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Biomedical subjects

S Cousens

Publications and source records attributed to S Cousens.

At least 19 recordsLinked to original sources

Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion.

BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by infection with the agent of bovine spongiform encephalopathy (BSE). Epidemiological evidence does not suggest that sporadic CJD is transmitted from person to person via blood transfusion, but this evidence may not apply to vCJD. We aimed to identify whether vCJD is transmissible through blood transfusion. METHODS: The national CJD surveillance unit reported all cases of probable or definite vCJD to the UK blood services, which searched for donation records at blood centres and hospitals. Information on named recipients and donors was provided to the surveillance unit to establish if any matches existed between recipients or donors and the database of cases of vCJD. Recipients were also flagged at the UK Office of National Statistics to establish date and cause of death. FINDINGS: 48 individuals were identified as having received a labile blood component from a total of 15 donors who later became vCJD cases and appeared on the surveillance unit's register. One of these recipients was identified as developing symptoms of vCJD 6.5 years after receiving a transfusion of red cells donated by an individual 3.5 years before the donor developed symptoms of vCJD. INTERPRETATION: Our findings raise the possibility that this infection was transfusion transmitted. Infection in the recipient could have been due to past dietary exposure to the BSE agent. However, the age of the patient was well beyond that of most vCJD cases, and the chance of observing a case of vCJD in a recipient in the absence of transfusion transmitted infection is about 1 in 15000 to 1 in 30000.

Blood Donors↗

Glaucoma case finding: a cluster-randomised intervention trial.

PURPOSE: To assess the effect of an intervention comprising training in optic disc assessment, explicit referral criteria and ophthalmologist feedback on referred patients, on the number of optometrist referrals for suspected glaucoma seen at a referral site and the positive predictive value of those referrals. METHODS: Optometric practices routinely referring to the Ealing Hospital Eye Clinic were randomly divided into two groups taking into consideration those practices, which shared an optometrist (a cluster) and the number of optometrist days worked per week. One group of practices acted as controls, while the other practices were invited to receive the intervention. Data on 397 new patients referred and presenting to Ealing Hospital with suspected glaucoma were collected over a 20-month period. The data on patients who had failed to attend their appointment were collected over 7 months of this period. The number of referrals seen, the positive predictive value of those referrals, and the attendance rate were calculated. Optometrist's opinions of the intervention were assessed qualitatively. Data relating to optometrist compliance with the intervention were also collected. RESULTS: The number of glaucoma referrals presenting to Ealing Hospital from the intervention practices was almost double that from the control practices (210 vs 119). When cluster randomisation, the number of optometrist days per cluster and the number of assessed referrals in the preintervention period are taken into consideration, it is estimated that the intervention is associated with a 52% increase in the number of referrals reaching Ealing Hospital. However, the design effect resulting from the cluster randomisation was unexpectedly high (of the order of 13-14)and so the confidence intervals around the estimate of 52% are very wide (95% c.i. 35% decrease to 253% increase, P = 0.34). There was no evidence of an association between optometrist compliance with the intervention and the number of referrals seen at Ealing Hospital. The positive predictive value (PPV)of referrals was similar for the intervention(0.49 (95% c.i. 0.42, 0.55)) and control groups(0.46 (95% c.i. 0.33, 0.60)). Optometrist opinions of the intervention were largely favourable. All expressed a willingness to participate in future programmes. CONCLUSION: A large difference in the number of referrals between the practice groups was observed. Since the PPV of referral was unchanged, the potential impact of the intervention in terms of numbers of new cases of glaucoma detected in the community is substantial. However, because of its large design effect, this trial does not provide conclusive evidence of an impact of the intervention on referral numbers. A considerably larger trial will be required to produce conclusive evidence of an effect.

Attitude of Health Personnel↗

Sensitivity and specificity of two glaucoma case-finding strategies for optometrists.

Current best practice for primary open-angle glaucoma case-finding comprises history-taking, disc examination, intraocular pressure measurement and suprathreshold visual field analysis (SVFA). An alternative case-finding technique was formulated replacing SVFA with computerised quantitative disc assessment, using the Heidelberg retinal tomograph II (HRT II). Each approach was adopted by four optometrists who screened 29 POAG and 37 normal patients. Average sensitivities and specificities were similar in the two groups [sensitivity 71% (SVFA) vs 69% (HRT II); specificity 94% both groups]. Our inclusion of pre-perimetric glaucoma cases limited the sensitivity of the optometrists in this study. There was evidence to suggest that the optometrists tended to miss early changes at the optic disc such as disc haemorrhage, nerve fibre layer defects and subtle neuroretinal thinning.

Aged↗

Blindness: how to assess numbers and causes?

BACKGROUND: Traditionally, blindness surveys have modelled themselves on the "gold standard" of a census and examination of a whole population. Blindness, however, is a relatively rare condition even in badly affected communities; hence, large sample sizes are required to gain adequate estimates of prevalence, particularly by cause. METHODS: Three assessments of blindness prevalence and aetiology in the same communities are reported. One involved asking individuals questions concerning their visual status during a census (perceived visual status, PVD), one involved examination of all ostensibly visually disabled people presenting to a central point within each community (examination of the visually disabled, EVD), and the final assessment involved a gold standard examination of the whole population (whole community examination, WCE). RESULTS: In a population of 8139 the blindness prevalence was 2.7% PVS, 3.6% EVD, and 3.1% WCE. Attributed causes of blindness were not representative in the PVS except for cataract. The END yielded cause specific estimates not far from those found at WE except for a relative under-representation of glaucoma and optic atrophy. CONCLUSION: Since cataract is, by a significant margin, the most common cause of blindness in the world such a simple method as asking individuals if they are blind and what they believe to be the cause may yield adequate estimates of the problem for planning eye care strategies for this condition. Alternatively, an ophthalmologist visiting villages and examining allcomers for visual disability may provide reasonably accurate cause specific prevalence estimates without the expense of a major blindness survey.

Adolescent↗

Geographical distribution of variant Creutzfeldt-Jakob disease in Great Britain, 1994-2000.

BACKGROUND: Geographical variation in the distribution of variant Creutzfeldt-Jakob disease (vCJD) might indicate the transmission route of the infectious agent to man. We investigated whether regional incidences of vCJD were correlated with regional dietary data. METHODS: The National CJD Surveillance Unit prospectively identified 84 people with vCJD up to Nov 10, 2000, in Great Britain. Their lifetime residential histories were obtained by interviews with a close relative. Cumulative incidences of vCJD by standard region were calculated. Grid references for places of residence in 1991 were identified and evidence of geographical clusters were sought. Data on diet in the 1980s were analysed for regional correlations with vCJD incidence. The socioeconomic status of the places of residence of people with vCJD was compared with that of the general population. FINDINGS: vCJD incidence was higher in the north of Great Britain than the south. The rate ratio (north vs south) was 1.94 (95% CI 1.27-2.98). The mean Carstairs' deprivation score for areas of residence of people with vCJD was -0.09 (-0.73 to 0.55), which is close to the national average of zero. Regional rates of vCJD were correlated with consumption of other meat or meat products as classified and recorded by the Household Food Consumption and Expenditure Survey (r=0.72), but not with data from the Dietary and Nutritional Survey of British Adults. Five people with vCJD in Leicestershire formed a cluster (p=0.004). INTERPRETATION: Regional differences in vCJD incidence are unlikely to be due to ascertainment bias. We had difficulty determining whether regional variations in diet might cause these differences, since the results of dietary analyses were inconsistent.

Adult↗

Intraocular pressure and gonioscopic findings in rural communities mesoendemic and nonendemic for onchoceriasis, Kaduna State, Nigeria.

PURPOSE: To report on glaucoma-related ocular parameters, namely intraocular pressure and peripheral anterior synechiae, in the presence of onchocercal infection. METHODS: Two computer-generated random samples of individuals were drawn from communities mesoendemic and nonendemic for onchocerciasis respectively. Applanation tonometry and gonioscopy were carried out on these individuals. RESULTS: Four hundred and thirty-six and 319 individuals from the mesoendemic and nonendemic communities were examined respectively. The mean intraocular pressure was 1.58 mmHg lower in the individuals from the mesoendemic communities compared with those from the nonendemic communities (p < 0.001) despite the prevalence of peripheral anterior synechiae being higher in the mesoendemic communities. In these communities, there was strong evidence that the prevalence of peripheral anterior synechiae increased with increasing microfilarial load. CONCLUSIONS: Onchocercal infection produces a low-grade inflammatory process, which may result in a lowering of intraocular pressure despite the formation of peripheral anterior synechiae. Glaucomatous optic nerve damage may therefore not be the primary cause of visual loss in ocular onchocerciasis as this occurs late and is probably preceded by other blinding onchocercal pathology.

Adolescent↗

Evidence of behaviour change following a hygiene promotion programme in Burkina Faso.

OBJECTIVES: To determine whether a large, 3-year hygiene promotion programme in Bobo-Dioulasso, Burkina Faso, was effective in changing behaviours associated with the spread of diarrhoeal diseases. The programme was tailored to local customs, targeted specific types of behaviour, built on existing motivation for hygiene, and used locally appropriate channels of communication. METHODS: Two population surveys recorded the coverage of the programme among target audiences (mothers of children aged 0-35 months). Four surveys were carried out: three prior to the programme and one in 1998 (after the programme had been running for 3 years), using structured observation of hygiene behaviours in the participants' homes to document changes in target behaviours. FINDINGS: After the programme had run for 3 years, three-quarters of the mothers targeted had had contact with programme activities. Half could cite the two main messages of the programme correctly. Although the safe disposal of children's stools changed little between 1995 and 1998 (80% pre-intervention, 84% post-intervention), hand-washing with soap after cleaning a child's bottom rose from 13% to 31%. The proportion of mothers who washed their hands with soap after using the latrine increased from 1% to 17%. CONCLUSION: Hygiene promotion programmes can change behaviour and are more likely to be effective if they are built on local research and use locally appropriate channels of communication repeatedly and for an extended time.

Burkina Faso↗

Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma.

OBJECTIVE: To compare the impact of mass treatment with oral azithromycin and topical tetracycline on the prevalence of active trachoma. METHODS: A total of 1803 inhabitants from 106 households of eight Gambian villages were randomized, in pairs, to receive either three doses of azithromycin at weekly intervals, or daily topical tetracycline over 6 weeks. Ocular examinations were conducted before treatment, and 2, 6 and 12 months after treatment. FINDINGS: Prior to treatment, 16% of the study participants had active trachoma. Two months after treatment, the prevalence of trachoma was 4.6% and 5.1% in the azithromycin and the tetracycline groups, respectively (adjusted odds ratio (OR) = 1.09; 95% confidence interval (CI) = 0.53, 2.02). Subsequently, the prevalence rose to 16% in the tetracycline group, while remaining at 7.7% in the azithromycin group (adjusted OR at 12 months = 0.52; 95% CI = 0.34, 0.80). At 12 months post-treatment, there were fewer new prevalent cases in the azithromycin group, and trachoma resolution was significantly better for this group (adjusted OR = 2.02; 95% CI = 1.42, 3.50). CONCLUSION: Oral azithromycin therefore appears to offer a means for controlling blinding trachoma. It is easy to administer and higher coverages may be possible than have been achieved hitherto.

Administration, Oral↗

The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease.

BACKGROUND: There is a need for an accurate non-invasive diagnostic test for variant Creutzfeldt-Jakob disease (vCJD). We investigated the sensitivity and specificity of bilateral pulvinar high signal on magnetic resonance imaging (MRI) for the diagnosis of vCJD. METHODS: MRI from patients with vCJD and controls (patients with suspected CJD) were analysed. Scans were reviewed on two separate occasions by two neuroradiologists and scored for the distribution of changes, and likely final diagnosis. Scans from vCJD cases were reassessed to reach a consensus on all abnormalities. FINDINGS: We analysed 36 patients and 57 controls. vCJD patients were correctly identified based on bilateral pulvinar high signal in 29 of 36 and 32 of 36 cases on the first assessment by the two radiologists, and 32 of 36 and 31 of 36 on their second assessment. Bilateral increased pulvinar signal was identified in one of 57 and one of 57 controls on the first assessment and two of 57 and three of 57 controls on the second assessment. These reported changes in controls were graded as minimal/equivocal in six of seven patients and moderate in one (<0.5% of all control assessments). 80% of the assessments in vCJD cases were graded as moderate or substantial. On consensus review, 28 of 36 cases and none of 57 controls had prominent bilateral pulvinar signal-sensitivity 78% (95% CI 60-90%) and specificity 100% (95% CI 94-100%). Other common MRI features of vCJD were medial thalamic and periaqueductal grey matter high signal, and the notable absence of cerebral atrophy. Pulvinar high signal correlated with histological gliosis. INTERPRETATION: In the appropriate clinical context the MRI identification of bilaterally increased pulvinar signal is a useful non-invasive test for the diagnosis of vCJD.

Adolescent↗

Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects.

OBJECTIVE: To evaluate the rate of brain atrophy calculated from serial magnetic resonance imaging (MRI) registration as a surrogate marker of disease progression for use in clinical trials in Alzheimer disease (AD). METHODS: Eighteen patients with mild to moderate AD and 18 age-matched normal controls underwent 2 MRI brain scans separated by a 12-month interval. Each individual's later scan was registered to their first scan, and the volume of cerebral tissue loss calculated directly from the registered and subtracted MRI scan pairs. The mean and SD of the rate of brain volume changes were used to estimate the sample sizes that would be needed in a clinical trial with a drug anticipated to modify disease progression by varying degrees. Comparable sample size estimates were performed with data for other methods of monitoring rates of brain atrophy, extracted from published papers. RESULTS: The mean (SD) rate of brain atrophy for the patients with AD was 2.37% (1.11%) per year, while in the control group it was 0.41% (0.47%) per year. Based on these figures, to have 90% power to detect a drug effect equivalent to a 20% reduction in the rate of atrophy, 207 patients would be needed in each treatment arm. This assumes a 1-year placebo-controlled trial with a 10% patient dropout rate, and that 10% of scan pairs are unusable. CONCLUSION: Registration of serial MRI volume images provides a powerful method of quantification of brain atrophy that can be used to monitor progression of AD in clinical trials.

Aged↗

Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit.

BACKGROUND: On March 21, 1998, the Regional Health Authority of Bobo-Dioulasso, Burkina Faso, asked the Centre Muraz to investigate an unexplained outbreak of epidemic fatal encephalopathy (EFE). We aimed to identify the cause of this epidemic. METHODS: We identified cases retrospectively through review of health-service records and interviews of family members, village chiefs, and local healers. Active surveillance was started in administrative divisions within the study area in April, 1998, to identify further EFE cases. We did a case-control study of households to investigate the risk from various environmental and health factors. Blood and urine samples were collected if possible and urine dicarboxylic acid concentrations measured by gas chromatography. FINDINGS: 29 cases of EFE were identified from January to May, 1998. Estimated age-specific attack rates (2-6 years) ranged from 31 to 847 per 100,000 population (p<0.001). The most common symptoms were hypotonia, vomiting, convulsions, and coma. All children died in 2-48 h. The only factor associated with EFE was the presence of ackee trees (Blighia sapida) within 100 m of households (odds ratio 5.1 [95% CI 1.8-14.7] p=0.001). Poisoning with unripe ackee fruits was suggested by urine concentrations of dicarboxylic acids four to 200 times higher in cases (n=2) than in controls (n=3). CONCLUSION: Consumption of unripe ackee fruit probably caused this epidemic and may lead to a substantial number of unexplained deaths in preschool children in west Africa every year. Educational campaigns have the potential to prevent these deaths.

Brain Diseases↗

Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent.

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

Animals↗

CD4+ T-lymphocyte counts in HIV infection: are European standards applicable to African patients?

CD4+ lymphocyte count (CD4+ LC) is a widely used marker of Human Immunodeficiency Virus (HIV) immune impairment. Physiological lymphocytosis is frequently encountered in Africans. Therefore, we tried to determine if given CD4+ LC levels are of similar significance in European versus African HIV-infected individuals. Lymphocyte phenotyping of 750 HIV-infected adults was retrospectively analyzed. Three hundred and seventy patients were consecutively selected in Paris, France; 185 in Abidjan, Côte d'Ivoire; and 195 in Bobo-Dioulasso, Burkina Faso. In the three settings, lymphocyte phenotyping was performed by flow cytometry using similar protocols. Data from Abidjan and Bobo-Dioulasso were combined on the basis of geographic proximity and contrasted with those from Paris. Geometric mean levels of Total Lymphocyte Count (TLC), CD4+ LC, CD8+ lymphocyte count (CD8+ LC), and CD4:CD8 ratio, adjusted for percentage of CD4+ T-cells (%CD4+), were compared between Africans and Europeans. For a given %CD4+, TLC and CD4+ LC but not CD8+ LC tended to be about one third higher in West African than in French adults (p < 0.0001). Approximate equivalencies of absolute CD4+ counts in French and West African HIV-infected adults suggest that where thresholds of 200 and 500 CD4+ cells/microliter are applied in Europe, it might be appropriate to apply a threshold of approximately 250 and 700 CD4+ cells/microliter in West Africa, respectively. Establishing indicators of progression of HIV infection with locally appropriate thresholds may represent important steps toward improvement of HIV disease management in Africa.

Adult↗

Measuring hygiene practices: a comparison of questionnaires with direct observations in rural Zaïre.

To date questionnaire surveys have been the most commonly used instruments to measure hygiene behaviours related to water and sanitation. More recently, a number of studies have used structured observations to study practices related to diarrhoea. During a trial of a hygiene education intervention to reduce diarrhoea among young children in Bandundu, Zaire, both instruments were used to measure the disposal of child faeces and various hand-washing practices. Three hundred families were observed and follow-up interviews performed with 274 (91%) mothers. At the individual level, agreement between observed and reported behaviour was little better than might be expected by chance. There was evidence of over-reporting of hand-washing before food preparation (44% vs 33%; P = 0.03), hand-washing before eating (76% vs 60%; P < 0.001) and disposal of the child's faeces in a latrine (75% vs 40%; P < 0.001). On the other hand, hand-washing before feeding the child was reported less often than it was observed (7% vs 64%; P < 0.001). Our data are consistent with the hypothesis that, in general, mothers over-report 'desirable' behaviours. At the same time, our data indicate that open questions may lead to under-reporting of certain behaviours. The repeatability of observations at both the individual and population levels remains to be established.

Adolescent↗

Dirt and diarrhoea: formative research in hygiene promotion programmes.

Investment in the promotion of better hygiene for the prevention of diarrhoeal diseases and as a component of water and sanitation programmes is increasing. Before designing programmes capable of sustainably modifying hygiene behaviour in large populations, valid answers to a number of basic questions concerning the site and the intended beneficiaries have to be obtained. Such questions include 'what practices favour the transmission of enteric pathogens?', 'what advantages will be perceived by those who adopt safe practices?' and 'what channels of communication are currently employed by the target population?' A study of hygiene and diarrhoea in Bobo-Dioulasso, Burkina Faso, used a mixture of methods to address such questions. This paper draws on that experience to propose a plan of preliminary research using a variety of techniques which could be implemented over a period of a few months by planners of hygiene promotion programmes. The techniques discussed include structured observation, focus group discussions and behavioural trials. Modest investment in such systematic formative research with clear and limited goals is likely to be repaid many times over in the increased effectiveness of hygiene promotion programmes.

Adult↗

Visual field constriction as a cause of blindness or visual impairment.

Reported are the results of a study of onchocerciasis in communities mesoendemic for savanna onchocerciasis in Kaduna State, northern Nigeria. The study involved 6831 individuals aged > or = 5 years who underwent an extensive screening examination for visual function including Friedmann field analysis. A total of 185 (2.7%) were bilaterally blind by acuity and an additional 28 (0.4%) were blind by visual field constriction. Also 118 (1.7%) individuals were visually impaired by acuity criteria. No criteria for visual impairment by field constriction have been established, and we therefore investigated three potential criteria. As a result, a further 60 (0.9%) individuals were identified with significant visual impairment due to field loss by the various definitions. Small islands of remaining peripheral field occurred in 50 individuals, while 40 individuals had marked reduction of binocular visual field below the horizontal meridian. Concentric visual field constriction to < 20 degrees was found in seven individuals. The WHO definition of blindness currently includes visual field damage criteria for blindness but not for visual impairment. Visual field loss is recognized as a major disability. We hope that these findings stimulate international discussion leading to the development of satisfactory definitions for visual impairment by visual field constriction.

Adolescent↗

Reactivity and repeatability of hygiene behaviour: structured observations from Burkina Faso.

If interventions promoting improved hygiene behaviour to prevent childhood diarrhoea are to be implemented and evaluated, valid methods for measuring this behaviour will be required. This paper presents findings from a study to investigate the use of structured observations to measure hygiene behaviour in Burkina Faso. Two hundred mothers with young children (2-36 months) were observed on several occasions, with particular attention focused on events/behaviour surrounding defaecation. Child defaecation occurred most often in a potty (67% of occasions). Stools were most often disposed of into a latrine (79%). Following defaecation the child's bottom was usually rinsed using water alone with a bare hand (76%). Subsequent hand washing by the mother/caretaker was much rarer (29%). None of these behaviours appeared "reactive" to the presence of the observer. Less common behaviors showed some evidence of reactivity. The frequency of child defaecation in the yard increased over the course of three observations (5% to 16%; P = 0.01) and the proportion of occasions on which the child was observed to be cleaned after defaecation declined (95% to 85%; P = 0.01). Mothers usually took with them to the latrine a water recipient (91%). Hand washing after leaving the latrine was observed on 30% of occasions. This proportion declined from 36% to 22% over three observations (P = 0.05). Defaecation by older siblings (aged 3-5 years) was usually into a potty (48%) or directly in a latrine (30%). There was no evidence that this behaviour was reactive. The repeatability of behaviours at the individual level was generally low. The site of index child defaecation (kappa = 0.27), how the child's bottom was cleaned (kappa = -0.01) and whether the caretaker washed her hands afterwards (kappa = 0.26) all showed low repeatability. The method of stool disposal was more repeatable (kappa = 0.73). Hand washing by mothers after using the latrine showed moderate repeatability (kappa = 0.40). Older sibling's defaecation behavior had excellent repeatability (kappa = 0.90). Our findings suggest that, in studies which aim to measure behaviour at the population level, structured observations may provide a useful tool. Studies which investigate links between hygiene behaviour and diarrhoea incidence at the individual level will require repeated observations of mothers and children since measuring behaviour during a single observation will lead to misclassification of exposure status, resulting in bias which could mask any underlying association. This is likely to be very costly.

Adult↗

Anaemia among women of reproductive age in Burkina Faso.

The control of anaemia among women of reproductive age (15-49 years) is one of the priorities of the Safe Motherhood initiative. This article presents the results of a study that was carried out to provide some of the information needed for an effective and sustainable programme to control anaemia in women of this age group in Burkina Faso.

Adolescent↗