Background

Most of the global neonatal deaths occur in developing nations, mostly in rural homes. Many of the newborns who receive formal medical care are treated in rural district hospitals and other peripheral health centres. However there are no published studies demonstrating trends in neonatal admissions and outcome in rural health care facilities in resource poor regions. Such information is critical in planning public health interventions. In this study we therefore aimed at describing the pattern of neonatal admissions to a Kenyan rural district hospital and their outcome over a 19 year period, examining clinical indicators of inpatient neonatal mortality and also trends in utilization of a rural hospital for deliveries.

Methods

Prospectively collected data on neonates is compared to non-neonatal paediatric (≤ 5 years old) admissions and deliveries' in the maternity unit at Kilifi District Hospital from January 1st 1990 up to December 31st 2008, to document the pattern of neonatal admissions, deliveries and changes in inpatient deaths. Trends were examined using time series models with likelihood ratios utilised to identify indicators of inpatient neonatal death.

Results

The proportion of neonatal admissions of the total paediatric ≤ 5 years admissions significantly increased from 11% in 1990 to 20% by 2008 (trend 0.83 (95% confidence interval 0.45 -1.21). Most of the increase in burden was from neonates born in hospital and very young neonates aged < 7days. Hospital deliveries also increased significantly. Clinical diagnoses of neonatal sepsis, prematurity, neonatal jaundice, neonatal encephalopathy, tetanus and neonatal meningitis accounted for over 75% of the inpatient neonatal admissions. Inpatient case fatality for all ≤ 5 years declined significantly over the 19 years. However, neonatal deaths comprised 33% of all inpatient death among children aged ≤ 5 years in 1990, this increased to 55% by 2008. Tetanus 256/390 (67%), prematurity 554/1,280(43%) and neonatal encephalopathy 253/778(33%) had the highest case fatality. A combination of six indicators: irregular respiration, oxygen saturation of <90%, pallor, neck stiffness, weight < 1.5 kg, and abnormally elevated blood glucose > 7 mmol/l predicted inpatient neonatal death with a sensitivity of 81% and a specificity of 68%.

Conclusions

There is clear evidence of increasing burden in neonatal admissions at a rural district hospital in contrast to reducing numbers of non-neonatal paediatrics' admissions aged ≤ 5years. Though the inpatient case fatality for all admissions aged ≤ 5 years declined significantly, neonates now comprise close to 60% of all inpatient deaths. Simple indicators may identify neonates at risk of death.

Summary

Background

The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region.

Methods

We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007–July 31, 2008); Agincourt, South Africa (Aug 4, 2008–Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009–Oct 30, 2009); Ifakara, Tanzania (May 4, 2009–Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010–April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centre's census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status.

Results

586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7·8 per 1000 people (95% CI 7·5–8·2) in Kilifi, 7·0 (6·2–7·4) in Agincourt, 10·3 (9·5–11·1) in Iganga-Mayuge, 14·8 (13·8–15·4) in Ifakara, and 10·1 (9·5–10·7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10·23, 95% CI 5·85–17·88; p<0·0001); abnormal antenatal periods (2·15, 1·53–3·02; p<0·0001); and head injury (1·97, 1·28–3·03; p=0·002). In adults (aged ≥18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2·28, 1·06–4·92; p=0·036), exposure to T canis (1·74, 1·27–2·40; p=0·0006), exposure to T gondii (1·39, 1·05–1·84; p=0·021), and exposure to O volvulus (2·23, 1·56–3·19; p<0·0001). Hypertension (2·13, 1·08–4·20; p=0·029) and exposure to T solium (7·03, 2·06–24·00; p=0·002) were risk factors for adult-onset disease.

Interpretation

The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region.

Funding

Wellcome Trust, University of the Witwatersrand, and South African Medical Research Council.

AIM

We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection.

METHOD

This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6–35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development.

RESULT

Using age-corrected psychomotor scores, a significant main effect of HIV status was observed (F(2,38.01)=7.89, p<0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome.

INTERPRETATION

Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa.

Background

In this study we aimed to assess site heterogeneity of early, intermediate, and late mortality prediction in children with severe Plasmodium falciparum malaria in sub-Saharan Africa.

Methods

Medical records of 26,036 children admitted with severe Plasmodium falciparum malaria in six hospital research centers between December 2000 to May 2005 were analyzed. Demographic, clinical and laboratory data of children who died within 24 hours (early), between 24 and 47 hours (intermediate) and thereafter (48 hours or later, late mortality) were compared between groups and survivors.

Results

Overall mortality was 4·3% (N = 1,129). Median time to death varied across sites (P<0·001), ranging from 8h (3h–52h) in Lambaréné to 40h (10h–100h) in Kilifi. Fifty-eight percent of deaths occurred within 24 hours and intermediate and late mortality rate were 19% and 23%, respectively. Combining all sites, deep breathing, prostration and hypoglycemia were independent predictors for early, intermediate and late mortality (P<0·01). Site specific independent predictors for early death included prostration, coma and deep breathing at all sites (P<0·001). Site specific independent predictors for intermediate and late death largely varied between sites (P<0·001) and included between 1 and 7 different clinical and laboratory variables.

Conclusion

Site heterogeneity for mortality prediction is evident in African children with severe malaria. Prediction for early mortality has the highest consistency between sites.

In many developing countries, people with epilepsy do not receive appropriate treatment for their condition, a phenomenon called the treatment gap (TG). We carried out a systematic review to investigate the magnitude, causes and intervention strategies to improve outcomes in developing countries. We systematically searched MEDLINE, EMBASE and PsycINFO databases, supplemented by a hand search of references in the key papers. The degree of heterogeneity and a pooled TG estimate were determined using meta-analysis techniques. The estimates were further stratified by continent and location of study (urban, rural). Twenty-seven studies met the inclusion criteria: twelve from Africa, nine from Asia and six from Latin America. We observed a high degree of heterogeneity and inconsistency between studies. The overall estimate of the TG was 56/100 (95% CI: 31.1-100.0). The variation in estimates could possibly be explained by non-uniform TG estimation methods and the diverse study populations, among other factors. The TG was mainly attributed to inadequate skilled manpower, cost of treatment, cultural beliefs and unavailability of anti-epileptic drugs (AEDs). These factors have been addressed using different intervention strategies for instance education and supply of AEDs. Future research should estimate the TG coherently and develop sustainable interventions that will address the causes.

Many people with epilepsy (PWE) in resource‐poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision.

Highlights

► Many with epilepsy do not receive appropriate treatment; epilepsy treatment gap (ETG). ► Qualitative study exploring reasons for ETG and identifying viable interventions in Kenya. ► ETG can be addressed through development of multifaceted interventions.

PfEMP1 is a family of cytoadhesive surface antigens expressed on erythrocytes infected with Plasmodium falciparum, the parasite that causes the most severe form of malaria. These surface antigens play a role in immune evasion and are thought to contribute to the pathogenesis of the malaria parasite. Previous studies have suggested a role for a specific subset of PfEMP1 called “group A” in severe malaria. To explore the role of group A PfEMP1 in disease, we measured the expression of the “var” genes that encode them in parasites from clinical isolates collected from children suffering from malaria. We also looked at the ability of these clinical isolates to induce rosetting of erythrocytes, which indicates a cytoadhesion phenotype that is thought to be important in pathogenesis. These two sets of data were correlated with the presence of two life-threatening manifestations of severe malaria in the children: impaired consciousness and respiratory distress. Using regression analysis, we show that marked rosetting was associated with respiratory distress, whereas elevated expression of group A-like var genes without elevated rosetting was associated with impaired consciousness. The results suggest that manifestations of malarial disease may reflect the distribution of cytoadhesion phenotypes expressed by the infecting parasite population.

Both helminthiases and epilepsy occur globally, and are particularly prevalent in developing regions of the world. Studies have suggested an association between epilepsy and helminth infection, but a causal relationship is not established in many helminths, except perhaps with neurocysticercosis. We review the available literature on the global burden of helminths, and the epidemiological evidence linking helminths to epilepsy. We discuss possible routes that helminths affect the central nervous system of humans and the immunological response to helminth infection in the central nervous system, looking at possible mechanisms of epileptogenesis. Finally, we discuss the current gaps in knowledge about the interaction between helminths and epilepsy.

Summary

Background

Many people with epilepsy in low-income countries do not receive appropriate biomedical treatment. This epilepsy treatment gap might be caused by patients not seeking biomedical treatment or not adhering to prescribed antiepileptic drugs (AEDs). We measured the prevalence of and investigated risk factors for the epilepsy treatment gap in rural Kenya.

Methods

All people with active convulsive epilepsy identified during a cross-sectional survey of 232 176 people in Kilifi were approached. The epilepsy treatment gap was defined as the percentage of people with active epilepsy who had not accessed biomedical services or who were not on treatment or were on inadequate treatment. Information about risk factors was obtained through a questionnaire-based interview of sociodemographic characteristics, socioeconomic status, access to health facilities, seizures, stigma, and beliefs and attitudes about epilepsy. The factors associated with people not seeking biomedical treatment and not adhering to AEDs were investigated separately, adjusted for age.

Findings

673 people with epilepsy were interviewed, of whom 499 (74%) reported seeking treatment from a health facility. Blood samples were taken from 502 (75%) people, of whom 132 (26%) reported taking AEDs, but 189 (38%) had AEDs detectable in the blood. The sensitivity and specificity of self-reported adherence compared with AEDs detected in blood were 38·1% (95% CI 31·1–45·4) and 80·8% (76·0–85·0). The epilepsy treatment gap was 62·4% (58·1–66·6). In multivariable analysis, failure to seek biomedical treatment was associated with a patient holding traditional animistic religious beliefs (adjusted odds ratio 1·85, 95% CI 1·11–2·71), reporting negative attitudes about biomedical treatment (0·86, 0·78–0·95), living more than 30 km from health facilities (3·89, 1·77–8·51), paying for AEDs (2·99, 1·82–4·92), having learning difficulties (2·30, 1·29–4·11), having had epilepsy for longer than 10 years (4·60, 2·07–10·23), and having focal seizures (2·28, 1·50–3·47). Reduced adherence was associated with negative attitudes about epilepsy (1·10, 1·03–1·18) and taking of AEDs for longer than 5 years (3·78, 1·79–7·98).

Interpretation

The sensitivity and specificity of self-reported adherence is poor, but on the basis of AED detection in blood almost two-thirds of patients with epilepsy were not on treatment. Education about epilepsy and making AEDs freely available in health facilities near people with epilepsy should be investigated as potential ways to reduce the epilepsy treatment gap.

Funding

Wellcome Trust.

Epilepsy remains misunderstood, particularly in resource poor countries (RPC). We developed and validated a tool to assess beliefs and attitudes about epilepsy among people with epilepsy (PWE) in Kilifi, Kenya. The 50-item scale was developed through a literature review and qualitative study findings, and its reliability and validity were assessed with 673 PWE. A final scale of 34 items had Cronbach's alpha scores for the five subscales: causes of epilepsy (α = 0.71); biomedical treatment of epilepsy (α = 0.70); cultural treatment of epilepsy (α = 0.75); risk and safety concerns about epilepsy (α = 0.56); and negative attitudes about epilepsy (α = 0.76) and entire scale (α = 0.70). Test–retest reliability was acceptable for all the subscales.

The Kilifi Epilepsy Beliefs and Attitude Scale is a reliable and valid tool that measures beliefs and attitudes about epilepsy. It may be useful in other RPC or as a tool to assess the effectiveness of interventions to improve knowledge, beliefs, and attitudes about epilepsy.

Highlights

► Kilifi Epilepsy Beliefs and Attitude Scale was developed for use in Africa. ► The scale consists of 34 items in 5 subscales. ► The scale has excellent psychometric properties.

Background

Bacterial sepsis is thought to be a major cause of young infant deaths in low income countries, but there are few precise estimates of its burden or causes. We studied invasive bacterial infections (IBI) in young infants, born at home or in first level health units (“outborn”) who were admitted to a Kenyan rural district hospital during an 8-year period.

Methods

Clinical and microbiologic data from admission blood cultures and cerebrospinal fluid cultures on all outborn infants aged less than 60 days admitted from 2001 through 2009, were examined to determine etiology of IBI and antimicrobial susceptibilities.

Results

Of the 4,467 outborn young infants admitted, 748 (17%) died. Five hundred and five (11%) had IBI (10% bacteremia,3% bacterial meningitis), with a case fatality of 33%. The commonest organisms were Klebsiella spp., Staphylococcus aureus, Streptococcus pneumoniae, Group B Streptococcus, Acinetobacter spp., Escherichia coli and Group A Streptococcus. Notably, some blood culture isolates were seen in outborn neonates in the first week of life, but not in inborns: Salmonella, Aeromonas and Vibrio spp. Eighty-one percent of isolates were susceptible to penicillin and/or gentamicin and 84% to ampicillin and/or gentamicin. There was a trend to increasing in vitro antimicrobial resistance to these combinations from 2008 but without a worse outcome.

Conclusions

IBI is common in outborn young infants admitted to rural African hospitals with a high mortality. Presumptive antimicrobial use is justified for all young infants admitted to hospital.

The aim of this study was to develop and validate a tool to measure perceived stigma among people with epilepsy (PWE) in Kilifi, Kenya. We reviewed existing scales that measured stigma, particularly of epilepsy. We conducted a qualitative study to determine salient concerns related to stigma in Kilifi. Themes were generated, and those related to stigma were used to construct an 18-item stigma scale. A descriptive cross-sectional survey was then conducted among 673 PWE to assess the reliability and validity of the scale. Internal consistency was calculated using Cronbach's alpha and test–retest reliability with an interclass correlation coefficient. The final scale had 15 items, which had high internal consistency (Cronbach's α = 0.91) and excellent test–retest reliability (r = 0.92). Factor analysis indicated that the scale was unidimensional with one factor solution explaining 45.8% of the variance. The Kilifi Stigma Scale for Epilepsy is a culturally appropriate measure of stigma with strong psychometric properties.

Highlights

► We developed and validated a scale to measure perceived stigma in epilepsy. ► The scale was unidimensional: one factor solution explained 45.8% of the variance.► It had high internal consistency and excellent test-retest reliability. ► It can be adapted and validated for use in other research settings.

The aims of this study were to record behavioral problems in children with epilepsy (CWE), compare the prevalence with that reported among healthy children without epilepsy, and investigate the risk factors. A child behavioral questionnaire for parents comprising 15 items was administered to the main caregiver of 108 CWE and 108 controls matched for age in Kilifi, Kenya. CWE had a higher mean score for reported behavioral problems than controls (6.9 vs 4.9, t = 4.7, P < 0.001). CWE with active epilepsy also recorded more behavioral problems than those with inactive epilepsy (8.2 vs 6.2, t = − 2.9, P = 0.005). A significantly greater proportion of CWE (49% vs 26% of controls) were reported to have behavioral problems. Active epilepsy, cognitive impairment, and focal seizures were the most significant independent covariates of behavioral problems. Behavioral problems in African CWE are common and need to be taken into consideration in planning comprehensive clinical services in this region.

Highlights

► Behavioral problems in children with epilepsy were studied. ► Behavioral problems were reported in 49% of children with epilepsy and in 26% of the controls. ► Active epilepsy type, cognitive impairment, and focal seizures predicted behavioral problems. ► Behavioral problems are common in children with epilepsy and need to be considered in planning clinical services.

Purpose

Epilepsy is common in sub-Saharan Africa but is poorly characterized. Most studies are hospital-based, and may not reflect the situation in rural areas with limited access to medical care. We examined people with active convulsive epilepsy (ACE), to determine if the clinical features could help elucidate the causes.

Methods

We conducted a detailed descriptive analysis of 445 people with ACE identified through a community-based survey of 151,408 people in rural Kenya, including the examination of electroencephalograms.

Results

Approximately half of the 445 people with ACE were children or adolescents. Seizures began in childhood in 78% of those diagnosed. An episode of status epilepticus was recalled by 36% cases, with an episode of status epilepticus precipitated by fever in 26%. Overall 169 had an abnormal electroencephalogram, 29% had focal features, 34% had epileptiform activity. In the 146 individuals who reported generalised tonic-clonic seizures only, 22% had focal features on their electroencephalogram. Overall 71% of patients with ACE had evidence of focal abnormality, documented by partial onset seizures, focal neurological deficits or focal abnormalities on the electroencephalogram. Increased seizure frequency was strongly associated with age and cognitive impairment in all ages and non-attendance at school in children (p < 0.01).

Discussion

Children and adolescents bear the brunt of epilepsy in a rural population in Africa. The predominance of focal features and the high proportion of patients with status epilepticus, suggests that much of the epilepsy in this region has identifiable causes, many of which could be prevented.

Background

Surveys have been the conventional methods used for identification of people with disabilities; however, they have been observed to be expensive and time-consuming that may not be affordable or practical. As a result, the participatory rural appraisal (PRA) and key informant (KI) approaches have been developed and increasingly used in the resource-poor countries.

Objective

To investigate the strengths and weaknesses of PRA and KI approaches in the identification of people with disability in resource-poor countries.

Method

A review of published related papers was performed by searching electronic databases including PubMed, Scirus, Health on the Net (HON), Ovid Medline and SOURCE disability database.

Results

A total of 11 relevant papers were identified from the literature that used PRA or KI methods or both. The PRA and KI approaches were not only consistently less expensive than conventional surveys, but also observed to be simple and fast for identifying disabilities according to local perceptions, although they were less sensitive. The evidence showed that PRA and KI processes had the benefit of engaging and developing long-term partnerships with the local communities and so the likelihood of positive long-term impact on the community.

Conclusions

The PRA and KI approaches could be fast and cost-effective methods for identifying people with disabilities as an alternative to surveys. They are especially useful when identification is related to subsequent development of community-based services for persons with disabilities. However, surveys were shown to be more sensitive and therefore more accurate for establishing prevalence rates of impairment.

Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area.

Plasmodium falciparum is the most common parasitic infection of the central nervous system causing neuro-cognitive deficits in 5–26% of paediatric cases. The burden cannot be reliably estimated because of lack of sensitive, culture-fair and robust assessments in rural settings. Auditory and visual brain event related potentials (ERPs) are used to compare novelty processing in children exposed to severe malaria with community controls. Fifty children previously admitted and discharged from Kilifi District Hospital with severe falciparum malaria were selected and compared with 77 unexposed agematched children. The results showed that up to 14% of children exposed to severe malaria had significantly different responses to novelty compared to unexposed children. Children exposed to severe malaria had smaller P3a amplitudes to novelty in both auditory [F (3, 119) = 4.545, p = 0.005] and visual [F (3, 119) = 6.708, p < 0.001] paradigms compared to unexposed children. In the auditory domain the differences in processing of novelty were not related to early component processing. The percentage of children with severe malaria showing impaired performance using ERPs is within the range previously reported using neuropsychological tests. The overall pattern suggests that severe malaria affects prefrontal and temporal cortices normally activated by stimulus novelty.

Malaria is a major public health problem in the developing world owing to its high rates of morbidity and mortality. Of all the malarial parasites that infect humans, Plasmodium falciparum is most commonly associated with neurological complications, which manifest as agitation, psychosis, seizures, impaired consciousness and coma (cerebral malaria). Cerebral malaria is the most severe neurological complication; the condition is associated with mortality of 15–20%, and a substantial proportion of individuals with this condition develop neurocognitive sequelae. In this Review, we describe the various neurological complications encountered in malaria, discuss the underlying pathogenesis, and outline current management strategies for these complications. Furthermore, we discuss the role of adjunctive therapies in improving outcome.

Maternal and child health are high priorities for international development. Through a Review of published work, we show substantial gaps in current knowledge on incidence (cases per live births), aetiology, and risk factors for both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. Although existing published data suggest that sepsis causes about 10% of all maternal deaths and 26% of neonatal deaths, these are likely to be considerable underestimates because of methodological limitations. Successful intervention strategies in resource-rich settings and early studies in sub-Saharan Africa suggest that the burden of maternal and early onset neonatal bacterial sepsis could be reduced through simple interventions, including antiseptic and antibiotic treatment. An effective way to expedite evidence to guide interventions and determine the incidence, aetiology, and risk factors for sepsis in sub-Saharan Africa would be through a multiarmed factorial intervention trial aimed at reducing both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa.

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.

Background

During acute Human parvovirus B19 (B19) infection a transient reduction in blood haemoglobin concentration is induced, due to a 5-7 day cessation of red cell production. This can precipitate severe anaemia in subjects with a range of pre-existing conditions. Of the disease markers that occur during B19 infection, high IgM levels occur closest in time to the maximum reduction in haemoglobin concentration. Previous studies of the contribution of B19 to severe anaemia among young children in Africa have yielded varied results. This retrospective case/control study seeks to ascertain the proportion of severe anaemia cases precipitated by B19 among young children admitted to a Kenyan district hospital.

Methods

Archival blood samples from 264 children under 6 years with severe anaemia admitted to a Kenyan District Hospital, between 1999 and 2004, and 264 matched controls, were tested for B19 IgM by Enzyme Immunosorbent Assay and 198 of these pairs were tested for B19 DNA by PCR. 536 samples were also tested for the presence of B19 IgG.

Results

7 (2.7%) cases and 0 (0%) controls had high B19 IgM levels (Optical Density > 5 × cut-off value) (McNemar's exact test p = 0.01563), indicating a significant association with severe anaemia. The majority of strongly IgM positive cases occurred in 2003.

10/264 (3.7%) cases compared to 5/264 (1.9%) controls tested positive for B19 IgM. This difference was not statistically significant, odds ratio (OR) = 2.00 (CI95 [0.62, 6.06], McNemar's exact test p = 0.3018. There was no significant difference between cases and controls in the B19 IgG (35 (14.8%) vs 32 (13.6%)), OR = 1.103 (CI95 [0.66, 1.89], McNemar's exact test, p = 0.7982), or the detection of the B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2 (CI95 [0.33, 4.01], McNemar's exact test p = 1).

Conclusions

High B19 IgM levels were significantly associated with severe anaemia, being found only among the cases. This suggests that 7/264 (2.7%) of cases of severe anaemia in the population of children admitted to KDH were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data that shows that less than 15% of children in the study were exposed to B19, a figure much lower than reported in other tropical areas.

Objective

The aim of this study was to describe the normative development of the electrophysiological response to auditory and visual novelty in children living in rural Kenya.

Methods

We examined event-related potentials (ERPs) elicited by novel auditory and visual stimuli in 178 normally-developing children aged 4–12 years (86 boys, mean 6.7 years, SD 1.8 years and 92 girls, mean 6.6 years, SD 1.5 years) who were living in rural Kenya.

Results

The latency of early components (auditory P1 and visual N170) decreased with age and their amplitudes also tended to decrease with age. The changes in longer-latency components (Auditory N2, P3a and visual Nc, P3a) were more modality-specific; the N2 amplitude to novel stimuli decreased with age and the auditory P3a increased in both latency and amplitude with age. The Nc amplitude decreased with age while visual P3a amplitude tended to increase, though not linearly.

Conclusions

The changes in the timing and magnitude of early-latency ERPs likely reflect brain maturational processes. The age-related changes to auditory stimuli generally occurred later than those to visual stimuli suggesting that visual processing matures faster than auditory processing.

Significance

ERPs may be used to assess children’s cognitive development in rural areas of Africa.

Approximately 280 000 children are born with sickle cell anemia (SCA) in Africa annually, yet few survive beyond childhood. Falciparum malaria is considered a significant cause of this mortality. We conducted a 5-year prospective surveillance study for malaria parasitemia, clinical malaria, and severe malarial anemia (SMA) in Dar-es-Salaam, Tanzania, between 2004 and 2009. We recorded 10 491 visits to the outpatient clinic among 1808 patients with SCA and 773 visits among 679 patients without SCA. Similarly, we recorded 691 hospital admissions among 497 patients with SCA and 2017 in patients without SCA. Overall, the prevalence of parasitemia was lower in patients with SCA than in patients without SCA both at clinic (0.7% vs 1.6%; OR, 0.53; 95% CI, 0.32-0.86; P = .008) and during hospitalization (3.0% vs 5.6%; OR, 0.46; 95% CI, 0.25-0.94; P = .01). Furthermore, patients with SCA had higher rates of malaria during hospitalization than at clinic, the ORs being 4.29 (95% CI, 2.63-7.01; P < .001) for parasitemia, 17.66 (95% CI, 5.92-52.71; P < .001) for clinical malaria, and 21.11 (95% CI, 8.46-52.67; P < .001) for SMA. Although malaria was rare among patients with SCA, parasitemia during hospitalization was associated with both severe anemia and death. Effective treatment for malaria during severe illness episodes and further studies to determine the role chemoprophylaxis are required.