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C Waruiru

Publications and source records attributed to C Waruiru.

At least 19 recordsLinked to original sources
PubMed2004

Febrile seizures: an update.

This review focuses on the latest knowledge and understanding of febrile seizures and outlines the more important issues in the management of children who present with an apparent "febrile seizure". It is not the remit of this paper to discuss the detailed management of febrile seizures. Throughout this review, the words "partial" and "focal" will be used interchangeably and the term "febrile seizure" (FS) will be used, reflecting the proposed changes in the terminology of seizures and epilepsies.1

Anticonvulsants↗
PubMed2000

Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study.

BACKGROUND: Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria. METHODS: Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat. FINDINGS: 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]). INTERPRETATION: In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.

Adolescent↗
PubMed2000

Paediatric survival and re-admission risks following hospitalization on the Kenyan coast.

The district general hospital (DGH) is a common feature of health service provision in many developing countries. We have used linked demographic and clinical surveillance in a rural community located close to a DGH on the Kenyan coast to define the use and public health significance of essential clinical services provided by it. Of a birth cohort of over 4000 children followed for approximately 6 years, about a third were admitted to hospital at least once. Significantly more children admitted with major infectious diseases such as malaria and acute respiratory tract infections were readmitted with the same condition during the surveillance period than would have been expected by chance. Among surviving admissions, mortality post-discharge was significantly higher than in the cohort which had not been admitted within 3, 6 and 12 months. Most of the patients who died after discharge had been admitted with a diagnosis of gastroenteritis. Most children admitted to the DGH survive hospitalization and the remaining period of childhood. Despite no clinical trial evidence to support the claim, it seems reasonable to assume that in the absence of intensive clinical management provided by a DGH, a significant proportion of these children would not have survived. However, the DGH is able to define a group of at-risk children who re-present with severe complications of infectious disease, and of these several may have underlying conditions not amenable to DGH intervention and continue to have a poor prognosis. Both groups of children represent statistically significant subsets of a rural paediatric community and the future organization and co-ordination of DGH and primary care services need to work in unison to strengthen the service needs of children at risk.

Child↗
PubMed2000

Arginine vasopressin secretion in Kenyan children with severe malaria.

Hyponatraemia is common in African children with severe malaria, but the cause is unknown. We measured plasma sodium (p[Na]) and arginine vasopressin concentrations (p[AVP]) in 30 consecutive children with severe malaria (19 had cerebral malaria), on admission, at 48 and 96 h after admission. Hyponatraemia (p[Na] < 130 mmol/l) occurred in 53 per cent of the children and was unrelated to peripheral parasite density, dehydration or abnormal renal function. The highest p[AVP] were seen in patients with cerebral malaria. Overall, p[AVP] declined 96 h after treatment. In children with hyponatraemia (cerebral and non-cerebral), p[AVP] levels were not suppressed and in 67 per cent of cases they were deemed inappropriate. Inappropriate AVP secretion is common in children with severe malaria and may influence fluid therapy after correction of initial dehydration.

Arginine Vasopressin↗
PubMed2000

Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism?

The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an age-matched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations were decreased (geometric mean ratio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.

Antimalarials↗
PubMed1997

Acidosis in severe childhood malaria.

Data were prospectively collected on 306 Kenyan children, including blood gases in 258 (75%). Severe malaria caused a predominantly high-anion-gap metabolic acidosis in at least 43% of children. Children with coma and respiratory distress (CM + RD) had greater evidence of renal dysfunction, lower mean pH and higher mean plasma osmolality than those with respiratory distress (RD) or coma (CM) as isolated findings (mean urea 10.7 vs. 6.0 vs. 4.3 mmol/l; mean creatinine 97 vs. 74 vs. 58 mumol/l; mean osmolality 301 vs. 288 vs. 283 mosmol/l; and mean pH 7.16 vs. 7.29 vs. 7.39, respectively, p < 0.001 for each comparison of CM + RD vs. RD or CM). In addition, children with CM + RD had a higher mean blood lactate (6.7 vs. 3.3 mmol/l, p < 0.001), a lower mean haemoglobin (5.5 vs. 7.0 g/dl, p = 0.002) and a lower mean age (26.4 vs. 41.9 months, p < 0.001) than children with CM and accounted for 15/24 (63%) of all deaths. These and previous data implicate hypovolaemia and renal impairment in the pathogenesis of metabolic acidosis in severe childhood malaria. In children who are acidotic, anaemia is strongly associated with lactic acidaemia and may therefore contribute to its pathogenesis. These data also imply that coma in acidotic children (CM + RD) and those with an isolated encephalopathy (CM) may result from quite different pathophysiological mechanisms.

Acidosis↗
PubMed1997

The influence of alanine infusion on glucose production in 'malnourished' African children with falciparum malaria.

By US standards, about half of African children are malnourished, although most appear clinically normal. It is possible that precursor supply for gluconeogenesis is limited to a greater extent in these seemingly malnourished African children than in healthy children, consequently limiting glucose production. Since in malaria peripheral glucose utilization is increased, precursor supply could play an even more critical role in maintaining glucose production in African children suffering from falciparum malaria. We studied the effect of alanine infusion (1.5 mg/kg/min) on glucose production (measured by infusion of [6,6-2H2]glucose) and plasma glucose concentration in 10 consecutive children with acute, uncomplicated falciparum malaria. By US standards, six children were below the 10th percentile of weight for height and seven were below the 10th percentile of height for age. Plasma concentrations of alanine increased during alanine infusion from 153 +/- 21 to 468 +/- 39 mumol/l, whereas plasma lactate concentrations did not change (1.4 +/- 0.2 vs. 1.3 +/- 0.2 mmol/l). Plasma glucose concentration and glucose production did not change during alanine infusion: 4.6 +/- 0.3 vs. 4.5 +/- 0.3 mmol/l and 5.8 +/- 0.4 vs. 5.7 +/- 0.3 mg/kg/min, respectively. Gluconeogenic precursor supply is sufficient for maintainance of glucose production in African children with uncomplicated malaria who are malnourished by US standards.

Acute Disease↗
PubMed1997

Intracranial hypertension in Africans with cerebral malaria.

The causes of death and neurological sequelae in African children with cerebral malaria are obscure. Intracranial pressure (ICP) was monitored and cerebral perfusion pressure (CPP) calculated in 23 Kenyan children with cerebral malaria. Four children had severe intracranial hypertension (ICP > 40 mm Hg, CPP < 40 mm Hg): two died, one with an ICP of 158 mm Hg and signs of transtentorial herniation, the other one with an ICP of 42 mm Hg and cardiorespiratory arrest. The other two survived with severe neurological sequelae. Nine had intermediate intracranial hypertension (ICP > 20 mm Hg, CPP < 50 mm Hg) and 10 had mild intracranial hypertension (maximum ICP 10-20 mm Hg); all survived without severe sequelae. Mannitol controlled the ICP in children with intermediate intracranial hypertension, but it did not prevent the development of intractable intracranial hypertension in children with severe intracranial hypertension. Intracranial hypertension is a feature of Kenyan children with cerebral malaria and severe intracranial hypertension is associated with a poor outcome.

Child↗
PubMed1996

Seizures and status epilepticus in childhood cerebral malaria.

Prolonged, multiple seizures complicate a high proportion of cases of childhood cerebral malaria, and several studies have shown an association between these and neurological sequelae. We prospectively studied 65 patients (38 female) admitted to Kilifi Hospital in 1994. Electroencephalographic recordings (EEGs) were made at 12-hourly intervals, with continuous recordings made on a cerebral function analysing monitor (CFAM). Survivors were seen one month after discharge. Cerebral computerized tomography was performed on children with neurological sequelae. Sixty-two percent of patients had seizures following admission, of whom half had an episode of status epilepticus. Fifty-two percent of seizures were partial motor, 34% generalized tonic-clonic, and 14% partial with secondary generalization. In 22%, coma appeared to be due to a prolonged postictal state. Ten children had subtle motor seizures. Posterior parieto-temporal discharges were the most common EEG finding. Seven children died, eight developed neurological sequelae, and 50 (77%) recovered fully. Status epilepticus was associated with the development of neurological sequelae. Prolonged, multiple seizures may play an important part in the pathogenesis of coma in childhood cerebral malaria, and are likely to contribute to both the morbidity and mortality of this disease.

Brain↗
PubMed1996

Hyponatraemia and dehydration in severe malaria.

The prevalence and likely cause of hyponatraemia in severe childhood malaria were investigated. One hundred and thirty two children, 47 of whom had cerebral malaria, were prospectively recruited and serial simple indices of fluid and electrolyte balance and renal function monitored during admission. In 55%, hyponatraemia (sodium < 135 mmol/l) was present on admission. Hyponatraemia was pronounced (sodium < or = 130 mmol/l) in 21%, and these children gained less weight during admission (mean weight gain 2.4% v 4.3%) than children with a normal sodium (135-145 mmol/l). Overall, 31% of survivors were at least moderately dehydrated on admission (5% weight gain by discharge). These children had higher plasma urea concentrations on admission (6.1 v 4.5 mmol/l) and were more acidotic (mean base excess -12.1 v -8.0) than children who were not dehydrated. There were changes in simple indices of renal function between admission and discharge in children who survived (creatinine 65.7 v 37.9 mumol/l and urea 5.5 v 1.9 mmol/l). The results suggest that dehydration is common in severe childhood malaria, that it may contribute to mild impairment in renal function, and that hyponatraemic children are less water depleted, showing appropriate rather than inappropriate secretion of antidiuretic hormone.

Child, Preschool↗
PubMed1996

Deep breathing in children with severe malaria: indicator of metabolic acidosis and poor outcome.

Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.

Acidosis↗
PubMed1996

Transfusion for respiratory distress in life-threatening childhood malaria.

We have prospectively collected information during resuscitation in 24 children with life-threatening malaria. All had clinical respiratory distress and 16 were severely anemic (hemoglobin < or = 5 g/dL) on admission. Central venous pressure (CVP) measurements were normal (< or = 5 cm of water) prior to treatment but all had a metabolic acidosis. The geometric mean lactate level was significantly higher in children admitted with severe anemia than in those without severe anemia (11.2 mmol/l versus 4.2 mmol/l; P = 0.009). Hypovolemia (a CVP on admission < 0 cm of water) was associated, although not significantly, with a higher admission plasma creatinine concentration (94 mumol/l versus 64 mumol/l; P = 0.06) and probably contributed to the severely reduced creatinine clearances (0-39 ml/min/1.73 ml2) found in 12 of the 13 children in whom this was assessed in the first 24 hr. Treatment resulted in a rapid decrease in blood lactate in 16 of the 13 children in whom this was assessed in the first 24 hr. Treatment resulted in a rapid decrease in blood lactate in 16 of the 20 children transfused, which was most dramatic in severely anemic children, who were rapidly resuscitated. In nonanemic children, early and rapid administration of normal saline usually resulted in both metabolic and clinical improvement. However, in three children, two of whom died, acidosis persisted despite resuscitation. Metabolic acidosis often accounts for respiratory distress in life-threatening childhood malaria. Severe anemia and hypovolemia appear to play major roles in its pathogenesis, are readily treatable, and there appears to be little risk of congestive cardiac failure even with an aggressive approach to fluid replacement.

Acidosis↗
PubMed1995

Indicators of life-threatening malaria in African children.

BACKGROUND: About 90 percent of the deaths from malaria are in African children, but criteria to guide the recognition and management of severe malaria have not been validated in them. METHODS: We conducted a prospective study of all children admitted to the pediatric ward of a Kenyan district hospital with a primary diagnosis of malaria. We calculated the frequency and mortality rate for each of the clinical and laboratory criteria in the current World Health Organization (WHO) definition of severe malaria, and then used logistic-regression analysis to identify the variables with the greatest prognostic value. RESULTS: We studied 1844 children (mean age, 26.4 months) with a primary diagnosis of malaria. Not included were 18 children who died on arrival and 4 who died of other causes. The mortality rate was 3.5 percent (95 percent confidence interval, 2.7 to 4.3 percent), and 84 percent of the deaths occurred within 24 hours of admission. Logistic-regression analysis identified four key prognostic indicators: impaired consciousness (relative risk, 3.3; 95 percent confidence interval, 1.6 to 7.0), respiratory distress (relative risk, 3.9; 95 percent confidence interval, 2.0 to 7.7), hypoglycemia (relative risk, 3.3; 95 percent confidence interval, 1.6 to 6.7), and jaundice (relative risk, 2.6; 95 percent confidence interval, 1.1 to 6.3). Of the 64 children who died, 54 were among those with impaired consciousness (n = 336; case fatality rate, 11.9 percent) or respiratory distress (n = 251; case fatality rate, 13.9 percent), or both. Hence, this simple bedside index identified 84.4 percent of the fatal cases, as compared with the 79.7 percent identified by the current WHO criteria. CONCLUSIONS: In African children with malaria, the presence of impaired consciousness or respiratory distress can identify those at high risk for death.

Anemia↗
PubMed1995

The management of severe malaria in children: a review.

We have attempted to summarise an approach to management of severe malaria from our experience and that of others from published data in this review. This represents our current state of knowledge and practices which may change as research continues in this field. It also represents what we feel should be the minimum aim in treating severe malaria even at district hospital level. It focuses on practical issues encountered when admitting such patients: initial assessment, immediate supportive management, use of transfusion, appropriate anti-malarial treatment and ongoing management.

Child↗
PubMed1994

Brain swelling and ischaemia in Kenyans with cerebral malaria.

Computed tomography was performed on 14 unconscious Kenyan children recovering from cerebral malaria (seven of whom had another scan 12-120 days later) to elucidate the cause of intracranial hypertension and neurological sequelae. Brain swelling, defined as a loss of cerebrospinal fluid spaces, was documented in six children, while a further two had conspicuously small ventricles only. There was severe intracranial hypertension in the two children with definite brain swelling in whom intracranial pressure was monitored. There was no evidence of acute hydrocephalus or vasogenic oedema. Four children with brain swelling also had widespread low density areas suggestive of ischaemic damage. The patterns of damage were not uniform but were consistent with a critical reduction in cerebral perfusion pressure (which was documented in the two in whom this was monitored), hypoglycaemia, or status epilepticus. All four had serious neurological sequelae. These data suggest that brain injury in cerebral malaria may be due in part to secondary systemic and intracranial factors as well as to the direct effect of intravascular sequestration.

Brain↗
PubMed1992

Childhood deaths in Africa: uses and limitations of verbal autopsies.

The verbal autopsy (VA) is an epidemiological tool that is widely used to ascribe causes of death by interviewing bereaved relatives of children who were not under medical supervision at the time of death. This technique was assessed by comparison with a prospective survey of 303 childhood deaths at a district hospital in Kenya where medically confirmed diagnoses were available. Common causes of death were detected by VA with specificities greater than 80%. Sensitivity of the VA technique was greater than 75% for measles, neonatal tetanus, malnutrition, and trauma-related deaths; however, malaria, anaemia, acute respiratory-tract infection, gastroenteritis, and meningitis were detected with sensitivities of less than 50%. There may have been unwarranted optimism in the ability of VAs to detect some of the major causes of death, such as malaria, in African children. VA used in malaria-specific intervention trials should be interpreted with caution and only in the light of known sensitivities and specificities.

Cause of Death↗
PubMedDate not supplied

Periodicity and space-time clustering of severe childhood malaria on the coast of Kenya.

Traditionally malaria epidemiology has focused on factors such as parasite rates and vector dynamics without specific reference to disease. There are limited comprehensive data on malaria as a life-threatening event in African children. We have identified, through hospital surveillance, 581 episodes of severe malaria in residents of a defined area on the Kenya coast over a period of 3 years. This represents an absolute minimum risk of developing severe malaria by the fifth birthday of 1 in 15. The presentation of severe malaria showed marked seasonality, but the timing and magnitude of these fluctuations varied considerably between years. A satellite navigational system was used to define the exact location of the home of each severe malaria case. Space-time clustering of severe malaria was evident in this community. Seasonal peaks in incidence of severe malaria may comprise discrete mini-epidemics. In contrast, parasite rates in the community varied little during the course of the surveillance. The monitoring of disease, as opposed to parasitization, in children may result in more effective targeting of intervention resources.

Age Factors↗