Developmental inventories using illiterate parents as informants: Communicative Development Inventory (CDI) adaptation for two Kenyan languages.

Communicative Development Inventories (CDIs, parent-completed language development checklists) are a helpful tool to assess language in children who are unused to interaction with unfamiliar adults. Generally, CDIs are completed in written form, but in developing country settings parents may have insufficient literacy to complete them alone. We designed CDIs to assess language development in children aged 0;8 to 2;4 in two languages used in Coastal communities in Kenya. Measures of vocabulary, gestures, and grammatical constructions were developed using both interviews with parents from varying backgrounds, and vocabulary as well as grammatical constructions from recordings of children's spontaneous speech. The CDIs were then administered in interview format to over 300 families. Reliability and validity ranged from acceptable to excellent, supporting the use of CDIs when direct language testing is impractical, even when children have multiple caregivers and where respondents have low literacy levels.

Perceptions, social life, treatment and education gap of Tanzanian children with epilepsy: a community-based study.

The effects of epilepsy on children and their families, factors influencing the treatment and education gap and socio-cultural beliefs about epilepsy in children in rural sub-Saharan Africa are not clearly defined. We conducted a qualitative study, with 38 in-depth interviews and 2 focus group discussions with carers of children with epilepsy (CWE) in Tanzania. Discrimination, isolation and lack of hope were identified as major issues. Poor school attendance was attributed to learning difficulties, behavior problems, ongoing seizures and restricted school access. The treatment gap was related to misdiagnosis, preferential use of traditional treatment and cost of biomedical treatment. The hopes expressed for the future centered on access to treatment and education. Improved access to diagnosis, cost-effective treatment, sensitization of the community on epilepsy, collaborative care provision with traditional and faith healers and improved access to specialist schooling could improve the quality of life and future of CWE in this region.

Characteristics and outcome of cardiopulmonary resuscitation in hospitalised African children.

OBJECTIVE: To review the characteristics and outcome of cardiopulmonary resuscitation in children at a rural hospital in Kenya. PATIENTS AND METHOD: All children aged 0-14 years who experienced > or =1 episode of respiratory or cardiopulmonary arrest during April 2002--2004 were prospectively identified. Demographic variables, cause of hospitalisation, type and duration of arrest, resuscitation measures taken and outcomes were determined. RESULTS: 114 children experienced at least one episode of respiratory arrest (RA) or cardiopulmonary arrest (CPA). Cardiopulmonary resuscitation (CPR) was performed on all children. "Do not resuscitate order" (DNR) was given in 15 patients after initial resuscitation. Eighty two patients (72%) had RA and 32 (28%) had CPA. 25/82 (30%) patients with RA survived initial CPR compared to 5/32 (16%) with CPA. Survival at discharge was 22% (18/82) in children who had RA while no one with CPA survived at discharge. The leading underlying diseases were severe malaria, septicaemia and severe malnutrition. Prolonged resuscitation beyond 15 min and receiving adrenaline [epinephrine] (at least one dose of 10 microg/kg IV) were predictive of poor final outcome. CONCLUSION: Cardiopulmonary arrest after admission has a very poor prognosis in our hospital. Infectious diseases are the main underlying causes of arrest. If a child fails to respond to the basic tenements of PALS within 15 min then it is unlikely that further efforts to sustain life will be fruitful in hospitals where ventilation facilities are not present.

Response to diazepam in children with malaria-induced seizures.

Malaria infection reduces the binding capacity of benzodiazepine receptors in mice. We studied the efficacy of diazepam terminating seizures in children with falciparum malaria. Diazepam stopped seizures in fewer patients with malaria parasitaemia (chi(2)=3.93, P=0.047) and those with clinical diagnosis of malaria (chi(2)=9.84, P=0.002) compared to those without. However malaria was not identified as an independent risk factor for diazepam's failure to stop seizures in children.

Monitoring psychomotor development in a resource-limited setting: an evaluation of the Kilifi Developmental Inventory.

BACKGROUND: Modifications made to the Kilifi Developmental Checklist and the psychometric characteristics of the new measure (The Kilifi Developmental Inventory) which assess the psychomotor functioning of children aged 6-35 months are described. METHODS: Two groups of community children (319 rural and 104 urban dwellers) and nine children with neurodevelopmental disorders were recruited for a cross-sectional study. RESULTS: In both a rural and urban reference population, the inventory showed excellent internal consistency, interobserver agreement, test-retest reliability and sensitivity to maturational changes. Children with neurodevelopmental impairment and those who were underweight had significantly lower scores than the community sample, attesting to the sensitivity of the measure. Mothers found the assessment procedures acceptable and informative. CONCLUSIONS: The Kilifi Developmental Inventory is a culturally appropriate measure that can be used to monitor and describe the development of at-risk children in resource-limited settings in Kenya.

Haemolytic uraemic syndrome in children admitted to a rural district hospital in Kenya.

We studied children admitted to Kilifi District Hospital, Kenya, between 1997 and 2005 with haemolytic uraemic syndrome (HUS) and reviewed their records in order to determine the clinical features and outcomes of the disease. Thirty-one children fulfilled the criteria: 21 (68%) had diarrhoea-associated HUS (D + HUS), the remainder did not (D-HUS); five had involvement of the central nervous system. Those with D-HUS had lower haemoglobin and platelet counts when compared with those with D + HUS. The overall mortality rate was 55% (17/31) with no significant difference between the two groups. Severe hyponatraemia ([Na(+)] <120 mmol/L) predicted a poor outcome. Shigella dysenteriae was the most common isolated organism in the stool and Escherichia coli and S. dysenteriae were the most common blood isolates. HUS carries a high mortality rate and D-HUS is as common as D + HUS.

Prevalence, incidence and risk factors of epilepsy in older children in rural Kenya.

BACKGROUND: There is little data on the burden or causes of epilepsy in developing countries, particularly in children living in sub-Saharan Africa. METHODS: We conducted two surveys to estimate the prevalence, incidence and risk factors of epilepsy in children in a rural district of Kenya. All children born between 1991 and 1995 were screened with a questionnaire in 2001 and 2003, and those with a positive response were then assessed for epilepsy by a clinician. Active epilepsy was defined as two or more unprovoked seizures with one in the last year. RESULTS: In the first survey 10,218 children were identified from a census, of whom 110 had epilepsy. The adjusted prevalence estimates of lifetime and active epilepsy were 41/1000 (95% CI: 31-51) and 11/1000 (95% CI: 5-15), respectively. Overall two-thirds of children had either generalized tonic-clonic and/or secondary generalized seizures. A positive history of febrile seizures (OR=3.01; 95% CI: 1.50-6.01) and family history of epilepsy (OR=2.55; 95% CI: 1.19-5.46) were important risk factors for active epilepsy. After the second survey, 39 children from the same birth cohort with previously undiagnosed epilepsy were identified, thus the incidence rate of active epilepsy is 187 per 100,000 per year (95% CI: 133-256) in children aged 6-12 years. CONCLUSIONS: There is a considerable burden of epilepsy in older children living in this area of rural Kenya, with a family history of seizures and a history of febrile seizures identified as risk factors for developing epilepsy.

Cerebrospinal Fluid Studies in Kenyan Children with Severe Falciparum Malaria.

The pathogenesis of the neurological complications of Plasmodium falciparum malaria is unclear. We measured proteins and amino acids in paired plasma and cerebrospinal fluid (CSF) samples in children with severe falciparum malaria, to assess the integrity of the blood brain barrier (BBB), and look for evidence of intrathecal synthesis of immunoglobulins, excitotoxins and brain damage. METHODS: Proteins of different molecular sizes and immunoglobulins were measured in paired CSF and plasma samples in children with falciparum malaria and either impaired consciousness, prostrate, or seizures. RESULTS: The ratio of CSF to plasma albumin (Q(alb)) exceeded the reference values in 42 (51%) children. The CSF concentrations of the excitotoxic amino acid aspartate and many non-polar amino acids, except alanine, were above the reference value, despite normal plasma concentrations. IgM concentrations were elevated in 21 (46%) and the IgM index was raised in 22 (52%). Identical IgG oligoclonal bands were found in 9 (35%), but only one patient had an increase in the CSF IgG without a concomitant increase in plasma indicating intrathecal synthesis of IgG. CONCLUSIONS: This study indicates that the BBB is mildly impaired in some children with severe falciparum malaria, and this impairment is not confined to cerebral malaria, but also occurs in children with prostrate malaria and to a lesser extent the children with malaria and seizures. There is evidence of intrathecal synthesis of immunoglobulins in children with malaria, but this requires further investigation. This finding, together with raised level of excitotoxic amino acid aspartate could contribute to the pathogenesis of neurological complications in malaria.

Computerized tomography scan of the brain in a community study of neurological impairment in Kenya.

Neurological impairment is common in resource-poor countries, but its causes are not clear. Computerized tomography (CT) of the brain has been used to determine the cause of brain insults that may manifest as neurological impairments. The authors conducted a community survey in Kilifi of 10 218 children aged 6 to 9 years to detect neurological impairment. From this survey, 34 children were identified, of whom 16 had motor deficits, 11 complex partial seizures, 4 microcephaly or macrocephaly, and 3 severe developmental delay. These children were assessed with elicitation of history, physical examination, and CT scan of the brain. Sixteen (47%) of the scans showed abnormalities: cerebral atrophy (n = 9), schizencephaly (n = 3), periventricular leukomalacia (n = 2), porencephalic cyst (n = 1), and agenesis of the corpus callosum (n = 1). The minimum prevalence of abnormalities on the CT scan of the brain is 1.56 of 1000, and the prevalence of schizencephaly is 0.29 of 1000. Motor impairments were more likely to show abnormality than the other indications. CT abnormalities are common in children with neurological impairment in Kenya, but the appearances did not identify a major cause.

Identifying children with neurological impairment and disability in resource-poor countries.

BACKGROUND: The burden of neurological impairment (NI) in children living in resource-poor countries (RPCs) is unknown. This lack of data is caused by inappropriate case detection techniques. In RPCs, the most appropriate method should be inexpensive, simple, rapid and accurate. This article reviews methods used to identify children with NI and disability in RPCs, evaluating their effectiveness and suitability. METHODS: A search of relevant articles was performed using the National Library of Medicine via PubMed and Medline search engines. In addition, bibliographies of reviews were also browsed to identify additional articles, particularly those from World Health Organization and United Nations sources and from government and unpublished reports. Key phrases used included impairment, disability or handicap and the following terms: identification, screening, prevalence and developing countries. Studies included were those that fulfilled the following criteria; performed in RPCs, presented data in detail to allow reanalysis and provided data on cost and validity of the methods. RESULTS: Use of the national census, key informants and methods using rapid rural appraisal have low sensitivity and are not able to provide adequate information on diagnostic categories or risk factors. House-to-house surveys using questionnaires have high sensitivities (63-100%) in the detection of impairment, but this approach remains relatively expensive and cannot be applied to an entire population (e.g. a region or country) and is thus less useful for assessing the needs of disability. Furthermore, the sensitivity is decreased in the detection of some domains, e.g. cognition. CONCLUSIONS: Most of the approaches used for identifying individuals with NI or disability suffer from inadequacies, the main ones being low sensitivity and underreporting. To assess the burden, nationwide censuses combined with surveys in selected areas of the country may be useful. These systems, however, require validation to establish their suitability.

Medical informatics in medical research - the Severe Malaria in African Children (SMAC) Network's experience.

OBJECTIVES: Computers are widely used for data management in clinical trials in the developed countries, unlike in developing countries. Dependable systems are vital for data management, and medical decision making in clinical research. Monitoring and evaluation of data management is critical. In this paper we describe database structures and procedures of systems used to implement, coordinate, and sustain data management in Africa. We outline major lessons, challenges and successes achieved, and recommendations to improve medical informatics application in biomedical research in sub-Saharan Africa. METHODS: A consortium of experienced research units at five sites in Africa in studying children with disease formed a new clinical trials network, Severe Malaria in African Children. In December 2000, the network introduced an observational study involving these hospital-based sites. After prototyping, relational database management systems were implemented for data entry and verification, data submission and quality assurance monitoring. RESULTS: Between 2000 and 2005, 25,858 patients were enrolled. Failure to meet data submission deadline and data entry errors correlated positively (correlation coefficient, r = 0.82), with more errors occurring when data was submitted late. Data submission lateness correlated inversely with hospital admissions (r = -0.62). CONCLUSIONS: Developing and sustaining dependable DBMS, ongoing modifications to optimize data management is crucial for clinical studies. Monitoring and communication systems are vital in multi-center networks for good data management. Data timeliness is associated with data quality and hospital admissions.

The reliability of diagnostic techniques in the diagnosis and management of malaria in the absence of a gold standard.

The accuracy of techniques for the diagnosis of malaria are usually compared with optical microscopy, which is considered to be a gold standard. However, microscopy is prone to error and therefore makes it difficult to assess the reliability of other diagnostic techniques. We did a systematic review to assess the specificity and sensitivity of diagnostic techniques in different settings, using a statistical method that avoided defining a gold standard. Performance varied depending on species of the malaria parasite, level of parasitaemia, and immunity. Overall, histidine-rich protein 2 (HRP2)-based dipsticks showed a high sensitivity (92.7%) and specificity (99.2%) for Plasmodium falciparum in endemic areas. The acridine orange test was more sensitive (97.1%) in detecting P falciparum in epidemiological studies, with a specificity of 97.9%. In the absence of a gold standard, HRP2 dipsticks and acridine orange could provide an alternative for detecting falciparum infections in endemic areas and epidemiological studies, respectively. Microscopy still remains more reliable in detecting non-falciparum infections.

Research priorities in the management of severe Plasmodium falciparum malaria in children.

Severe malaria is a common reason for admission to paediatric wards in hospitals across sub-Saharan Africa. Despite over 100 years of research, mortality remains high. Deaths are associated with severe metabolic acidosis, shock, severe anaemia, hypoglycaemia, impaired consciousness, raised intracranial pressure, and status epilepticus. Most inpatient deaths occur within 24 h of admission to hospital, before the beneficial effects of treatment with antimalarial drugs are achieved. This review covers the priority areas for research in the care of children with severe malaria, addressing each of the main risk factors associated with death, in a bid to reduce the inpatient mortality.

Prevalence and risk factors of neurological disability and impairment in children living in rural Kenya.

BACKGROUND: There is little data on the burden of neurological impairment (NI) in developing countries, particularly in children of Africa. METHODS: We conducted a survey of NI in children aged 6-9 years in a rural district of Kenya. First, we screened for neurological disability by administering the Ten Questions Questionnaire (TQQ) to parents/guardians of children in a defined population. In phase two, we performed a comprehensive clinical and psychological assessment on children who tested positive on TQQ and on a similar number of children who tested negative. RESULTS: A total of 10 218 children were screened, of whom 955 (9.3%) were positive on TQQ. Of these, 810 (84.8%) were assessed, and of those who tested negative 766 (8.3%) were assessed. The prevalence for moderate/severe NI was 61/1000 [95% confidence interval (95% CI) 48-74]. The most common domains affected were epilepsy (41/1000), cognition (31/1000), and hearing (14/1000). Motor (5/1000) and vision (2/1000) impairments were less common. Of the neurologically impaired children (n = 251), 56 (22%) had more than one impairment. Neonatal insults were found to have a significant association with moderate/severe NI in both the univariate [odds ratio (OR) = 1.70; 95% CI 1.12-2.47] and multivariate analyses (OR = 1.30; 95% CI 1.09-1.65). CONCLUSIONS: There is a considerable burden of moderate/severe NI in this area of rural Kenya, with epilepsy, cognition, and hearing being the most common domains affected. Neonatal insults were identified as an important risk factor.

Risk factors for persisting neurological and cognitive impairments following cerebral malaria.

BACKGROUND: Persisting neurological and cognitive impairments are common after cerebral malaria. Although risk factors for gross deficits on discharge have been described, few studies have examined those associated with persistent impairments. METHODS: The risk factors for impairments following cerebral malaria were determined by examining hospital records of 143 children aged 6-9 years, previously admitted with cerebral malaria, who were assessed at least 20 months after discharge to detect motor, speech and language, and other cognitive (memory, attention, and non-verbal functioning) impairments. RESULTS: The median age on admission was 30 months (IQR 19-42) and the median time from discharge to assessment was 64 months (IQR 40-78). Thirty four children (23.8%) were defined as having impairments: 14 (9.8%) in motor, 16 (11.2%) in speech and language, and 20 (14.0%) in other cognitive functions. Previous seizures (OR 5.6, 95% CI 2.0 to 16.0), deep coma on admission (OR 28.8, 95% CI 3.0 to 280), focal neurological signs observed during admission (OR 4.6, 95% CI 1.1 to 19.6), and neurological deficits on discharge (OR 4.5, 95% CI 1.4 to 13.8) were independently associated with persisting impairments. In addition, multiple seizures were associated with motor impairment, age <3 years, severe malnutrition, features of intracranial hypertension, and hypoglycaemia with language impairments, while prolonged coma, severe malnutrition, and hypoglycaemia were associated with impairments in other cognitive functions. CONCLUSIONS: Risk factors for persisting neurological and cognitive impairments following cerebral malaria include multiple seizures, deep/prolonged coma, hypoglycaemia, and clinical features of intracranial hypertension. Although there are overlaps in impaired functions and risk factors, the differences in risk factors for specific functions may suggest separate mechanisms for neuronal damage. These factors could form the basis of future preventive strategies for persisting impairments.

Withdrawal of parenteral phenobarbitone--implications for resource-poor countries.

Parenteral phenobarbitone is an integral part of the management of status epilepticus, especially in the context of resource-poor countries. It is highly effective at controlling seizures. It is safe, cheap, can be given by rapid intravenous push or intramuscular route, boluses can be repeated, and it is recommended as part of the Advanced Paediatric Life Support guidelines. The proposed alternatives lack efficacy, practicality and/or place the child in status epilepticus at risk of respiratory compromise. The impact of the loss of parenteral phenobarbitone would be increased cardiac complications, lack of early seizure control, prolonged seizures resulting in brain damage and systemic complications. Increased numbers of patients will require artificial ventilation in centres without facilities, and centres with facilities will be unable to cope with the load of ventilated patients because of lack of safe transport systems and bed space.

Comparison of axillary, rectal and tympanic temperature measurements in children admitted with malaria.

We compared axillary, rectal and tympanic temperatures in children admitted with severe malaria. The axillary temperatures were 0.74 degrees C (95% limits of agreement -0.85 to 2.33 degrees C) less than rectal temperatures and tympanic temperatures 0.42 degrees C (95% limits of agreement -0.16 to 2.44 degrees C) less than rectal temperatures. The difference was greater on admission than 24 hours later. These differences may be important in defining criteria for clinical syndromes.

The role of sequential administration of sulphadoxine/pyrimethamine following quinine in the treatment of severe falciparum malaria in children.

Sulphadoxine/pyrimethamine (SP) is often administered with quinine in the treatment of severe falciparum malaria to shorten the course of quinine. The efficacy of SP alone in the treatment of non-severe malaria has been declining rapidly in East Africa, raising concerns of the usefulness of a shortened course of quinine followed SP. We audited the efficacy of quinine/SP in the treatment of severe malaria in Kenyan children. Children with severe falciparum malaria were treated with parenteral quinine followed by a single oral dose of SP. A clinical evaluation was performed 3 weeks later in which a blood sample was obtained for full haemogram, blood slide and analysis of the parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) codons, mutations of which are associated with resistance to SP. A total of 452 children were enrolled, of whom 374 completed the study. Fifty-two (13.9%) children were parasitaemic by 3 weeks of whom 17 (4.5%) had fever as well. The treatment failure group had a significantly higher parasitaemia (129 061 vs. 43 339; P<0.001) and haemoglobin on admission, but only admission parasitaemia independently predicted treatment failure. Those with treatment failure had a significantly lower rise in haemoglobin at 3 weeks compared with treatment successes (9.0 vs. 10.0 g/dl). Of the 76 parasite isolates collected before treatment, 40 (53%) were triple mutant DHFR-double DHPS (Tp-Db), the genotype most associated with SP resistance. Three weeks after SP treatment, the proportion of Tp-Db increased to 72% (31/43). The high treatment failure rate and proportion of parasites with Tp-Db negate the use of SP to shorten the course of quinine treatment in East Africa.