Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

ObjectivesTo evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer''s disease and dementia.DesignThree year population based cohort study.SettingKungsholmen cohort, Stockholm, Sweden.Participants1435 people aged 75-95 years without dementia.AssessmentsSingle question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.ResultsNone of the three instruments was sufficiently predictive of Alzheimer''s disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer''s disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.ConclusionThis three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.

What is already known on this topic

Alzheimer''s disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer''s disease and dementia

What this study adds

This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer''s disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer''s disease and dementia do not report problems with their memory three years before diagnosis     

Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study

Objectives: To determine the prevalence of the pathogenic strain of Neisseria meningitidis in contacts of patients with meningococcal disease, and to determine which contact groups are likely to be carriers and warrant chemoprophylaxis. Design: Population based study. Setting: Norwegian county of Telemark. Subjects: 1535 primary contacts of 48 patients with meningococcal disease, and 78 secondary contacts. Interventions: Carriers of the pathogenic strain were treated with rifampicin. All household members and kissing contacts under 15 years of age were treated with oral penicillin. Contacts were taught to recognise the symptoms of meningococcal disease. Results: In 27 of 48 cases investigated, contacts carrying the pathogenic strain of N meningitidis were found. A total of 42 such contacts were identified. Contacts were stratified into three classes according to the assumed closeness of contact with patients. In class 1 (household members and kissing contacts) the prevalence of the pathogenic strain was 12.4% (95% confidence interval 5.5% to 19.3%). In classes 2 and 3 the prevalence was 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%). Conclusions: There is a high rate of carriage of the pathogenic strain of N meningitidis in patients’ household members and kissing contacts, and this supports the practice of giving chemoprophylaxis to these contacts. The prevalence of carriage among other contacts is 2-3 times that found in the general population (0.7%); the benefits of chemoprophylaxis to these contacts may be marginal.

Key messages

• Contacts of patients with meningococcal disease have a 12.4% (95% confidence interval 5.5% to 19.3%) risk of carrying the pathogenic meningococcus if they are kissing contacts or household members
• The risk of carriage of the pathogenic strain for two groups of contacts less close than household members or kissing contacts is 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%)

     

Risk of neurological diseases among survivors of electric shocks: a nationwide cohort study, Denmark, 1968-2008

Several studies suggest a link between electric injuries and neurological diseases, where electric shocks may explain elevated risks for neuronal degeneration and, subsequently, neurological diseases. We conducted a retrospective cohort study on the risk of neurological diseases among people in Denmark who had survived an electric accident in 1968-2008. The cohort included 3,133 people and occurrences of neurological diseases were determined by linkage to the nationwide population-based Danish National Register of Patients. The numbers of cases observed at first hospital contact in the cohort were compared with the respective rates of first hospital contacts for neurological diseases in the general population. We observed significantly increased risks for peripheral nerve diseases (standardized hospitalization ratio (SHR), 1.66; 95% confidence interval (CI), 1.22-2.22), for migraine (SHR, 1.80; 95% CI, 1.23-2.54), for vertigo (SHR, 1.60; 95% CI, 1.22-2.05), and for epilepsy (SHR, 1.45; 95% CI, 1.11-1.85). Only small numbers of cases of other neurological diseases were found, making the risk estimates unstable. These findings suggest an association between a single electric shock and increased risks for peripheral nerve diseases, migraines, vertigo, and epilepsy, but confirmation of these observations is needed.     

Epidemiological Pathology of Dementia: Attributable-Risks at Death in the Medical Research Council Cognitive Function and Ageing Study

Background

Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS).

Methods and Findings

A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%).

Conclusions

Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively “pure,” but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia. Please see later in the article for the Editors'' Summary     

The Stigma of Migraine

Background

People who have a disease often experience stigma, a socially and culturally embedded process through which individuals experience stereotyping, devaluation, and discrimination. Stigma has great impact on quality of life, behavior, and life chances. We do not know whether or not migraine is stigmatizing.

Methods

We studied 123 episodic migraine patients, 123 chronic migraine patients, and 62 epilepsy patients in a clinical setting to investigate the extent to which stigma attaches to migraine, using epilepsy as a comparison. We used the stigma scale for chronic illness, a 24-item questionnaire suitable for studying chronic neurologic diseases, and various disease impact measures.

Results

Patients with chronic migraine had higher scores (54.0±20.2) on the stigma scale for chronic illness than either episodic migraine (41.7±14.8) or epilepsy patients (44.6±16.3) (p<0.001). Subjects with migraine reported greater inability to work than epilepsy subjects. Stigma correlated most strongly with the mental component score of the short form of the medical outcomes health survey (SF-12), then with ability to work and migraine disability score for chronic and episodic migraine and the Liverpool impact on epilepsy scale for epilepsy. Analysis of covariance showed adjusted scores for the stigma scale for chronic illness were similar for chronic migraine (49.3; 95% confidence interval, 46.2 to 52.4) and epilepsy (46.5; 95% confidence interval, 41.6 to 51.6), and lower for episodic migraine (43.7; 95% confidence interval, 40.9 to 46.6). Ability to work was the strongest predictor of stigma as measured by the stigma scale for chronic illness.

Conclusion

In our model, adjusted stigma was similar for chronic migraine and epilepsy, which were greater than for episodic migraine. Stigma correlated most strongly with inability to work, and was greater for chronic migraine than epilepsy or episodic migraine because chronic migraine patients had less ability to work.     

A blood based 12-miRNA signature of Alzheimer disease patients

Background

Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.

Results

We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.

Conclusions

The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.     

Post-Epidemic Chikungunya Disease on Reunion Island: Course of Rheumatic Manifestations and Associated Factors over a 15-Month Period

Although the acute manifestations of Chikungunya virus (CHIKV) illness are well-documented, few data exist about the long-term rheumatic outcomes of CHIKV-infected patients. We undertook between June and September 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed CHIKV disease diagnosed between March 1 and June 30, 2005, were identified through a surveillance database and interviewed by telephone. At the 15-month-period evaluation after diagnosis, 84 of 147 participants (57%) self-reported rheumatic symptoms. Of these 84 patients, 53 (63%) reported permanent trouble while 31 (37%) had recurrent symptoms. Age ≥45 years (OR = 3.9, 95% CI 1.7–9.7), severe initial joint pain (OR = 4.8, 95% CI 1.9–12.1), and presence of underlying osteoarthritis comorbidity (OR = 2.9, 95% CI 1.1–7.4) were predictors of nonrecovery. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition. Three independent risk factors that may aid in early recognition of patients with the highest risk of presenting prolonged CHIKV illness were identified. Such findings may be particularly useful in the development of future prevention and care strategies for this emerging virus infection.     

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study

Objective: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. Design: Prospective case-control study. Setting: National Creutzfeldt-Jakob disease surveillance unit. Subjects: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. Main outcome measure: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. Results: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P=0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P=0.023). Conclusion: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy.

Key messages

• Creutzfeldt-Jakob disease is a rare, fatal neurodegenerative disease. Diagnosis is made clinically and neuropathologically
• There is no serum test which allows the diagnosis to be made while the patient is alive
• In this study raised serum concentrations of S100 protein were found in patients with Creutzfeldt-Jakob disease
• Serum concentrations of S100 could be used with a sensitivity of 77.8% and a specificity of 81.1% to confirm Creutzfeldt-Jakob disease in the differential diagnosis of diseases that cause dementia
• Serial measurement of S100 concentrations will enhance diagnostic accuracy

     

IFNγ Response to Mycobacterium tuberculosis,Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

Objectives

Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development.

Methods

A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination.

Results

Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007).

Discussion

CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.     

Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression

Inherited neurodegenerative diseases, such as Huntington disease and subset of Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis, are caused by the mutant genes that have gained undefined properties that harm cells in the nervous system, causing neurodegeneration and clinical phenotypes. Lowering the mutant gene expression is predicted to slow the disease progression and produce clinical benefit. Administration of small interfering RNA (siRNA) can silence specific genes. However, long term delivery of siRNA to silence the mutant genes, a requirement for treatment of these chronic central nervous system (CNS) diseases, remains a critical unsolved issue. Here we designed and tested a chemically stabilized siRNA against human Cu,Zn-superoxide dismutase (SOD1) in a mouse model for amyotrophic lateral sclerosis. We show that the modified siRNA has enhanced stability and retains siRNA activity. Administration of this siRNA at the disease onset by long term infusion into the CNS resulted in widespread distribution of this siRNA, knocked down the mutant SOD1 expression, slowed the disease progression, and extended the survival. These results bring RNA interference therapy one step closer to its clinical application for treatment of chronic, devastating, and fatal CNS disorders.     

Modeling neurodegenerative disorders in adult somatic cells: A critical review

Development of new therapeutic targets for neurodegenerative disorders has been hampered by a reliance on post mortem tissue that is representative of end-stage disease, or on animal models that fail to provide faithful analogs. However, rapid advances in cellular genetic reprogramming, in particular the induction of somatic cells into stem cells, or directly into neurons, has led to intense interest in modeling of human neurodegeneration in vitro. Here, we critically review current methods and recent progress in cellular models of Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Several challenges are identified, including technical variability, lack of degenerative phenotypes, neurodevelopmental age and establishing ground truths for models of sporadic disease. Recommendations for evaluating neurodegenerative cellular models are proposed along with suggestions for future research.     

Unchanged levels of interleukins, neopterin, interferon-γ and tumor necrosis factor-α in cerebrospinal fluid of patients with dementia of the Alzheimer type

Several histopathological studies suggest that amyloidogenesis in dementia of the Alzheimer type is accompanied by activated glia and glia-derived cytokines, leading to chronic, self-propagating, cytokine-mediated molecular and cellular reactions. As studies regarding inflammatory changes in cerebrospinal fluid of patients with dementia of the Alzheimer type has been inconclusive, we set up a prospective study to assess cerebrospinal fluid levels of interleukin-1β, interleukin-6, interleukin-10, interleukin-12, soluble interleukin-2 receptor, interferon-γ, tumor necrosis factor-α and neopterin in 20 patients with dementia of the Alzheimer type and 20 age- and sex-matched controls. Comparing both groups, no significant differences in concentrations and specific activities could be revealed. An additional 22 patients were included to enlarge the study population. No statistically significant differences were shown comparing patients (n=42) with the control group (n=20). We conclude that the immune-mediated inflammatory changes found in histopathological studies are not reflected in cerebrospinal fluid of patients with dementia of the Alzheimer type. Probably, cytokine production appears very localized in the central nervous system, not allowing representative detection in cerebrospinal fluid.Further studies assessing cytokine levels in various regions of central nervous system of patients with dementia of the Alzheimer type will be of interest to confirm this hypothesis.     

Differences in rapid eye movement sleep behavior disorder manifestation between synucleinopathies and tauopathies

Rapid eye movement sleep behavior disorder (RBD) frequently occurs in synucleinopathies including multiple system atrophy, Parkinson’s disease, and dementia with Lewy bodies despite the clinical course of RBD being different between these disorders. Comparatively, the existence of RBD symptoms is relatively rare in patients with progressive supranuclear palsy, a tauopathy showing atypical parkinsonism compared with Parkinson’s disease. Moreover, in patients with Alzheimer’s disease, which is another tauopathy, RBD symptoms are less frequent than dementia with Lewy bodies, although both disorders share commonalities in terms of the existence of cortical dementia. Thus, RBD is thought to be relatively specific to synucleinopathies.

     

Accuracy of Serological Testing for the Diagnosis of Prevalent Neurocysticercosis in Outpatients with Epilepsy,Eastern Cape Province,South Africa

Background

Few studies have estimated prevalence of neurocysticercosis (NCC) among persons with epilepsy in sub-Saharan Africa. While the limitations of serological testing in identification of NCC are well known, the characteristics of persons who are misdiagnosed based on serology have not been explored. The first objective of this pilot study was to estimate the prevalence of NCC in epilepsy outpatients from an area of South Africa endemic for cysticercosis. The second objective was to estimate the accuracy of serological testing in detecting NCC in these outpatients and characterize sources of disagreement between serology and neuroimaging.

Methodology/Principal Findings

All out-patients aged 5 or older attending the epilepsy clinic of St. Elizabeth''s Hospital in Lusikisiki, Eastern Cape Province, between July 2004 and April 2005 were invited to participate. Epidemiological data were collected by local study staff using a standardized questionnaire. Blood samples were tested by ELISA for antibody and antigen for Taenia solium. Four randomly chosen, consenting participants were transported each week to Mthatha for brain CT scan. The proportion of persons with epilepsy attending St. Elizabeth clinic with CT-confirmed NCC was 37% (95% CI: 27%–48%). Using CT as the gold standard, the sensitivity and specificity of antibody testing for identifying NCC were 54.5% (36.4%–71.9%) and 69.2% (52.4%–83.0%), respectively. Sensitivity improved to 78.6% (49.2%–95.3%) for those with active lesions. Sensitivity and specificity of antigen testing were considerably poorer. Compared to false negatives, true positives more often had active lesions. False positives were more likely to keep pigs and to have seizure onset within the past year than were true negatives.

Conclusions/Significance

The prevalence of NCC in South African outpatients with epilepsy is similar to that observed in other countries where cysticercosis is prevalent. Errors in classification of NCC using serology alone may reflect the natural history of NCC.     

The seeds of neurodegeneration: prion-like spreading in ALS

Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer, Parkinson, and Huntington diseases) can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein's induction of a pathogenic conformation onto its cellular isoform. Evidence for such a prion-like mechanism has now spread to the main misfolded proteins, SOD1 and TDP-43, implicated in amyotrophic lateral sclerosis (ALS). The major neurodegenerative diseases may therefore have mechanistic parallels for non-cell-autonomous spread of disease within the nervous system.     

A Combined CXCL10, CXCL8 and H-FABP Panel for the Staging of Human African Trypanosomiasis Patients

Background

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.

Methods

Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and ≤5 WBC/µL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/µL) patients. The concentration of H-FABP, GSTP-1 and S100β in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1β, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-γ, TNF-α, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.

Results

CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.

Conclusion

This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.     

Autophagy of Mitochondria: A Promising Therapeutic Target for Neurodegenerative Disease

The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neurodegeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. It can be suggested that autophagy dysfunction along with oxidative stress is considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases.     

Community Management of Endemic Scabies in Remote Aboriginal Communities of Northern Australia: Low Treatment Uptake and High Ongoing Acquisition

Background

Scabies and skin infections are endemic in many Australian Aboriginal communities. There is limited evidence for effective models of scabies treatment in high prevalence settings. We aimed to assess the level of treatment uptake amongst clinically diagnosed scabies cases and amongst their household contacts. In addition, we aimed to determine the likelihood of scabies acquisition within these households over the 4 weeks following treatment provision.

Methods and Findings

We conducted an observational study of households in two scabies-endemic Aboriginal communities in northern Australia in which a community-based skin health program was operating. Permethrin treatment was provided for all householders upon identification of scabies within a household during home visit. Households were visited the following day to assess treatment uptake and at 2 and 4 weeks to assess scabies acquisition among susceptible individuals. All 40 households in which a child with scabies was identified agreed to participate in the study. Very low levels of treatment uptake were reported among household contacts of these children (193/440, 44%). Household contacts who themselves had scabies were more likely to use the treatment than those contacts who did not have scabies (OR 2.4, 95%CI 1.1, 5.4), whilst males (OR 0.6, 95%CI 0.42, 0.95) and individuals from high-scabies-burden households (OR 0.2, 95%CI 0.08, 0.77) were less likely to use the treatment. Among 185 susceptible individuals, there were 17 confirmed or probable new diagnoses of scabies recorded in the subsequent 4 weeks (9.2%). The odds of remaining scabies-free was almost 6 times greater among individuals belonging to a household where all people reported treatment uptake (OR 5.9, 95%CI 1.3, 27.2, p = 0.02).

Conclusion

There is an urgent need for a more practical and feasible treatment for community management of endemic scabies. The effectiveness and sustainability of the current scabies program was compromised by poor treatment uptake by household contacts of infested children and high ongoing disease transmission.     

Classification and Clinical Features of Headache Disorders in Pakistan: A Retrospective Review of Clinical Data

Background

Morbidity associated with primary headache disorders is a major public health problem with an overall prevalence of 46%. Tension-type headache and migraine are the two most prevalent causes. However, headache has not been sufficiently studied as a cause of morbidity in the developing world. Literature on prevalence and classification of these disorders in South Asia is scarce. The aim of this study is to describe the classification and clinical features of headache patients who seek medical advice in Pakistan.

Methods and Results

Medical records of 255 consecutive patients who presented to a headache clinic at a tertiary care hospital were reviewed. Demographic details, onset and lifetime duration of illness, pattern of headache, associated features and family history were recorded. International Classification of Headache Disorders version 2 was applied.66% of all patients were women and 81% of them were between 16 and 49 years of age. Migraine was the most common disorder (206 patients) followed by tension-type headache (58 patients), medication-overuse headache (6 patients) and cluster headache (4 patients). Chronic daily headache was seen in 99 patients. Patients with tension-type headache suffered from more frequent episodes of headache than patients with migraine (p<0.001). Duration of each headache episode was higher in women with menstrually related migraine (p = 0.015). Median age at presentation and at onset was lower in patients with migraine who reported a first-degree family history of the disease (p = 0.003 and p<0.001 respectively).

Conclusions/Significance

Patients who seek medical advice for headache in Pakistan are usually in their most productive ages. Migraine and tension-type headache are the most common clinical presentations of headache. Onset of migraine is earlier in patients with first-degree family history. Menstrually related migraine affects women with headache episodes of longer duration than other patients and it warrants special therapeutic consideration. Follow-up studies to describe epidemiology and burden of headache in Pakistan are needed.     

Epilepsy in Onchocerciasis Endemic Areas: Systematic Review and Meta-analysis of Population-Based Surveys

Objective

We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level.

Design

We conducted a systematic review and meta-regression of available data.

Data Sources

Electronic and paper records on subject area ever produced up to February 2008.

Review Methods

We searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models.

Results

Eight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence.

Conclusion

These results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship.