compassionate, high-quality nursing care. The intensive, stressful and technical environment of a new-born unit (NBU) in a low-resource setting presents communication-related challenges for nurses, with negative implications for nurse well-being, team relationships and patient care. We adapted a pre-existing communication and emotional competence course with NBU nurse managers working in Kenya, explored its' value to participants and developed a theory of change to evaluate its' potential impact. Methods: 18 neonatal nurse managers from 14 county referral hospitals helped adapt and participated in a nine-month participatory training process. Training involved guided 'on the job' self-observation and reflection to build self-awareness, and two face-to-face skills-building workshops. The course and potential for future scale up was assessed using written responses from participant nurses (baseline questionnaires, reflective assignments, pre and post workshop questionnaires), workshop observation notes, two group discussions and nine individual in-depth interviews. Results: Participants were extremely positive about the course, with many emphasizing its direct relevance and applicability to their daily work. Increased self-awareness and ability to recognize their own, colleagues' and patients' emotional triggers, together with new knowledge and practical skills, reportedly inspired nurses to change; in turn influencing their ability to provide respectful care, improving their confidence and relationships and giving them a stronger sense of professional identity. Conclusion: Providing respectful care is a major challenge in low-resource, high-pressure clinical settings but there are few strategies to address this problem. The participatory training process examined addresses this challenge and has potential for positive impacts for families, individual workers and teams, including worker well-being. We present an initial theory of change to support future evaluations aimed at exploring if and how positive gains can be sustained and spread within the wider system.

Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial.

BACKGROUND: Triple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children. METHODS: In this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2-12 years and had an asexual parasitaemia of 5000-250 000 parasites per µL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane-piperaquine, arterolane-piperaquine-mefloquine, or artemether-lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether-lumefantrine was administered twice daily (target dose 5-24 mg/kg of bodyweight of artemether and 29-144 mg/kg of bodyweight of lumefantrine), and oral arterolane-piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane-piperaquine-mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane-piperaquine-mefloquine versus artemether-lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane-piperaquine-mefloquine versus arterolane-piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was -7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed. FINDINGS: Between March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane-piperaquine (n=73), arterolane-piperaquine-mefloquine (n=72), or artemether-lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane-piperaquine-mefloquine (100%, 95% CI 95-100; 72/72) was non-inferior to that after treatment with artemether-lumefantrine (96%, 95% CI 88-99; 69/72; risk difference 4%, 95% CI 0-9; p=0·25). The 42-day PCR-corrected efficacy of arterolane-piperaquine-mefloquine was non-inferior to that of arterolane-piperaquine (100%, 95% CI 95-100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane-piperaquine (5%, 95% CI 2-9; ten of 203 drug administrations; p=0·0013) or arterolane-piperaquine-mefloquine (5%, 3-9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether-lumefantrine (1%, 0-2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether-lumefantrine; n=19 for arterolane-piperaquine-mefloquine; n=23 for arterolane-piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths. INTERPRETATION: This study shows that arterolane-piperaquine-mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance. FUNDING: UK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries.

An innovative leadership development initiative to support building everyday resilience in health systems.

Effective management and leadership are essential for everyday health system resilience, but actors charged with these roles are often underprepared and undersupported to perform them. Particular challenges have been observed in interpersonal and relational aspects of health managers' work, including communication skills, emotional competence and supportive oversight. Within the Resilient and Responsive Health Systems (RESYST) consortium in Kenya, we worked with two county health and hospital management teams to adapt a package of leadership development interventions aimed at building these skills. This article provides insights into: (1) the content and co-development of a participatory intervention combining two core elements: a complex health system taught course, and an adapted communications and emotional competence process training; and (2) the findings from a formative evaluation of this intervention which included observations of the training, individual interviews with participating managers and discussions in regular meetings with managers. Following the training, managers reported greater recognition of the importance of health system software (values, belief systems and relationships), and improved self-awareness and team communication. Managers appeared to build valued skills in active listening, giving constructive feedback, 'stepping back' from automatic reactions to challenging emotional situations and taking responsibility to communicate with emotional competence. The training also created spaces for managers to share experiences, reflect upon and nurture social competences. We draw on our findings and the literature to propose a theory of change regarding the potential of our leadership development intervention to nurture everyday health system resilience through strengthening cognitive, behavioural and contextual capacities. We recommend further development and evaluation of novel approaches such as those shared in this article to support leadership development and management in complex, hierarchical systems.

Tools for measuring medical internship experience: a scoping review.

BACKGROUND: Appropriate and well-resourced medical internship training is important to ensure psychological health and well-being of doctors in training and also to recruit and retain these doctors. However, most reviews focused on clinical competency of medical interns instead of the non-clinical aspects of training. In this scoping review, we aim to review what tools exist to measure medical internship experience and summarize the major domains assessed. METHOD: The authors searched MEDLINE, Embase, PsycINFO, ERIC, and the Cochrane Library for peer-reviewed studies that provided quantitative data on medical intern's (house officer, foundation year doctor, etc.) internship experience and published between 2000 and 2019. Three reviewers screened studies for eligibility with inclusion criteria. Data including tools used, key themes examined, and psychometric properties within the study population were charted, collated, and summarized. Tools that were used in multiple studies, and tools with internal validity or reliability assessed directed in their intern population were reported. RESULTS: The authors identified 92 studies that were included in the analysis. The majority of studies were conducted in the US (n = 30, 32.6%) and the UK (n = 20, 21.7%), and only 14 studies (15.2%) were conducted in low- and middle-income countries. Major themes examined for internship experience included well-being, educational environment, and work condition and environment. For measuring well-being, standardized tools like the Maslach Burnout Inventory (for measuring burnout), Patient Health Questionnaire-9 (depression), General Health Questionnaire-12 or 30 (psychological distress) and Perceived Stress Scale (stress) were used multiple times. For educational environment and work condition and environment, there is a lack of widely used tools for interns that have undergone psychometric testing in this population other than the Postgraduate Hospital Educational Environment Measure, which has been used in four different countries. CONCLUSIONS: There are a large number of tools designed for measuring medical internship experience. International comparability of results from future studies would benefit if tools that have been more widely used are employed in studies on medical interns with further testing of their psychometric properties in different contexts.

Shocks, stress and everyday health system resilience: experiences from the Kenyan coast.

Health systems are faced with a wide variety of challenges. As complex adaptive systems, they respond differently and sometimes in unexpected ways to these challenges. We set out to examine the challenges experienced by the health system at a sub-national level in Kenya, a country that has recently undergone rapid devolution, using an 'everyday resilience' lens. We focussed on chronic stressors, rather than acute shocks in examining the responses and organizational capacities underpinning those responses, with a view to contributing to the understanding of health system resilience. We drew on learning and experiences gained through working with managers using a learning site approach over the years. We also collected in-depth qualitative data through informal observations, reflective meetings and in-depth interviews with middle-level managers (sub-county and hospital) and peripheral facility managers (n = 29). We analysed the data using a framework approach. Health managers reported a wide range of health system stressors related to resource scarcity, lack of clarity in roles and political interference, reduced autonomy and human resource management. The health managers adopted absorptive, adaptive and transformative strategies but with mixed effects on system functioning. Everyday resilience seemed to emerge from strategies enacted by managers drawing on a varying combination of organizational capacities depending on the stressor and context.

Incidence and risk factors for neonatal tetanus in admissions to Kilifi County Hospital, Kenya.

BACKGROUND: Neonatal Tetanus (NT) is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya. METHODS: We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999-2013) and identified cases of NT (standard clinical case definition) admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were tested for anti-tetanus antibodies. RESULTS: There were 191 NT admissions, of whom 187 (98%) were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89), P<0.001) but the case fatality (62%) did not change over the study period (P = 0.536). Younger infant age at admission (P = 0.001) was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82%) had undetectable levels of antitetanus antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate without protective levels. CONCLUSIONS: Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to expand coverage.

'The words will pass with the blowing wind': staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two African hospitals.

OBJECTIVE: To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future. METHODS: A social science sub-study of the FEAST (Fluid Expansion As Supportive Therapy) trial. Interviews were held with trial team members (n = 30), health workers (n = 15) and parents (n = 51) from two purposively selected hospitals in Soroti, Uganda, and Kilifi, Kenya. FINDINGS: Overall, deferred consent with prior assent was seen by staff and parents as having the potential to protect the interests of both patients and researchers, and to avoid delays in starting treatment. An important challenge is that the validity of verbal assent is undermined when inadequate initial information is poorly understood. This concern needs to be balanced against the possibility that full prior consent on admission potentially causes harm through introducing delays. Full prior consent also potentially imposes worries on parents that clinicians are uncertain about how to proceed and that clinicians want to absolve themselves of any responsibility for the child's outcome (some parents' interpretation of the need for signed consent). Voluntariness is clearly compromised for both verbal assent and full prior consent in a context of such vulnerability and stress. Further challenges in obtaining verbal assent were: what to do in the absence of the household decision-maker (often the father); and how medical staff handle parents not giving a clear agreement or refusal. CONCLUSION: While the challenges identified are faced in all research in low-income settings, they are magnified for emergency trials by the urgency of decision making and treatment needs. Consent options will need to be tailored to particular studies and settings, and might best be informed by consultation with staff members and community representatives using a deliberative approach.

Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis.

OBJECTIVES: Recent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Secondary level health facility: Kilifi, Coast, Kenya. PARTICIPANTS: Children aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. EXCLUSION CRITERIA: delayed development, epilepsy and sickle cell disease. RESULTS: During the study period, 665 children (median age 32 (IQR 20-46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period. CONCLUSION: The decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies.

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage.

BACKGROUND: Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence. METHODS: Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded. RESULTS: 954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01. CONCLUSION: There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.

Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia.

BACKGROUND: Children with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution. METHODS: A Phase II randomised controlled, safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock (non-diarrhoeal shock). Eligible children were randomised to HSD/5D or Ringer's Lactate (RL). A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours (as recommended by guidelines) while those randomised to RL received 10 ml/kg aliquots half hourly (maximum 40 ml/kg). Primary endpoint was resolution of shock at 8 and 24 hours. Secondary outcomes included resolution of acidosis, adverse events and mortality. RESULTS: 61 children were enrolled: 41 had shock and severe dehydrating diarrhoea, 20 had presumptive septic shock; 69% had decompensated shock. By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 (68%) and RL14/25 (52%), p = 0.39. Oliguria was more prevalent at 8 hours in the HSD/5D group, 9/22 (41%), compared to RL-3/25 (12%), p = 0.02. Mortality was high, HSD/5D-15/26(58%) and RL 13/29(45%); p = 0.42. Most deaths occurred within 48 hours of admission. Neither pulmonary oedema nor cardiogenic failure was detected. CONCLUSIONS: Outcome was universally poor characterised by persistence of shock, oliguria and high case fatality. Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy. Although isotonic fluid resuscitation did not result in cardiogenic heart failure, as previously feared, we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock. The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock, defining rate and volumes required to inform future guidelines. TRIAL REGISTRATION: The trial is registered as ISCRTN: 61146418.

Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria.

OBJECTIVES: A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution compared to other resuscitation fluids. Human albumin solution is expensive and not readily available in Africa. We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids, Dextran 70 and hydroxyethyl starch, to inform future trial design. DESIGN: An open-label randomized, controlled, phase II safety and efficacy trial. SETTING: High-dependency unit, Kilifi District Hospital, Kenya. PATIENTS: Children aged >6 months with severe falciparum malaria and acidosis (base deficit >8 mmol). INTERVENTIONS: Boluses (20-40 mL/kg) of 6% Dextran 70 and 6% hydroxyethyl starch (130/0.4). MEASUREMENTS AND MAIN RESULTS: Primary end point: resolution of shock over 8 hrs. Secondary end points include resolution of acidosis, in-hospital mortality, and adverse events (allergic reactions, pulmonary edema, and neurologic sequelae). A total of 79 children were enrolled: 39 received Dextran 70 and 40 received hydroxyethyl starch. No significant difference was observed in Dextran 70 and hydroxyethyl starch groups for shock resolution at 8 hrs: 23/37 (62%) and 25/39 (64%), respectively (p = .99). Acidosis resolution and respiratory distress were marginally superior in the hydroxyethyl starch group: 3/39 (8%) remained acidotic at 8 hrs versus 10/37 (27%) in the Dextran 70 arm (p = .05). There were four deaths (5%): two per arm, including three deaths in the coma subgroup (3/39, 8%). No other new adverse event was reported. CONCLUSIONS: Correction of shock by volume expansion with either Dextran 70 or hydroxyethyl starch in children with severe malaria acidosis is safe with low mortality, including the highest risk cases admitted in coma. Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria.