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OBJECTIVE: To investigate whether the outpatient, syndrome-based approach of the Integrated Management of Childhood Illness (IMCI) protocol could be extended to the inpatient arena to give clear and simple minimum standards of care for poorly resourced facilities. METHODS: A prospective, one-year admission cohort retrospectively compared hypothetical performance of syndrome-based management with paediatrician-defined final diagnosis. Admission syndrome definitions were based on local adaptations to the IMCI protocol that encompassed 20 clinical features, measurement of oxygen saturation, and malaria microscopy. FINDINGS: After 315 children with clinically obvious diagnoses (e.g. sickle cell disease and burns) were excluded, 3705 admission episodes were studied. Of these, 2334 (63%) met criteria for at least one severe syndrome (mortality 8% vs 95%) for severe pneumonia, severe malaria, and diarrhoea with severe dehydration, and probably for severe malnutrition (sensitivity 71%). Syndrome-directed treatment suggested the use of broad-spectrum antibiotics in 75/133 (56% sensitivity) children with bacteraemic and 63/71 (89% sensitivity) children with meningitis. CONCLUSIONS: Twenty clinical features, oxygen saturation measurements, and results of malaria blood slides could be used for inpatient, syndrome-based management of acute paediatric admissions. The addition of microscopy of the cerebrospinal fluid and haemoglobin measurements would improve syndrome-directed treatment considerably. This approach might rationalize admission policy and standardize inpatient paediatric care in resource-poor countries, although the clinical detection of bacteraemia remains a problem.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of immune targets, which play a central role in the host--parasite interaction by binding to various host molecules. They are encoded by a diverse family of genes called var, of which there are [approximately equal to]60 copies in each parasite genome. In sub-Saharan Africa, although P. falciparum infection occurs throughout life, severe malarial disease tends to occur only in childhood. This could potentially be explained if (i) PfEMP1 variants differ in their capacity to support pathogenesis of severe malaria and (ii) this capacity is linked to the likelihood of each molecule being recognized and cleared by naturally acquired antibodies. Here, in a study of 217 Kenyan children with malaria, we show that expression of a group of var genes 'cys2,' containing a distinct pattern of cysteine residues, is associated with low host immunity. Expression of cys2 genes was associated with parasites from young children, those with severe malaria, and those with a poorly developed antibody response to parasite-infected erythrocyte surface antigens. Cys-2 var genes form a minor component of all genomic var repertoires analyzed to date. Therefore, the results are compatible with the hypothesis that the genomic var gene repertoire is organized such that PfEMP1 molecules that confer the most virulence to the parasite tend also to be those that are most susceptible to the development of host immunity. This may help the parasite to adapt effectively to the development of host antibodies through modification of the host--parasite relationship. antigenic variation | escape | malaria | PfEMP1 | virulence doi/10.1073/pnas.0907590106

Objective To describe the prevalence of hypoxaemia in children admitted to a hospital in Kenya for the purpose of identifying clinical signs of hypoxaemia for emergency triage assessment, and to test the hypothesis that such signs lead to correct identification of hypoxaemia in children, irrespective of their diagnosis. Methods From 2002 to 2005 we prospectively collected clinical data and pulse oximetry measurements for all paediatric admissions to Kilifi District Hospital, Kenya, irrespective of diagnosis, and assessed the prevalence of hypoxaemia in relation to the WHO clinical syndromes of "pneumonia" on admission and the final diagnoses made at discharge. We used the data collected over the first three years to derive signs predictive of hypoxaemia, and data from the fourth year to validate those signs. Findings Hypoxaemia was found in 977 of 15 289 (6.4%) of all admissions (5% to 19% depending on age group) and was strongly associated with inpatient mortality (age-adjusted risk ratio: 4.5; 95% confidence interval, CI: 3.8-5.3). Although most hypoxaemic children aged [greater than or equal to] 60 days met the WHO criteria for a syndrome of "pneumonia" on admission, only 215 of the 693 (31%) such children had a final diagnosis of lower respiratory tract infection (LRTI). The most predictive signs for hypoxaemia included shock, a heart rate < 80 beats per minute, irregular breathing, a respiratory rate > 60 breaths per minute and impaired consciousness. However, 5-15% of the children who had hypoxaemia on admission were missed, and 18% of the children were incorrectly identified as hypoxaemic. Conclusion The syndromes of pneumonia make it possible to identify most hypoxaemic children, including those without LRTI. Shock, bradycardia and irregular breathing are important predictive signs, and severe malaria with respiratory distress is a common cause of hypoxaemia. Overall, however, clinical signs are poor predictors of hypoxaemia, and using pulse oximetry in resource-poor health facilities to target oxygen therapy is likely to save costs. Objectif Decrire la prevalence de l&apos;hypoxemie chez les enfants admis dans un hopital kenyan en vue d&apos;identifier les signes cliniques de l&apos;hypoxemie utilisables pour l&apos;evaluation dans le cadre du triage d&apos;urgence et tester l&apos;hypothese selon laquelle ces signes permettraient une identification correcte des enfants atteints d&apos;hypoxemie, independamment du diagnostic qui doit leur etre affecte. Methodes De 2002 a 2005, nous avons recueilli prospectivement des donnees cliniques et des mesures par oxymetrie pulsee pour l&apos;ensemble des admissions pediatriques a l&apos;hopital de district de Kilifi au Kenya, independamment du diagnostic concernant ces enfants, et evalue la prevalence de l&apos;hypoxemie en relation avec la presence d&apos;un syndrome clinique de type pneumonie selon l&apos;OMS lors de l&apos;admission et du diagnostic final de sortie. Nous avons utilise les donnees collectees sur les trois premieres annees pour determiner les signes predictifs de l&apos;hypoxemie et les donnees de la quatrieme annee pour valider ces signes. Resultats Nous avons releve une hypoxemie chez 977 des 15289 enfants hospitalises (soit 6,4 %, chiffre variant entre 5 a 19 % selon la tranche d&apos;age) et une association forte entre hypoxemie et mortalite des patients hospitalises (rapport de risques ajuste selon l&apos;age: 4,5; intervalle de confiance a 95 %, IC: 3,8-5,3). Si la plupart des enfants hypoxemiques de 60 jours et plus remplissaient, lors de leur admission, les criteres OMS de definition du syndrome de type pneumonie, seuls 215 ales 693 enfants hypoxemiques de 60 jours et plus (31%) ont finalement ete diagnostiques comme atteints d&apos;une infection des voies respiratoires inferieures (IVRI). Parmi les signes les plus predictifs de l&apos;hypoxemie figuraient l&apos;etat de choc, une frequence cardiaque inferieure a 80 battements par minute, une respiration irreguliere, une frequence respiratoire superieure a 60 respirations par minute et un etat de conscience alteree. Neanmoins, 5 a 15 % des enfants hypoxemiques Iors de leur admission n&apos;ont pas ete reperes et 18 % des enfants ont ete identifies a tort comme hypoxemiques. Conclusion Le recours au syndrome de type pneumonie permet d&apos;identifier la plupart des enfants hypoxemiques, y compris ceux atteints d&apos;une IVRI. l&apos;etat de choc, la bradycardie et l&apos;irregularite respiratoire sont des signes predictifs importants et le paludisme grave, avec detresse respiratoire, est une cause courante d&apos;hypoxemie. Globalement neanmoins, les signes cliniques n&apos;ont pas une grande valeur predictive pour l&apos;hypoxemie et li est probable que l&apos;utilisation de l&apos;oxymetrie pulsee par les etablissements de soins qui manquent de moyens pour identifier les patients devant beneficier d&apos;un traitement par l&apos;oxygene permettra de realiser des economies. Objetivo Describir la prevalencia de hipoxemia en ninos ingresados en un hospital de Kenya a fin de identificar los signos clinicos de la misma para un triaje de emergencia, y contrastar la hipotesis de que esos signos permiten detectar correctamente la hipoxemia en los ninos, independientemente del diagnostico. Metodos Entre 2002 y 2005 se reunieron prospectivamente datos clinicos y de oximetria de pulso para todos los ingresos pediatricos en el Hospital de Distrito de Kilifi, Kenya, con independencia del diagnostico, determinandose la prevalencia de hipoxemia en relacion con el sindrome clinico de << neumonia >> definido por la OMS en el momento del ingreso y con el diagnostico final en el momento del alta. Los datos recogidos durante los tres primeros anos se usaron para determinar los signos predictivos de hipoxemia, y los datos reunidos a partir del cuarto ano fueron utilizados para validar esos signos. Resultados Se detecto hipoxemia en 977 de 15 289 (6,4%) ninos ingresados (5%-19% segun el grupo de edad), muy estrechamente asociada a mortalidad hospitalaria (razon de riesgos ajustada por edad: 4,5; intervalo de confianza [IC] del 95%: 3,8-5,3). Aunque la mayoria de los ninos hipoxemicos con [mayor que o igual a] 60 dias de edad cumplian los criterios de la OMS para que pudiera diagnosticarse un sindrome de <> en el momento del ingreso, solo 215 de los 693 (31%) ninos hipoxemicos de esa edad recibieron un diagnostico final de infeccion de las vias respiratorias inferiores (IVRI). Los signos mas predictivos de hipoxemia fueron el choque, una frecuencia cardiaca < 80 latidos por minuto, una respiracion irregular, una frecuencia respiratoria > 60 respiraciones por minuto y un deterioro de la conciencia. Sin embargo, no se detecto la hipoxemia en un 5%-15% de los ninos que la sufrian en el momento del ingreso, y un 18% de los ninos fueron considerados hipoxemicos incorrectamente. Conclusion Los sindromes de neumonia permiten identificar a la mayoria de los ninos hipoxemicos, incluidos los que no presentan IVRI. Un cuadro de choque, la bradicardia y una respiracion irregular son signos predictivos importantes, y la malaria grave con distres respiratorio es una causa comun de hipoxemia. Sin embargo, en general los signos clinicos son poco fiables como factores predictivos de la hipoxemia, y es probable que, en los servicios de salud con recursos escasos, el uso de la oximetria de pulso como criterio para aplicar oxigenoterapia permita ahorrar costos., Introduction Recognizing and correcting poor oxygenation early is an essential aspect of paediatric emergency care. The management of hypoxaemia includes establishing an open airway and alveolar ventilatjon, providing supplemental oxygen, [...]

Cerebral malaria (CM) in children is associated with a high mortality and long-term neurocognitive sequelae. Both erythropoietin (Epo) and vascular endothelial growth factor (VEGF) have been shown to be neuroprotective. We hypothesized that high plasma and cerebrospinal fluid (CSF) levels of these cytokines would prevent neurological sequelae in children with CM. We measured Epo, VEGF, and tumor necrosis factor in paired samples of plasma and CSF of Kenyan children admitted with CM. Logistic regression models were used to identify risk and protective factors associated with the development of neurological sequelae. Children with CM (n = 124) were categorized into three groups: 76 without sequelae, 32 with sequelae, and 16 who died. Conditional logistic regression analysis matching the 32 patients with CM and neurological sequelae to 64 patients with CM without sequelae stratified for hemoglobin level estimated that plasma Epo (>200 units/liter) was associated with >80% reduction in the risk of developing neurological sequelae [adjusted odds ratio (OR) 0.18; 95% C.I. 0.05-0.93; P = 0.041]. Admission with profound coma (adjusted OR 5.47; 95% C.I. 1.45-20.67; P = 0.012) and convulsions after admission (adjusted OR 16.35; 95% C.I. 2.94-90.79; P = 0.001) were also independently associated with neurological sequelae. High levels of Epo were associated with reduced risk of neurological sequelae in children with CM. The age-dependent Epo response to anemia and the age-dependent protective effect may influence the clinical epidemiology of CM. These data support further study of Epo as an adjuvant therapy in CM. anemia | Plasmodium falciparum | severe malaria | vascular endothelial growth factor

ABSTRACT Background Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for [...]

ABSTRACT Background With strict adherence to international recommended treatment guidelines, the case fatality for severe malnutrition ought to be less than 5%. In African hospitals, fatality rates of 20% are [...]

Clinical, microbiological and epidemiologic surveillance mechanisms are used to define invasive Haemophilus influenzae type b (Hib) disease incidence and to evaluate Hib conjugate vaccine program effectiveness in Kenya. It is found that introduction of Hib vaccine into the routine childhood immunization program reduces Hib disease incidence among children younger than 5 years to 12% of its baseline level, the impact not being observed until the third year after vaccine introduction.