Outpacing the pneumococcus: Antibody dynamics in the first few days following pneumococcal capsular antigen stimulation

Children in developing countries are frequently exposed to the pneumococcus, but few develop invasive pneumococcal disease (IPD). We test the hypothesis that natural variation exists in the rapidity of IgG responses following exposure to pneumococcal polysaccharides, and that these differences are sufficiently great to affect susceptibility to and outcome of IPD. We recruited children aged 24-36 months, who had recovered from IPD, and age-matched healthy controls and vaccinated them with 1 dose of the 23-valent PPV to mimic natural exposure. We collected serum samples after vaccination and analysed the dynamics of anti-polysaccharide antibody responses to several capsular antigens. Mean IgG response times to different serotypes were 6.4-7.3 days, with standard deviations of 0.9-1.85 days, suggesting a natural range in response times of up to 7 days. Serotype 1 elicited the largest fold-rise, serotype 23F the smallest. The proportion of responses achieved by day 7 was similar in children with a history of IPD and healthy children. There was considerable natural variation in the rapidity of anti-capsular IgG responses extending over 4-7 days. There was no evidence to suggest that children who have experienced IPD respond more slowly to heterologous pneumococcal capsular antigens than do healthy children

Profile: The Kilifi Health and Demographic Surveillance System (KHDSS).

The Kilifi Health and Demographic Surveillance System (KHDSS), located on the Indian Ocean coast of Kenya, was established in 2000 as a record of births, pregnancies, migration events and deaths and is maintained by 4-monthly household visits. The study area was selected to capture the majority of patients admitted to Kilifi District Hospital. The KHDSS has 260 000 residents and the hospital admits 4400 paediatric patients and 3400 adult patients per year. At the hospital, morbidity events are linked in real time by a computer search of the population register. Linked surveillance was extended to KHDSS vaccine clinics in 2008. KHDSS data have been used to define the incidence of hospital presentation with childhood infectious diseases (e.g. rotavirus diarrhoea, pneumococcal disease), to test the association between genetic risk factors (e.g. thalassaemia and sickle cell disease) and infectious diseases, to define the community prevalence of chronic diseases (e.g. epilepsy), to evaluate access to health care and to calculate the operational effectiveness of major public health interventions (e.g. conjugate Haemophilus influenzae type b vaccine). Rapport with residents is maintained through an active programme of community engagement. A system of collaborative engagement exists for sharing data on survival, morbidity, socio-economic status and vaccine coverage

The role for osmotic agents in children with acute encephalopathies: a systematic review

Background: Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy.Methods: We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death.Results: We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.Conclusion: HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation

Geographic access to care is not a determinant of child mortality in a rural Kenyan setting with high health facility density

BACKGROUND: Policy-makers evaluating country progress towards the Millennium Development Goals also examine trends in health inequities. Distance to health facilities is a known determinant of health care utilization and may drive inequalities in health outcomes; we aimed to investigate its effects on childhood mortality. METHODS: The Epidemiological and Demographic Surveillance System in Kilifi District, Kenya, collects data on vital events and migrations in a population of 220,000 people. We used Geographic Information Systems to estimate pedestrian and vehicular travel times to hospitals and vaccine clinics and developed proportional-hazards models to evaluate the effects of travel time on mortality hazard in children less than 5 years of age, accounting for sex, ethnic group, maternal education, migrant status, rainfall and calendar time. RESULTS: In 2004-6, under-5 and under-1 mortality ratios were 65 and 46 per 1,000 live-births, respectively. Median pedestrian and vehicular travel times to hospital were 193 min (inter-quartile range: 125-267) and 49 min (32-72); analogous values for vaccine clinics were 47 (25-73) and 26 min (13-40). Infant and under-5 mortality varied two-fold across geographic locations, ranging from 34.5 to 61.9 per 1000 child-years and 8.8 to 18.1 per 1000, respectively. However, distance to health facilities was not associated with mortality. Hazard Ratios (HR) were 0.99 (95% CI 0.95-1.04) per hour and 1.01 (95% CI 0.95-1.08) per half-hour of pedestrian and vehicular travel to hospital, respectively, and 1.00 (95% CI 0.99-1.04) and 0.97 (95% CI 0.92-1.05) per quarter-hour of pedestrian and vehicular travel to vaccine clinics in children <5 years of age. CONCLUSIONS: Significant spatial variations in mortality were observed across the area, but were not correlated with distance to health facilities. We conclude that given the present density of health facilities in Kenya, geographic access to curative services does not influence population-level mortality

Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years

BACKGROUND: Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya. METHODS: Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates. RESULTS: Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90–0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010. CONCLUSION: Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission

Outpacing the pneumococcus: Antibody dynamics in the first few days following pneumococcal capsular antigen stimulation

Children in developing countries are frequently exposed to the pneumococcus, but few develop invasive pneumococcal disease (IPD). We test the hypothesis that natural variation exists in the rapidity of IgG responses following exposure to pneumococcal polysaccharides, and that these differences are sufficiently great to affect susceptibility to and outcome of IPD. We recruited children aged 24-36 months, who had recovered from IPD, and age-matched healthy controls and vaccinated them with 1 dose of the 23-valent PPV to mimic natural exposure. We collected serum samples after vaccination and analysed the dynamics of anti-polysaccharide antibody responses to several capsular antigens. Mean IgG response times to different serotypes were 6.4-7.3 days, with standard deviations of 0.9-1.85 days, suggesting a natural range in response times of up to 7 days. Serotype 1 elicited the largest fold-rise, serotype 23F the smallest. The proportion of responses achieved by day 7 was similar in children with a history of IPD and healthy children. There was considerable natural variation in the rapidity of anti-capsular IgG responses extending over 4-7 days. There was no evidence to suggest that children who have experienced IPD respond more slowly to heterologous pneumococcal capsular antigens than do healthy children

The impact of primary health care on malaria morbidity--defining access by disease burden.

OBJECTIVES: Primary care facilities are increasingly becoming the focal point for distribution of malaria intervention strategies, but physical access to these facilities may limit the extent to which communities can be reached. To investigate the impact of travel time to primary care on the incidence of hospitalized malaria episodes in a rural district in Kenya. METHODS: The incidence of hospitalized malaria in a population under continuous demographic surveillance was recorded over 3 years. The time to travel to the nearest primary health care facility was calculated for every child between birth and 5 years of age and trends in incidence of hospitalized malaria as a function of travel time were evaluated. RESULTS: The incidence of hospitalized malaria more than doubled as travel time to the nearest primary care facility increased from 10 min to 2 h. Good access to primary health facilities may reduce the burden of disease by as much as 66%. CONCLUSIONS: Our results highlight both the potential of the primary health care system in reaching those most at risk and reducing the disease burden. Insufficient access is an important risk factor, one that may be inequitably distributed to the poorest households

Biphasic clinical course among Kenyan children with cerebral malaria

Background: Cerebral malaria is the most severe neurological complication of Falciparum malaria. It is associated with a significant risk of death and neurological sequelae. A biphasic clinical picture is associated with an even greater risk of neurological sequelae. Objective: To examine the incidence and clinical characteristics of a biphasic clinical course in children with cerebral malaria and to study its relationship with outcome Method: We undertook a retrospective study of children admitted to Kilifi District Hospital with a history of impaired consciousness and Falciparum infection between January 1994 and December 2004. We identified children with a biphasic clinical course and examined their clinical characteristics and outcome against that of those with a single clinical course. Results: Out of 587 children with cerebral malaria, 11 were found to have a biphasic clinical course often heralded by recurrence of seizures. This clinical pattern was associated with a greater incidence of neurological sequelae but no death. Conclusion: We speculate that a biphasic clinical course may occur due to recurrent seizures, co-morbidity and reperfusion of cerebral areas previously clogged by parasitized red blood cells. A prospective examination of this group may shed more light on causality and enlighten further on pathogenesis of cerebral malaria. © 2002 African Journal of Neurological Sciences. All rights reserved

Incidence and clinical characteristics of group A rotavirus infections among children admitted to hospital in Kilifi, Kenya

Background: Rotavirus, predominantly of group A, is a major cause of severe diarrhoea worldwide, with the greatest burden falling on young children living in less-developed countries. Vaccines directed against this virus have shown promise in recent trials, and are undergoing effectiveness evaluation in sub-Saharan Africa. In this region limited childhood data are available on the incidence and clinical characteristics of severe group A rotavirus disease. Advocacy for vaccine intervention and interpretation of effectiveness following implementation will benefit from accurate base-line estimates of the incidence and severity of rotavirus paediatric admissions in relevant populations. The study objective was to accurately define the incidence and severity of group A rotavirus disease in a resource-poor setting necessary to make informed decisions on the need for vaccine prevention. Methods and Findings: Between 2002 and 2004 we conducted prospective surveillance for group A rotavirus infection at Kilifi District Hospital in coastal Kenya. Children , &lt; 13 y of age were eligible as ‘‘cases’’ if admitted with diarrhoea, and ‘‘controls’’ if admitted without diarrhoea. We calculated the incidence of hospital admission with group A rotavirus using data from a demographic surveillance study of 220,000 people in Kilifi District. Of 15,347 childhood admissions 3,296 (22%) had diarrhoea, 2,039 were tested for group A rotavirus antigen and, of these, 588 (29%) were positive. 372 (63%) rotavirus-positive cases were infants. Of 620 controls 19 (3.1%, 95% confidence interval [CI] 1.9–4.7) were rotavirus positive. The annual incidence (per 100,000 children) of rotavirus-positive admissions was 1,431 (95% CI 1,275–1,600) in infants and 478 (437–521) in under-5-y-olds, and highest proximal to the hospital. Compared to children with rotavirus-negative diarrhoea, rotavirus-positive cases were less likely to have coexisting illnesses and more likely to have acidosis (46% versus 17%) and severe electrolyte imbalance except hyponatraemia. In-hospital case fatality was 2% among rotavirus-positive and 9% among rotavirus-negative children. Conclusions: In Kilifi &gt; 2% of children are admitted to hospital with group A rotavirus diarrhoea in the first 5 y of life. This translates into over 28,000 vaccine-preventable hospitalisations per year across Kenya, and is likely to be a considerable underestimate. Group A rotavirus diarrhoea is associated with acute life-threatening metabolic derangement in otherwise healthy children. Although mortality is low in this clinical research setting this may not be generally true in African hospitals lacking rapid and appropriate management