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

Diarrhoea Complicating Severe Acute Malnutrition in Kenyan Children: A Prospective Descriptive Study of Risk Factors and Outcome

BACKGROUND: Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. METHODS: A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (≥ 3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. RESULTS: At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Χ(2) = 17.6 p<0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Χ(2) = 16.6 p<0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference <10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p<0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Χ(2) = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. CONCLUSION: Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting

Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: Application to a population pharmacokinetics study in children with severe malnutrition

Article published in Journal of Chromatography BClinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200uL) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150mm×4.6mm i.d., 5um particle size) maintained at 40 ◦C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025 M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450 nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0 min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02–4ug/mL, with correlation coefficients (r2)≥0.998. Intraand inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6ug/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6ug/mL were 72.8±12.5% (n = 5), 83.5±5.2% and 77.7±2.0%, respectively (n = 8 in both cases). The recovery for IS was 94.5±7.9% (n = 15). The limits of detection and quantification were 10 ng/mL and 20 ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at −15 ◦C to −25 ◦C and −70 ◦C to −90 ◦C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children.Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200uL) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150mm×4.6mm i.d., 5um particle size) maintained at 40 ◦C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025 M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450 nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0 min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02–4ug/mL, with correlation coefficients (r2)≥0.998. Intraand inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6ug/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6ug/mL were 72.8±12.5% (n = 5), 83.5±5.2% and 77.7±2.0%, respectively (n = 8 in both cases). The recovery for IS was 94.5±7.9% (n = 15). The limits of detection and quantification were 10 ng/mL and 20 ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at −15 ◦C to −25 ◦C and −70 ◦C to −90 ◦C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children

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.</p

Blood culture isolates in children admitted with diarrhoea.

<p>Blood culture isolates in children admitted with diarrhoea.</p

Frequency of baseline clinical features in 1206 severely malnourished children.

<p> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038321#pone-0038321-t001" target="_blank"><b>Tables 1</b></a><b> and </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038321#pone-0038321-t002" target="_blank"><b>2</b></a><b> legend.</b></p>a<p>APLS definition.</p>b<p>Impaired consciousness  =  prostration or coma.</p>c<p>WHO definition of shock  =  impaired consciousness <i>plus</i> weak pulse volume <i>plus</i> CRT>3 seconds.</p>d<p>WHO features of severe dehydration  = 2 or more of (sunken eyes or decreased skin turgour or lethargy or inability to drink).</p>e<p>WHO Danger signs  =  Hypothermia or hypoglycaemia or lethargy.</p

Kaplan-Meier plot of survival time of children with SAM admitted with and without diarrhoea.

<p>Kaplan-Meier plot of survival time of children with SAM admitted with and without diarrhoea.</p

Clinical and laboratory features by mortality of 592 children admitted with diarrhoea.

<p>Clinical and laboratory features by mortality of 592 children admitted with diarrhoea.</p

Multivariable logistic regression variables associated with death in children with severe malnutrition and diarrhoea at admission.

<p>Different models with and without low MUAC were tested because MUAC has been reported to vary with hydration status.</p

Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: Application to a population pharmacokinetics study in children with severe malnutrition

Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200 μL) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150 mm × 4.6 mm i.d., 5 μm particle size) maintained at 40 °C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025 M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450 nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0 min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02–4 μg/mL, with correlation coefficients (r2) ≥ 0.998. Intra- and inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6 μg/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6 μg/mL were 72.8 ± 12.5% (n = 5), 83.5 ± 5.2% and 77.7 ± 2.0%, respectively (n = 8 in both cases). The recovery for IS was 94.5 ± 7.9% (n = 15). The limits of detection and quantification were 10 ng/mL and 20 ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at −15 °C to −25 °C and −70 °C to −90 °C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children